melphalan and Plasmacytoma

Topics: Animals; Antineoplastic Agents, Alkylating; Cytokines; Growth Substances; Melphalan; Mice; Plasmacytoma; Th1 Cells; Th2 Cells; Tumor Stem Cell Assay

A case of extramedullary plasmacytoma (EMP) of the jejunum, an uncommon neoplasia, is reported. A 56-year-old Japanese woman who experienced intermittent upper abdominal pain and weight loss had a large movable mass in the upper abdomen. The mass was hypervascular in an angiographic study and positive for gallium-67 citrate scintigraphy. Immunoelectrophoresis showed the presence of an M-component of immunoglobulin (Ig) A-lambda in the serum. It was identified as an EMP immunohistochemically positive for IgA-lambda. This M-component disappeared after resection and chemotherapy. The clinical features of this rare neoplastic disorder are discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Immunoglobulin A; Immunoglobulin lambda-Chains; Jejunal Neoplasms; Melphalan; Middle Aged; Paraproteins; Plasmacytoma; Prednisolone

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Drug Therapy, Combination; Female; Fluocortolone; Humans; Mammography; Melphalan; Plasmacytoma; Remission Induction

A 52-year-old woman was admitted to our hospital with the chief complaint of left anterior chest pain. A chest X-ray showed a tumor shadow in the left 4th rib. No abnormalities were detected in peripheral blood and aspirated bone marrow samples. The tumor was surgically resected with the involved bone, the intercostal muscle and the parietal pleura. The resected specimen contained a 3 x 6 x 3 cm lesion, and histological investigation of the tumor revealed a plasmacytoma of the rib. It relapsed as a multiple myeloma within two months after surgery. Chemotherapy was administered and the bone lesions were observed to disappear. We believe that the best way to treat solitary plasmacytoma is to first resect the solitary tumor, and then to add cobalt irradiation and chemotherapy after surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Humans; Melphalan; Middle Aged; Plasmacytoma; Prednisone; Ribs

An extramedullary plasmacytoma (EMP) is presented with an isolated lesion in the urinary bladder accompanying an IgG-K paraproteinemia. After a short-term oral melphalan administration, the tumor soon regressed together with the paraprotein, and has never recurred during the two-year follow-up. This is the fourth case of primary EMP of the urinary bladder reported in the literature.

Topics: Aged; Female; Humans; Melphalan; Plasmacytoma; Urinary Bladder Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow Transplantation; Combined Modality Therapy; Humans; Melphalan; Multiple Myeloma; Myeloma Proteins; Pain; Palliative Care; Plasmacytoma; Prednisone; Prognosis

The extramedullary plasmocytoma is a rare condition accounting for one per cent of malignancies of the upper air way. We present one case of rhinosinusal location, which diagnosis offered some difficulties owing to both the X-ray and clinical findings. Treated with radio- and chemotherapy (without any surgery) the result proved good. In the paper the AA. review and bring up-to-date this pathology.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cobalt Radioisotopes; Combined Modality Therapy; Female; Humans; Maxillary Sinus Neoplasms; Melphalan; Methylprednisolone; Nose Neoplasms; Plasmacytoma; Radioisotope Teletherapy

The authors use data drawn from a wide review of literature with an exhaustive bibliography to confirm the rarity of single plasmocytoma in the cranial vault in comparison to other localizations for this tumour. The case observed well illustrates this conclusion and shows how the patients could survive for a long time because solitary plasmocytoma are so sensitive to radiology.

Topics: Combined Modality Therapy; Humans; Male; Melphalan; Middle Aged; Occipital Bone; Parietal Bone; Plasmacytoma; Prednisone; Radiography; Skull Neoplasms

Topics: Alkylating Agents; Amyloidosis; Anemia; Anemia, Refractory; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Blood Transfusion; Bone and Bones; Bone Marrow Examination; Bone Marrow Transplantation; Bone Neoplasms; Calcium; Combined Modality Therapy; Diagnosis, Differential; Heavy Chain Disease; Humans; Immunoglobulin D; Immunotherapy; Interferons; Kidney Failure, Chronic; Leukemia; Melphalan; Mice; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Myeloma Proteins; Osteolysis; Osteosclerosis; Paraproteinemias; Plasma Cells; Plasmacytoma; Prednisone; Radionuclide Imaging; Waldenstrom Macroglobulinemia

A 61-year-old man with a primary thyroid plasmacytoma was studied. Intracytoplasmic monoclonal immunoglobulin (IgG-kappa) was demonstrated in tissue sections, using the immunoperoxidase technique. After histologic diagnosis of plasmacytoma, serum immunoelectrophoresis revealed a monoclonal component (IgG-kappa). Roentgenographic skeletal survey and bone marrow examination gave normal results. The patient received postoperative therapy with radiation and drugs. As of this writing, he is alive 20 months after diagnosis, without evidence of tumor.

Topics: Adult; Aged; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Immunoenzyme Techniques; Immunoglobulin G; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisone; Thyroid Neoplasms; Thyroidectomy; Thyroiditis

Topics: Anemia; Blood Protein Electrophoresis; Blood Transfusion; Blood Viscosity; Chlorambucil; Drug Therapy, Combination; Humans; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisolone; Waldenstrom Macroglobulinemia

Topics: Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Humans; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Plasmacytoma; Procarbazine; Waldenstrom Macroglobulinemia

Topics: Bence Jones Protein; Blood Protein Electrophoresis; Bone Marrow Cells; Cell Count; Clone Cells; Cyclophosphamide; DNA; gamma-Globulins; Humans; Immunoglobulin G; Immunoglobulins; Leukemia, Myeloid; Melphalan; Middle Aged; Multiple Myeloma; Mutation; Plasmacytoma; Ribosomes

Topics: Aged; Diagnosis, Differential; Female; gamma-Globulins; Humans; Male; Melphalan; Middle Aged; Plasmacytoma

Topics: Allopurinol; Androstanes; Antineoplastic Agents; Blood Proteins; Cyclophosphamide; Follow-Up Studies; Glucocorticoids; Humans; Melphalan; Plasmacytoma; Prednisone; Proteinuria

Topics: Antineoplastic Agents; Cyclophosphamide; Melphalan; Plasmacytoma; Urethane

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome is a rare multisystem disorder. Overproduction of vascular endothelial growth factor (VEGF) by plasmocytoma could be responsible for the symptoms. The authors treated four patients with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Within 6 months, symptoms associated with rapid normalization of serum VEGF levels improved.

Topics: Adult; Aged; Down-Regulation; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Peripheral Nervous System Diseases; Plasmacytoma; POEMS Syndrome; Transplantation, Autologous; Treatment Outcome; Vascular Endothelial Growth Factor A

Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p < 0.01). Treatment was well tolerated; planned doses were administered in all cases; no delays in treatment or acute side-effects were observed during treatment. Long-term secondary toxicities including secondary neoplasms and acute leukaemia, have not been observed. We felt that the use of adjuvant chemotherapy after adequate doses of radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Female; Humans; Life Tables; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmacytoma; Prednisone; Prospective Studies; Remission Induction; Survival Analysis; Treatment Outcome

8 patients with plasmocytomas were treated with Endoxan and compared with 5 patients without any considerable treatment. Diagnosis, therapy and prognosis of plasmocytoma are discussed. Particularly mentioned are 3 patients with secondary tumours during cytostatic treatment, a plasmocytoma without paraprotein, a tumorous plasmocytoma with double paraproteinemia and a gammopathia with further development into a plasmocytoma 10 years later.

Topics: Aged; Alkylating Agents; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Hypergammaglobulinemia; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Male; Melphalan; Middle Aged; Plasmacytoma; Prognosis

The results of chemotherapy in 24 patients with extramedullary plasmacytoma are reported. Complete regressions, including disappearance of monoclonal paraprotein and healing of bone lesions, were seen in 12 of 20 (60%) patients with disseminated disease. Extramedullary plasmacytoma responds better to chemotherapy than myeloma, and treatment should be pursued with vigour until all signs of disease have disappeared. Sensitivity to single-agent chemotherapy may vary, and if treatment fails with one agent, others should be tried.

Topics: Adult; Aged; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Plasmacytoma; Prednisone; Radiography

Twenty-eight patients with multiple myeloma have been treated with a quadruple chemotherapeutic regimen consisting of 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone. Nineteen new patients and nine who had escaped from previous single-agent therapy were included in the study. The results to date, on eight criteria of response, seem to be superior to those obtained from previous chemotherapeutic regimens. The study has been in progress for 18 months and only three patients have died. Only one who had not received previous therapy died, and she had complicating hyperparathyroidism, which almost certainly contributed to her death.

Topics: Bone Marrow Examination; Calcium; Carmustine; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Hemoglobins; Humans; Immunoglobulin Fragments; Immunoglobulins; Kidney Function Tests; Melphalan; Multiple Myeloma; Myeloma Proteins; Plasmacytoma; Prednisolone; Serum Albumin

Topics: Clinical Trials as Topic; Humans; Immunoglobulins; Melphalan; Plasmacytoma; Prednisolone; Prednisone; Time Factors

Topics: Bence Jones Protein; Blood Cell Count; Blood Platelets; Blood Protein Electrophoresis; Blood Proteins; Bone Marrow; Bone Marrow Cells; Clinical Trials as Topic; Follow-Up Studies; Hemoglobins; Humans; Leukocytes; Melphalan; Multiple Myeloma; Plasmacytoma; Staining and Labeling

A 71-year-old woman diagnosed with type II diabetes mellitus with severe iron deficiency anemia and positive fecal occult blood. Colonoscopy was performed, showing a soft mass in the ascending colon, with biopsies compatible with plasmacytoma and restriction for Kappa light chains. After bone marrow aspiration, associated IgG multiple myeloma was detected, so chemotherapy with VMP (bortezomib, melphalan and prednisone) was started. Colonoscopy six months later showed that the ulcerated lesion had a reduction in tumor size of up to 80%. A 27-year-old male with a history of kidney transplantation and symptoms of chronic diarrhea, colonoscopy was indicated with the finding of a large exophytic and ulcerated lesion in the cecum. Pathology revealed plasmacytoma with restriction of lambda light chains. After ruling out lesions in other locations, the patient was treated with immunochemotherapy according to the Bortezomib-Rituximab-Dexamethasone scheme, with subsequent complete clinical and endoscopic remission. Plasmacytoma accounts for < 4 % of plasma cell tumours. It may appear isolated or associated with another plasma cell neoplasm, mainly multiple myeloma. Its presence in the gastrointestinal tract is rare, being infrequent in the stomach or small intestine, and even rarer in the colonic tract (incidence 1/10,000,000). The clinical manifestations are similar to those of other colon neoplasms, while the treatment or prognosis may differ from those of other neoplasms. In patients with clinical suspicion, it is important to perform an early endoscopic study, especially in patients diagnosed with multiple myeloma.

Topics: Adult; Aged; Bortezomib; Dexamethasone; Diabetes Mellitus, Type 2; Female; Humans; Immunoglobulin G; Male; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisone; Rituximab; Tertiary Care Centers

We report a case of a relapsed hemophagocytic intramedullary plasmacytoma, previously non-phagocytic, in conjunction with development of a new clone with different cytogenetic abnormalities forming a solitary plasmacytoma.

Topics: Adult; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Bortezomib; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Female; Humans; Magnetic Resonance Imaging; Melphalan; Neoplasm Recurrence, Local; Oligopeptides; Plasmacytoma; Positron Emission Tomography Computed Tomography; Pubic Bone; Rare Diseases; Stem Cell Transplantation; Thalidomide; Transplantation, Autologous; Treatment Outcome

Cutaneous plasmacytosis (CP) is a syndrome of multiple cutaneous plasma cell tumors, in the absence of multiple myeloma. Although rare in both humans and dogs, treatment recommendations are usually extrapolated from multiple myeloma protocols. To date, no case series of CP have been described in the veterinary literature.. To describe clinical presentation, determine treatment response rates and duration, and report overall survival of dogs with CP.. Twenty-one client-owned dogs with CP.. Medical records of 21 dogs with CP were reviewed. Diagnosis was based on histopathologic evaluation of at least 1 representative cutaneous or subcutaneous lesion in dogs with ≥3 lesions. Dogs with suspicion of multiple myeloma were excluded.. The most commonly affected breeds were the golden (5/21) and Labrador retriever (3/21). Fourteen of 21 dogs had >10 lesions, with some having >100. Lesions commonly were described as round, raised, pink-to-red, and variably alopecic or ulcerated. The most commonly used drug protocol was combined melphalan and prednisone, with an overall response rate (ORR) of 73.7% (14/19 dogs). Single-agent lomustine was associated with a similar ORR of 71.4% (5/7 dogs). For all treatments combined, the median progression-free interval after the first treatment was 153 days. The median survival time from the first treatment was 542 days.. Alkylating agents were effective in inducing remission of CP; corticosteroids, melphalan, and lomustine were the most commonly used drugs. Survival times were similar to those reported in dogs with multiple myeloma treated with alkylating agents.

Topics: Animals; Antineoplastic Agents, Alkylating; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Lomustine; Male; Melphalan; Plasmacytoma; Prednisone; Skin; Skin Neoplasms

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Mediastinal Neoplasms; Mediastinoscopy; Melphalan; Plasmacytoma; Prednisone; Thalidomide; Tomography; Treatment Outcome

Plasmacytomas could involve any organ, and at times might pose a diagnostic challenge when the site of involvement is unusual, or if the presentation is similar to other diseases. We describe a 48-year-old man presenting with worsening shortness of breath and chest discomfort with radiologic evidence of mediastinal enlargement, mimicking a lymphoma with mediastinal involvement. An excisional biopsy of a mediastinal lymph node showed a plasma-cell infiltrate strongly positive for CD138, with a flow-cytometry analysis showing a population of lambda-restricted neoplastic plasma cells. He failed to respond to 50Gy involved-field radiotherapy, but achieved a partial response to combination chemotherapy. He underwent high-dose chemotherapy with melphalan (200mg/m(2)) followed by lenalidomide maintenance, and is in complete remission 18months postautografting. This case illustrates a unique and rare presentation of primary lymph-node plasmacytomas involving the mediastinum potentially mistaken as lymphoid malignancy. Clinicians should be aware of the plasma-cell origin of the mediastinal neoplastic process.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Alkylating; Humans; Lenalidomide; Lymph Nodes; Male; Mediastinal Neoplasms; Mediastinum; Melphalan; Middle Aged; Plasma Cells; Plasmacytoma; Syndecan-1; Thalidomide

The gross majority of extramedullary plasmacytomas arise in the lymphatic tissue of the upper respiratory tract. On average, one third of patients with a solid plasmacytoma will develop multiple myeloma, resulting in a worse clinical outcome. We describe a case of rapid recurrent extramedullary plasmacytomas in the background of an asymptomatic multiple myeloma.. A 71-year-old, white Caucasian woman presented with three extramedullary plasmacytomas occurring within a short time period. The third plasmacytoma was accompanied by progressive cervical pain and swallow dysfunction. Additional immunostaining test results were negative for CD56 and showed high MIB-1 expression in the extramedullary plasmacytoma and low MIB-1 expression in the bone marrow. A conventional swallow X-ray did not show any obstruction, however a magnetic resonance imaging scan of her cervical backbone revealed an extramedullary plasmacytoma, threatening her spinal cord. A short course of radiation therapy alleviated her pain and during almost a two-year follow-up period, the multiple myeloma remained asymptomatic, despite the rise in immunoglobulin A lambda levels. After the appearance of the third plasmacytoma, systemic chemotherapy was started to prevent the development of a fourth plasmacytoma, despite the asymptomatic character of the multiple myeloma.. In this case report we describe the rapid appearance of extramedullary plasmacytomas in the background of an asymptomatic multiple myeloma. An immunohistochemical analysis was negative for CD56 and showed high MIB-1 expression in the extramedullary plasmacytoma and low MIB-1 expression in the bone marrow, contributing to the potential underlying pathophysiology of the recurrent extramedullary plasmacytomas and their genetic changes. Systemic chemotherapy was started and no fourth extramedullary plasmacytoma has developed since.

Topics: Aged; Antineoplastic Agents; Combined Modality Therapy; Female; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Melphalan; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Plasmacytoma; Prednisone

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cesarean Section; Chemoradiotherapy; Cisplatin; Combined Modality Therapy; Contraindications; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Fatal Outcome; Female; Hematopoietic Stem Cell Transplantation; Humans; Hypercalcemia; Idarubicin; Infant, Newborn; Lenalidomide; Male; Melphalan; Methylprednisolone; Multiple Myeloma; Myeloma Proteins; Osteolysis; Plasmacytoma; Postpartum Period; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Pyrazines; Remission Induction; Spinal Cord Compression; Thalidomide; Thoracic Vertebrae; Transplantation, Autologous

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) ± surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P = 0.2). The 5- and 10-year MM-free survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P = 0.054). Overall, the 5- and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Boronic Acids; Bortezomib; Chemotherapy, Adjuvant; Dexamethasone; Disease Progression; Female; Greece; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Multivariate Analysis; Neoplasm Recurrence, Local; Plasmacytoma; Prognosis; Pyrazines; Remission Induction; Retrospective Studies; Survival Analysis; Treatment Outcome

We report a 48-year-old man, a farmer, presenting with chronic sensori-motor polyneuropathy. Electrophysiology revealed demyelinating type of neuropathy. Immunoelectrophoresis for monoclonal protein was negative; however, plasmacytoma was discovered on spine imaging. After receiving radiotherapy and chemotherapy over past 9 months there has been a considerable improvement in patient's disability. This case highlights the role of skeletal survey in evaluation of chronic demyelinating neuropathy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; POEMS Syndrome; Radiography; Spinal Neoplasms

Recent reports indicate that in vitro drug screens combined with gene expression profiles (GEP) of cancer cell lines may generate informative signatures predicting the clinical outcome of chemotherapy. In multiple myeloma (MM) a range of new drugs have been introduced and now challenge conventional therapy including high dose melphalan. Consequently, the generation of predictive signatures for response to melphalan may have a clinical impact. The hypothesis is that melphalan screens and GEPs of B-cell cancer cell lines combined with multivariate statistics may provide predictive clinical information.. Microarray based GEPs and a melphalan growth inhibition screen of 59 cancer cell lines were downloaded from the National Cancer Institute database. Equivalent data were generated for 18 B-cell cancer cell lines. Linear discriminant analyses (LDA), sparse partial least squares (SPLS) and pairwise comparisons of cell line data were used to build resistance signatures from both cell line panels. A melphalan resistance index was defined and estimated for each MM patient in a publicly available clinical data set and evaluated retrospectively by Cox proportional hazards and Kaplan-Meier survival analysis.. Both cell line panels performed well with respect to internal validation of the SPLS approach but only the B-cell panel was able to predict a significantly higher risk of relapse and death with increasing resistance index in the clinical data sets. The most sensitive and resistant cell lines, MOLP-2 and RPMI-8226 LR5, respectively, had high leverage, which suggests their differentially expressed genes to possess important predictive value.. The present study presents a melphalan resistance index generated by analysis of a B-cell panel of cancer cell lines. However, the resistance index needs to be functionally validated and correlated to known MM biomarkers in independent data sets in order to better understand the mechanism underlying the preparedness to melphalan resistance.

Topics: Antineoplastic Agents; B-Lymphocytes; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Least-Squares Analysis; Lymphoma, Large B-Cell, Diffuse; Melphalan; Multiple Myeloma; Oligonucleotide Array Sequence Analysis; Plasmacytoma

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Biopsy, Needle; Bone Marrow; Bone Marrow Neoplasms; Drug Therapy, Combination; Humans; Immunoelectrophoresis; Male; Melphalan; Plasmacytoma; Prednisone; Rib Fractures; Stem Cell Transplantation

Topics: Acute Kidney Injury; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Humans; Kidney Neoplasms; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Plasma Cells; Plasmacytoma; Prednisolone; Thalidomide; Urine

We report the case of a 68 year-old man in whom a tumour of the colon was identified by colonoscopy, during diagnostic studies for lower gastrointestinal bleeding as an outpatient. Histological examination showed clonal proliferation of plasma cells IgG-K. No other location was affected (including bone marrow). Diagnosis of plasmacytoma of the colon was made. We have carried out a review of the literature in relation to this unusual disorder.

Topics: Adrenal Cortex Hormones; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonoscopy; Combined Modality Therapy; Diverticulum; Fatal Outcome; Gastrointestinal Hemorrhage; Hemorrhoids; Humans; Lymphatic Metastasis; Male; Melphalan; Neoplasm Recurrence, Local; Plasmacytoma; Rectum; Sigmoid Neoplasms

Solitary plasmacytoma (SP) of the bone is a rare plasma-cell neoplasm. There are no conclusive data in the literature on the optimal radiation therapy (RT) dose in SP. Therefore, in this large retrospective study, we wanted to assess the outcome, prognostic factors, and the optimal RT dose in patients with SP.. Data from 206 patients with bone SP without evidence of multiple myeloma (MM) were collected. Histopathological diagnosis was obtained for all patients. The majority (n = 169) of the patients received RT alone; 32 chemotherapy and RT, and 5 surgery. Median follow-up was 54 months (7-245).. Five-year overall survival, disease-free survival (DFS), and local control was 70%, 46%, and 88%; respectively. Median time to MM development was 21 months (2-135) with a 5-year probability of 51%. In multivariate analyses, favorable factors were younger age and tumor size < 5 cm for survival; younger age for DFS; anatomic localization (vertebra vs. other) for local control. Older age was the only predictor for MM. There was no dose-response relationship for doses 30 Gy or higher, even for larger tumors.. Younger patients, especially those with vertebral localization have the best outcome when treated with moderate-dose RT. Progression to MM remains the main problem. Further investigation should focus on adjuvant chemotherapy and/or novel therapeutic agents.

Topics: Actuarial Analysis; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Cohort Studies; Combined Modality Therapy; Dexamethasone; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Radiation; Doxorubicin; Europe; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; North America; Plasmacytoma; Prednisone; Prognosis; Proportional Hazards Models; Radiotherapy Dosage; Retrospective Studies; Spinal Neoplasms; Treatment Outcome; Vincristine

A 68-year-old woman suffering from a left iliac tumor and severe back pain was admitted to another hospital in May 1999. The bone X-ray, CT scan and MRI demonstrated a 7 cm x 5 cm left iliac tumor with osteolysis and she was transferred to our hospital. Angiography demonstrated multiple hypervascular lesions in the left ilium, lumbar vertebrae, left ischium, left pubis and left rib. The tumor was resected and diagnosed as a plasmacytoma. Immunoelectrophoresis did not show any M-protein in the serum and urine, but the patient was diagnosed as having a non-secretory or low producing multiple myeloma because of the presence of 42.8% of abnormal plasma cells in the bone marrow aspirate. Her symptoms improved following 3 courses of MCNU-VMP therapy and the bone marrow plasma cells decreased to less than 5%. She was discharged and treated as an outpatient but relapsed and died of chemotherapy-resistant myeloma. We report this case because macro-angiogenesis in a multiple myeloma demonstrated by angiography is rare and interesting.

Topics: Aged; Angiography; Antineoplastic Combined Chemotherapy Protocols; Bone and Bones; Drug Administration Schedule; Female; Humans; Melphalan; Multiple Myeloma; Neovascularization, Pathologic; Nitrosourea Compounds; Plasmacytoma; Prednisolone; Prednisone; Tomography, X-Ray Computed; Vindesine

A 52-year-old patient with atypical plasmocytoma presented with a bilateral serous detachment of the retina as well as a huge detachment of the pigment epithelium (PE) in the periphery. Shortly thereafter the PE ruptured. In the left eye this led to substantial central macular fibrosis.. The clinically healthy patient showed a nephrotic syndrome; neither typical monoclonality was detectable nor was erythropoiesis or myelopoiesis reduced.. To avoid further reduction of VA pars plana vitrectomy (ppV) with silicone oil tamponade and laser coagulation was performed. Clinical findings were reduced significantly and VA was stabilized for 2.5 years.. PE detachments and serous retinal detachments in patients with nephrotic syndrome are only mentioned in a few cases. However, a peripheral rupture of the PE to this extent seems to be very rare. Early ppV with silicone oil and laser coagulation may prevent further macular fibrosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Choroidal Neovascularization; Comorbidity; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Kidney Neoplasms; Laser Coagulation; Lenses, Intraocular; Melphalan; Middle Aged; Nephrotic Syndrome; Ophthalmoscopy; Plasmacytoma; Postoperative Complications; Prednisolone; Recurrence; Renal Insufficiency; Reoperation; Retinal Detachment; Retinal Perforations; Silicone Oils; Visual Acuity; Vitrectomy

Topics: Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Humans; Liver Neoplasms; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisolone; Splenic Neoplasms; Tomography, X-Ray Computed

Plasmacytoma is an uncommon tumor and is rarely encountered as a primary pulmonary neoplasm. Herein we describe the conventional radiographic and computed tomographic findings in a patient with a primary pulmonary plasmacytoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bronchoscopy; Cyclophosphamide; Female; Hemoptysis; Humans; Immunoenzyme Techniques; Lung; Lung Neoplasms; Melphalan; Middle Aged; Plasmacytoma; Prednisone; Remission Induction; Tomography, X-Ray Computed

Although autologous stem cell transplantation (ASCT) is considered standard treatment in patients with multiple myeloma (MM), limited experience is available on this approach in patients with plasmacytoma (PC). Twelve patients with high-risk PC received ASCT in Finland 1994-2002. There were nine males and three females with a median age of 50 yr (32-64). Ten patients had a PC of bone, whereas two patients had extramedullary PCs. The median time from the diagnosis to ASCT was 9 months (5-100). At the time of ASCT six patients were in first complete remission (CR) or partial remission (PR), in four patients the disease was refractory to the first line therapy and two patients had relapsed. High-dose therapy consisted of melphalan (MEL)200 (n = 7), MEL200 x 2 (n = 3) or total body irradiation (TBI)-MEL140 (n = 2). No transplant-related deaths occurred. After ASCT eight patients (67%) were in CR, one patient in very good PR and one patient in PR; two patients were non-responders. With a median follow-up of 48 months from ASCT, 11 patients (92%) are alive. Six patients (50%) have relapsed or progressed 3-81 months from ASCT. ASCT is feasible in this patient population resulting in promising overall survival. A randomised trial is needed to assess the real value of ASCT when compared with other treatment options in patients with high-risk PC.

Topics: Adult; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Female; Finland; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Retrospective Studies; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous; Whole-Body Irradiation

We have recently reported, in a murine tumor model, that apoptotic cells induced by different agents may vary in their ability to elicit host immunity. The basis for this observation is unclear but may involve varying efficiencies of cross-presentation and/or direct activation of immunity by different apoptotic preparations. As a first step in addressing this issue, we compared expression patterns of selected immune genes (MHC class I, class II, CD40, B7-1, B7-2) on viable and apoptotic populations induced by four different agents. The histone deacetylase inhibitor trichostatin A (TSA) induced MHC class II expression on viable and apoptotic cell populations, while LPAM, H2O2 and gamma-irradiation did not activate class II. Each agent employed elicited a different expression pattern of costimulatory molecules (CD40, B7-1, B7-2) on both apoptotic and 7-AAD+ 'necrotic' populations. In striking contrast to the TSA induction of MHC class II, class I cell surface protein was diminished on the apoptotic populations. These effects were not a result of changes in the cell cycle produced by the various treatments. The data demonstrate that distinctive gene expression patterns on viable and apoptotic cells are elicited by different apoptosis inducing agents. We discuss how expression patterns on dead or dying tumor cells could potentially affect the tumor's ability to elicit immunity.

Topics: Animals; Antigens, CD; Antineoplastic Agents, Alkylating; Apoptosis; B7-1 Antigen; B7-2 Antigen; CD40 Antigens; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Genes, MHC Class I; Genes, MHC Class II; Histone Deacetylase Inhibitors; Hydroxamic Acids; Melphalan; Membrane Glycoproteins; Mice; Necrosis; Plasmacytoma

Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiac Tamponade; Cyclophosphamide; Female; Heart Neoplasms; Humans; Melphalan; Middle Aged; Plasmacytoma; Prednisolone; Prednisone; Vincristine

In this study, we show that engagement of CTLA-4 on tumor-infiltrating lymphocytes from low-dose melphalan (L-phenylalanine mustard (L-PAM))-treated MOPC-315 tumor bearers led to IL-10 secretion. In addition, the inhibitory activity of CTLA-4 ligation for IFN-gamma secretion following stimulation with anti-CD3 plus anti-CD28 mAb depended on IL-10 production. Consistent with the importance of IL-10 for CTLA-4-mediated inhibition, administration of neutralizing anti-IL-10 mAb to low-dose L-PAM-treated MOPC-315 tumor bearers (administration of blocking anti-CTLA-4 mAb) resulted in enhanced tumor-infiltrating lymphocyte-mediated anti-MOPC-315 cytotoxicity and led to complete tumor eradication in a higher percentage of mice than that observed with low-dose L-PAM alone. The percentage of MOPC-315 tumor-bearing mice cured following administration of neutralizing anti-IL-10 mAb to low-dose L-PAM-treated MOPC-315 tumor bearers was comparable to that observed following administration of blocking anti-CTLA-4 mAb. Moreover, IL-10 neutralization together with CTLA-4 blockade did not provide added therapeutic benefits to low-dose L-PAM-treated MOPC-315 tumor bearers. Taken together, these results indicate that CTLA-4 blockade improves the therapeutic outcome of low-dose L-PAM for MOPC-315 tumor bearers by inhibiting IL-10 secretion as a consequence of blocking CTLA-4 ligation.

Topics: Animals; Antibodies, Blocking; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Cell Line, Tumor; CTLA-4 Antigen; Dose-Response Relationship, Immunologic; Down-Regulation; Immunosuppressive Agents; Interferon-gamma; Interleukin-10; Lymphocytes, Tumor-Infiltrating; Melphalan; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Transplantation; Plasmacytoma; T-Lymphocytes, Cytotoxic; Up-Regulation

An 8-year-old female Shetland sheep dog had hyperproteinemia with a monoclonal gammopathy and a solid mass on the liver, which was histologically diagnosed as a plasma cell tumor. After the treatment of surgery and chemotherapy, serum protein level reduced to the normal range and the gammopathy was disappeared. These findings indicate the plasma cell tumor developed primarily from the liver.

Topics: Animals; Dog Diseases; Dogs; Liver; Liver Neoplasms; Melphalan; Paraproteinemias; Plasmacytoma; Prednisolone

Topics: Aged; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Humans; Immunoglobulin A; Immunoglobulin kappa-Chains; Male; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisolone; Skin Neoplasms

Nodular regenerative hyperplasia (NRH) of the liver is an infrequent entity that is usually diagnosed after the appearance of clinical signs of portal hypertension such as hepatomegaly, splenomegaly or upper gastrointestinal bleeding due to esophageal varices, which are the most frequently found clinical manifestations in NRH. Ascites is a less frequent finding and has always been described in association with other manifestations of portal hypertension. We describe a new case of NRH with atypical presentation in which ascites was the sole clinical manifestation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Bronchopneumonia; Combined Modality Therapy; Disease Progression; Fatal Outcome; Focal Nodular Hyperplasia; Humans; Hypertension, Portal; Liver Regeneration; Lumbar Vertebrae; Male; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisone; Spinal Neoplasms

An 8-year-old, castrated male Domestic Short-haired cat was referred for evaluation of a possible intraocular neoplasm following previous ocular trauma. The eye was blind, and uveitis and an iridal mass were noted on examination. An enucleation was performed and the mandibular lymph node excised. Histopathologic examination revealed neoplastic proliferation of plasma cells in the iris and lymph node. No other evidence of disseminated disease was detected. This is the first case reported of an intraocular extramedullary plasmacytoma in the cat. The variation in clinical manifestations and potential association with multiple myeloma are not known at this time. Disseminated metastasis from a primary plasmacytoma of the uveal tract could also involve the bone marrow and be indistinguishable from multiple myeloma. Early enucleation, as in trauma-associated sarcomas, may be indicated to prevent metastasis. Periodic systemic evaluation for evidence of multiple myeloma should be performed.

Topics: Animals; Antineoplastic Agents; Blindness; Cat Diseases; Cats; Drug Therapy, Combination; Eye Injuries; Eye Neoplasms; Lymphatic Metastasis; Male; Melphalan; Orbit Evisceration; Plasmacytoma; Prednisone

A 34-year-old man was diagnosed as having solitary testicular plasmacytoma. He had received palliative radiotherapy, several combined chemotherapies including CHOP chemotherapy (vincristine, cyclophosphamide, Adriamycin, and prednisone), MP (melphalan and prednisone) and M-2 protocol (melphalan, prednisone, vincristine, carmustine, and cyclophosphamide), and interferon therapy as 3 million units subcutaneous injection three times a week for 1 year. Extensive bone plasmacytoma developed 7 years later without bone marrow involvement. We suggest that early use of combined chemoradiotherapy and high-dose chemotherapy with autologous stem cell support should be investigated in patients with testicular plasmacytoma with dissemination.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Male; Melphalan; Plasma Cells; Plasmacytoma; Prednisone; Skull Neoplasms; Testicular Neoplasms; Tomography, X-Ray Computed; Vincristine

Liver plasmacytoma is a very rare form of solitary plasmacytoma, in fact the presence of plasma cells in the liver is generally associated with a more aggressive form of multiple myeloma. We report an unusual case of liver plasmacytoma without systemic disease, diagnosed by percutaneous needle biopsy of the hepatic lesion, treated with six courses of melphalan and prednisone who achieved a good clinical remission after five years of follow-up.

Topics: Aged; Antineoplastic Agents; Follow-Up Studies; Humans; Liver Neoplasms; Male; Melphalan; Plasmacytoma; Prednisone; Time Factors; Treatment Outcome

We report three cases of massive chest wall plasmacytoma, each greater than 10 cm in diameter, without evidence of overt myeloma, whom we treated with a combination of VAD chemotherapy consolidated by high-dose melphalan and autologous peripheral blood stem cell transplantation and radical radiotherapy. All three patients completed all components of their therapy without experiencing any major side effects and one patient has had a durable remission. The other two patients have had disease progression but at sites other than the original tumour.

Topics: Antineoplastic Agents, Alkylating; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Remission Induction; Soft Tissue Neoplasms; Thoracic Wall

Solitary plasmacytomas include extramedullary plasmacytomas and those found in the bone. Seventy percent of patients are male and the median age is 50-55 years, younger than that for plasma cell myeloma. Most solitary plasmacytomas of bone eventually evolve to plasma cell myeloma within 2-10 years, while the extramedullary ones do so infrequently. We present an unusual case of intra-abdominal plasmacytoma in a young woman which was misdiagnosed and treated as T cell lymphoma initially. Typical manifestations of plasma cell myeloma appeared one year later. High dose chemotherapy followed by allogeneic peripheral stem cell blood transplantation (allo-PBSCT) was given. Relapse in skin occurred one year after allo-PBSCT, and was treated with wide excision and local irradiation. The patient was well and alive without evidence of disease 4 years after wide excision of the recurrence of chest wall solitary plasmacytoma and local radiotherapy.

Topics: Abdominal Neoplasms; Adult; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisolone; Transplantation, Homologous

We have previously shown that administration of a low-dose of melphalan (L-phenylalanine mustard; L-PAM) to mice bearing a large s.c. MOPC-315 tumor leads to up-regulation of TNF-alpha expression, which is first evident at the mRNA level at 24 h after the chemotherapy. In this study, we show accumulation of IFN-beta mRNA in the spleen and tumor nodule of such mice as early as 1 h after the chemotherapy followed by elevated production of IFN-beta protein. IFN-beta protein in turn was found to be important for the L-PAM-induced up-regulation of TNF-alpha expression, as neutralization of IFN-beta inhibited the L-PAM-induced up-regulation of TNF-alpha mRNA expression in MOPC-315 tumor cells. In addition, L-PAM failed to up-regulate TNF-alpha expression in spleen cells from mice in which signaling by IFN-beta is deficient. Studies into the mechanism through which L-PAM leads to rapid accumulation of IFN-beta mRNA revealed that it requires de novo RNA synthesis, indicating that the regulation is at the transcriptional level. However, it did not require de novo protein synthesis, indicating that activation of pre-existing transcription factors is sufficient for IFN-beta gene expression. The L-PAM-induced accumulation of IFN-beta mRNA was mimicked with H(2)O(2) and was prevented with the antioxidant N-acetyl-L-cysteine, indicating that reactive oxygen species are involved in the transcriptional regulation of L-PAM-induced IFN-beta gene expression. Thus, the IFN-beta gene is an early response gene that is activated in response to L-PAM via a pathway that involves reactive oxygen species, and IFN-beta in turn plays an important role in L-PAM-induced TNF-alpha up-regulation.

Topics: Animals; Antineoplastic Agents, Alkylating; Cycloheximide; Dactinomycin; Female; Hydrogen Peroxide; Interferon-beta; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; RNA, Messenger; Tumor Necrosis Factor-alpha; Up-Regulation

The authors reported a case of a solitary mandibular plasmacytoma in a 53-year-old male Caucasian patient. The histological examination of the specimen was positive for a plasmacytoma with anaplastic appearance. Since the patient refused a demolitive surgical treatment, he was treated with a local radiation therapy of 4000 rads over a 20-day period and polychemotherapy with cyclophosphamide, prednisone and melphalan. Six years after starting radiation treatment the patient is free of recurrent primary disease and not affected by multiple localization. In conclusion, the solitary bone plasmacytoma represents an initial stage of the multiple myeloma rather than a distinct clinical pathology. Unfortunately, the diagnosis of the plasmacytoma is only rarely carried out in the early phases of the disease. The importance of the identification of the initial stage without a clear M component, as in the reported case, is self-evident, since the prognosis is related to the mass of plasmacytoma cells that are present at the time of the diagnosis. The purpose of this study is to report an extremely rare case of solitary bone plasmacytoma with a mandibular localization treated with radio- and polychemotherapy.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cyclophosphamide; Follow-Up Studies; Humans; Male; Mandibular Neoplasms; Melphalan; Middle Aged; Plasmacytoma; Prednisone; Prognosis; Radiotherapy Dosage; Remission Induction

We have previously shown that B7-2 (CD86) and, to a lesser extent, B7-1 (CD80) contribute to the curative effectiveness of low-dose melphalan (L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor under conditions that lead to the acquisition of potent cytotoxic T lymphocyte (CTL) activity at the tumor site. Since B7-1 and B7-2 are expressed on both tumor cells and host antigen-presenting cells (APC), the current studies were undertaken to examine the relative importance of each costimulatory molecule on tumor cells and on host APC for the acquisition of anti-MOPC-315 CTL activity. Utilizing an in vitro system for the acquisition of CTL activity, we found that B7 expression on host APC is important for the development of CTL activity in stimulation cultures of spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers, although the expression of either B7-1 or B7-2 is sufficient. In addition, we found that B7-2, which is expressed at high levels on stimulator tumor cells, but not B7-1, which is expressed at much lower levels, is also important for the acquisition of CTL activity. However, the vast majority of the CTL activity acquired in vitro in response to stimulation with the B7-2-expressing MOPC-315 tumor cells was found to depend on B7-expressing host APC. Thus, it is likely that B7-2, which is expressed at high levels on MOPC-315 tumor cells, promotes the rapid lysis of MOPC-315 stimulator tumor cells, thereby making tumor-associated antigens more readily available for efficient presentation by B7-expressing host APC which, in turn, stimulate the acquisition of CTL activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers.

Topics: Animals; Antigen Presentation; Antigens, CD; Antineoplastic Agents, Alkylating; B7-1 Antigen; B7-2 Antigen; Cytotoxicity, Immunologic; Female; Lymphocyte Cooperation; Melphalan; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmacytoma; Spleen; T-Lymphocytes, Cytotoxic

In this study, we show that administration of low-dose melphalan (l -PAM, l -phenylalanine mustard) to mice bearing a large MOPC-315 plasmacytoma led to a rapid up-regulation of B7-1 (CD80), but not B7-2 (CD86), expression on the surface of MOPC-315 tumor cells. This l -PAM-induced preferential up-regulation of B7-1 surface expression was due, at least in part, to a direct effect of l -PAM on the tumor cells, as in vitro exposure of MOPC-315 tumor cells to l -PAM led to the preferential up-regulation of B7-1 surface expression. Moreover, in vitro exposure of MOPC-315 tumor cells to two other anticancer modalities, gamma-irradiation and mitomycin C, resulted in the preferential up-regulation of B7-1 surface expression. This effect was not restricted to MOPC-315 tumor cells, as preferential up-regulation of B7-1 surface expression was observed also following in vitro exposure of the P815 mastocytoma (that is negative for both B7-1 and B7-2 surface expression) to any of the three anticancer modalities. The up-regulation of B7-1 surface expression following in vitro exposure of tumor cells to l -PAM, gamma-irradiation, or mitomycin C required de novo protein and RNA synthesis, and was associated with the accumulation of mRNA for B7-1 within 4-8 h, indicating that the regulation of B7-1 expression is at the RNA transcriptional level. These results have important implications for an additional immune-potentiating mechanism of these anticancer modalities in clinical setting.

Topics: Animals; Antibiotics, Antineoplastic; Antigens, CD; Antineoplastic Agents, Alkylating; B7-1 Antigen; B7-2 Antigen; Cell Membrane; Drug Administration Schedule; Gamma Rays; Gene Expression Regulation, Neoplastic; Injections, Intraperitoneal; Mast-Cell Sarcoma; Melphalan; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mitomycin; Neoplasm Transplantation; Plasmacytoma; Protein Biosynthesis; Proteins; RNA; Tumor Cells, Cultured; Up-Regulation

Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Cortisone; Drug Therapy, Combination; Female; Humans; Melphalan; Middle Aged; Nasopharyngeal Neoplasms; Plasmacytoma; Tomography, X-Ray Computed

Transplantation after high-dose chemotherapy prolongs survival in patients with multiple myeloma compared with standard therapy. It is unclear whether the optimal timing of transplantation is immediately after induction chemotherapy or whether stem cells may be cryopreserved for transplantation at subsequent progression or relapse. In this study, stem cells were collected within 6 months of diagnosis, followed by transplantation only at progression of myeloma. One hundred and eighteen patients with multiple myeloma had stem cells collected and cryopreserved. Eleven had transplants early in the disease after they demonstrated failure to respond to primary therapy. The remaining 107 were eligible for transplants when there was evidence of progressive disease. Of the 118 patients, 67 had transplants, nine died of progressive disease before transplantation, and 42 remain alive in plateau phase. The median survival of the group is 58.5 months; 67 are alive. Serum beta2-microglobulin, bone marrow labeling index (S phase), and hemoglobin level predicted overall survival (P < 0.006, P < 0.001, and P < 0.01, respectively). We conclude that early cryopreservation of blood stem cells followed by transplantation at progression is a feasible approach to therapy in patients with myeloma. The underlying biology of the disease has a greater impact on survival than the timing of transplantation. A prospective randomized trial is required to answer definitively the question of the optimal timing of blood cell transplantation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Bone Marrow; Carmustine; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Disease Progression; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Life Tables; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Neoplasm Proteins; Plasmacytoma; Prednisone; Salvage Therapy; Survival Analysis; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

We have previously shown that norepinephrine (NE) inhibits the in vitro generation of anti-MOPC-315 CTL activity by spleen cells from BALB/c mice rejecting a large MOPC-315 tumor as a consequence of low-dose melphalan (l -phenylalanine mustard (l -PAM)) treatment (l -PAM TuB spleen cells). Since TNF-alpha plays a key role in the generation of antitumor CTL activity in this system, we determined whether NE mediates this inhibition through inhibition of TNF-alpha production. Here, we show that NE inhibits the production of TNF-alpha protein and mRNA by l -PAM TuB spleen cells stimulated in vitro with mitomycin C-treated tumor cells. Flow cytometric analysis of intracellular expression of TNF-alpha revealed substantial NE-mediated decreases in the percentages of TNF-alpha+ cells among CD4+ and CD8+ T cells and F4/80+ activated macrophages. NE inhibition of CTL generation was largely overcome by addition of TNF-alpha to the stimulation cultures. When the beta-adrenergic antagonist propranolol was added to the stimulation cultures of l -PAM TuB spleen cells at a concentration that prevented NE-induced cAMP elevation, the NE-mediated decrease in TNF-alpha mRNA and NE-mediated inhibition of CTL generation were reversed. Collectively, these results suggest that NE inhibits antitumor CTL generation, at least in part, by inhibiting TNF-alpha synthesis through a mechanism(s) involving beta-adrenergic receptor signaling.

Topics: Animals; Antigens, Differentiation; CD3 Complex; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Female; Gene Expression Regulation, Neoplastic; Intracellular Fluid; Lymphocyte Activation; Lymphocyte Subsets; Macrophages; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Norepinephrine; Plasmacytoma; Propranolol; Receptors, Adrenergic, beta; RNA, Messenger; Spleen; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

We have previously shown that low dose melphalan (L-phenylalanine mustard; L-PAM) therapy of hitherto immunosuppressed mice bearing a large (20-mm) s.c. MOPC-315 tumor leads to the acquisition of potent CD8+ T cell-mediated antitumor immunity which in turn eradicates the large tumor burden not eradicated by the direct antitumor effects of the drug. Here we show the preferential importance of the B7-2 costimulatory molecule for the curative effectiveness of low dose L-PAM for mice bearing a large MOPC-315 tumor by demonstrating that treatment with anti-B7-2 mAb, but not anti-B7-1 mAb, reduced the percentage of mice cured by the low dose L-PAM. In addition, we show the preferential importance of the B7-2 molecule for the low dose L-PAM-induced acquisition of the ability of tumor-infiltrating lymphocytes from MOPC-315 tumor bearers to secrete IL-2 and IFN-gamma as well as to exert an anti-MOPC-315 CTL effect. The preferential importance of the B7-2 molecule may be due to the higher level of B7-2 than of B7-1 expression on B220+ cells and on tumor cells from the s.c. tumor nodule of low dose L-PAM-treated MOPC-315 tumor bearers and the selective up-regulation of the B7-2 molecule in the draining of these mice. Thus, the B7-2 molecule plays a dominant role in the acquisition of T cell-dependent tumor-eradicating immunity in low dose L-PAM-treated mice bearing a large MOPC-315 tumor, suggesting that one of the mechanisms by which chemotherapy may enhance antitumor immunity is through up-regulation of critical costimulatory molecules that enhance antitumor responses.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; B7-1 Antigen; B7-2 Antigen; Drug Administration Schedule; Female; Injections, Intraperitoneal; Interferon-gamma; Interleukin-2; Lymph Nodes; Lymphocytes, Tumor-Infiltrating; Melphalan; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Plasmacytoma; T-Lymphocytes, Cytotoxic

Our previous results have indicated that mice whose plasmacytoma regressed following curative melphalan chemotherapy manifested various persistent immunohematological abnormalities including immunosuppression, myeloproliferation, as well as excessive production of and response to growth factors. Mice not bearing plasmacytoma treated with an identical dose of melphalan chemotherapy did not exhibit such abnormalities. In the present study we show that plasmacytoma-regressor mice (PRM) contain preleukemic cells which do not progress to leukemia in these mice. However, adoptive transfer of splenocytes originating in PRM to preirradiated but otherwise untreated syngeneic recipients resulted in the development of overt leukemia in these recipients. The presence of leukemia in the primary recipient mice was ascertained by blood counts as well as by spleen histology. Furthermore, splenocytes from the irradiated primary recipients adoptively transferred to non-irradiated secondary recipients caused leukemia formation in 100% of the secondary recipients. Sex chromosome analysis of the leukemic cells in the irradiated primary recipients clearly showed that they originated in the PRM donors. Two leukemic lines were established from leukemias developing in the secondary recipients and both expressed surface markers of hematopoietic progenitor cells as well as markers of T cells. We suggest that PRM could serve as an animal model to investigate development of chemotherapy-related leukemia in humans.

Topics: Animals; Antineoplastic Agents, Alkylating; Female; Karyotyping; Leukocyte Count; Male; Melphalan; Mice; Mice, Inbred BALB C; Phenotype; Plasmacytoma; Preleukemia; Spleen; Time Factors

We report eight patients with a solitary plasmacytoma of the spine associated with neurological complications. The patients included five men and three women with an average age at presentation of 59 years (range, 47 to 73 years). The tumour was confined to the thoracic spine in six cases, cervical spine in one and lumbar spine in one. Duration of symptoms ranged from 2.5 to 22 months. Treatment consisted of a combination of radiotherapy, melphalan and surgery. One patient progressed to multiple myeloma 7 years after surgery. Surgical treatment (anterior surgery in three cases and posterior surgery in five) produced neurological improvement in all patients. We stress the importance of an early diagnosis followed by appropriate treatment including surgery for this clinical entity and long-term follow-up to detect a disseminated disease.

Topics: Aged; Antineoplastic Agents, Alkylating; Cervical Vertebrae; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Laminectomy; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Multiple Myeloma; Neurologic Examination; Peripheral Nervous System Diseases; Plasmacytoma; Radiography; Radiotherapy; Spinal Neoplasms; Survival Rate; Thoracic Vertebrae; Treatment Outcome

CTLA-4 blockade has been shown by other investigators [D. R. Leach, et al., Science (Washington DC), 271: 1734-1736, 1996; and Y-F. Yang, et al., Cancer Res., 57: 4036-4041, 1997] to retard tumor growth in selected tumor systems. Here, we show that CTLA-4 blockade alone was ineffective in retarding tumor growth in the murine MOPC-315 tumor system. Yet, CTLA-4 blockade offered significant therapeutic benefits to MOPC-315 tumor bearers when combined with a subtherapeutic dose of the chemotherapeutic agent melphalan, which was previously shown (L. Gorelik, et al., Cancer Immunol. Immunother., 39: 117-126, 1994) to shift the cytokine profile in the tumor bearers toward type-1 cytokines. In addition, we show here that anti-CTLA-4 monoclonal antibody enhanced antitumor cytotoxicity when the anti-CTLA-4 monoclonal antibody was added to stimulation cultures of spleen cells from low-dose melphalan-treated MOPC-315 tumor-bearing mice but not from untreated tumor-bearing mice. These results suggest that the therapeutic benefits of CTLA-4 blockade depend on the ability of drugs such as melphalan to promote an immunogenic environment by altering the cytokine profile of tumor-specific T cells.

Topics: Abatacept; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Antineoplastic Agents, Alkylating; Combined Modality Therapy; CTLA-4 Antigen; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Female; Immunoconjugates; Immunotherapy; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmacytoma; Spleen; T-Lymphocytes; Tumor Cells, Cultured

A case of primary nonsecretory plasmacytoma of the spleen is reported. On laparotomy and splenectomy a 920 g spleen was removed, measuring 16 x 14 x 6 cm. The cut surface of the entire spleen showed that the tumour occupied most of the splenic tissue. A bone marrow aspirate and trephine, skeletal survey showed no signs of myeloma. Biopsy of the liver and regional lymph nodes was normal. Immunocytochemistry of the splenic tumour showed positivity for pan-B and plasma cell markers. After splenectomy the patient was treated with chemotherapy according to protocol VBCMP (M2).

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisone; Splenectomy; Splenic Neoplasms; Vincristine

An elderly patient with extramedullary lung plasmacytoma and subsequent pleural effusion is described. The presence of abnormal plasma cells in the pleural fluid led to diagnosis. Histologically similar conditions such as multiple myeloma and solitary myeloma of bone were ruled out by clinical evaluation. These neoplasms usually occur in the head and neck area and are not characterized by paraprotein accumulation. Few cases in the lung have been reported. We describe a case of extramedullary plasmacytoma of the lung with plasmacytoma-induced pleural effusion and the presence of monoclonal paraprotein in both the serum and urine. Chemotherapy with melphalan was effective in reducing the size of the plasmacytoma, and pleurodesis was used to manage the pleural effusion.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Humans; Lung Neoplasms; Male; Melphalan; Plasmacytoma; Pleural Effusion, Malignant; Pleurodesis

Simultaneous occurrence of localized plasmacytomas of both hands and feet has not been reported so far. Here we report a 40-year old female patient, who had at presentation pain and deformity. Of hands and feet, with numerous cystic lytic lesions of phalangeal, metacarpal and metatarsal bones, detected by X-rays. The biopsy of the affected bone showed moderately differentiated plasmacytoma of lambda light chain type (lambda-LC). Serum and urine biochemical analysis revealed the existence of lambda LC monoclonal component. The patient was treated by local radiotherapy and subsequent systemic chemotherapy, which consisted of 3 cycles of the M-2 protocol and 7 cycles of melphalan-prednisone. Five years after the diagnosis, the absence of plasmacytoma was confirmed by puncture biopsy of the left hand phalanx. Monoclonal protein in serum and urine was not detected.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carmustine; Combined Modality Therapy; Cyclophosphamide; Female; Fingers; Foot Diseases; Hand Deformities, Acquired; Humans; Melphalan; Metacarpus; Plasmacytoma; Prednisone; Vincristine

We present two cases of extramedullary plasmacytoma presenting as a mediastinal mass and preceding the onset of full-blown multiple myeloma. The patients are a 62-year-old woman who presented with progressive dyspnea and left-sided chest pain and a 59-year-old asymptomatic man. In both patients, radiographic studies revealed a posterior and anterior mediastinal mass, respectively. Surgical resection of the tumor was performed in the two cases. The tumors were characterized by a well-circumscribed proliferation of plasma cells surrounded by residual lymph nodal tissue. Immunohistochemical studies on paraffin sections demonstrated lambda light chain restriction. Follow-up in our patients revealed that both of them developed multiple myeloma after 6 months and 2 years, respectively. One patient received treatment with melphalan and prednisone and is currently alive and well without evidence of disease, 2 years after diagnosis. The second patient died 4 years after resection of his tumor with evidence of disease in lumbar spine, skull, and lungs. Extramedullary plasmacytoma presenting as a mediastinal mass may precede the onset of full-blown multiple myeloma; therefore, institution of early systemic therapy in these patients may be of value in preventing further progression of the disease.

Topics: Chest Pain; Combined Modality Therapy; Diagnosis, Differential; Dyspnea; Fatal Outcome; Female; Humans; Immunoglobulin lambda-Chains; Male; Mediastinal Neoplasms; Melphalan; Middle Aged; Multiple Myeloma; Plasma Cells; Plasmacytoma; Prednisone

Topics: Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Humans; Immunoglobulin kappa-Chains; Intestinal Diseases; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisolone; Remission Induction; Stomach Diseases

We have previously shown the importance of the acquisition of CD8+ T cell-dependent tumor-eradicating immunity for the curative effectiveness of low dose melphalan (L-PAM, L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor. Here we show the importance of TNF production for the curative effectiveness of low dose L-PAM for such tumor-bearing mice. Studies regarding the mechanism(s) through which TNF exerts its antitumor effects in L-PAM-treated MOPC-315 tumor-bearing mice (L-PAM TuB mice) revealed that MOPC-315 tumor cells are not sensitive to the cytotoxic effects of TNF either before or after the chemotherapy. However, TNF is essential for the in vitro generation of potent CTL activity by CD8+ T cells from L-PAM TuB mice. Moreover, addition of exogenous TNF to in vitro stimulation cultures of spleen cells from untreated mice bearing a large MOPC-315 tumor resulted in the generation of a greatly enhanced CTL activity against MOPC-315-associated Ags. Finally, we have previously shown that TCR V beta 8+/CD8+ T cells are involved in the curative effectiveness of low dose L-PAM for mice bearing a large MOPC-315 tumor. Here we show that TNF is important for the ability of MOPC-315-specific V beta 8+/CD8+ T cell lines from L-PAM TuB mice to bring about tumor eradication upon adoptive transfer into tumor-bearing mice. Taken together, these studies illustrate that low dose L-PAM mediates its therapeutic effectiveness for mice bearing a large MOPC-315 tumor, at least in part, via TNF production (e.g., by V beta 8+/CD8+ T cells), which in turn promotes the generation of anti-MOPC-315 CTL activity.

Topics: Animals; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Female; Immunity, Cellular; Immunization, Passive; Melphalan; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Plasmacytoma; Spleen; Survival Analysis; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha

Topics: Acute Kidney Injury; Aged; Humans; Kidney Tubules; Male; Melphalan; Plasmacytoma; Plasmapheresis; Prednisolone; Splenectomy; Splenic Neoplasms

We have previously shown the importance of endogenous tumor necrosis factor (TNF) production for the curative effectiveness of low-dose melphalan (L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor. In the current study we demonstrate that low-dose melphalan is actually associated with enhanced expression of mRNA for TNF alpha in the s.c. tumor nodule. Moreover, the expression of mRNA for interferon gamma (IFN gamma) and interleukin-12 (IL-12; p40) is also elevated at the tumor site. However, while elevation in the expression of mRNA for TNF alpha and IFN gamma is evident within 24 h after the chemotherapy, elevation in the expression of mRNA for IL-12(p40) is first evident 72 h after the chemotherapy. Moreover, neutralizing anti-IFN gamma mAb, like neutralizing anti-TNF mAb but not neutralizing anti-IL-12 mAb, reduced the curative effectiveness of low-dose melphalan for MOPC-315 tumor bearers. Studies into the mechanism through which IFN gamma mediates its antitumor effect in low-dose-melphalan-treated MOPC-315 tumor-bearing mice revealed that MOPC-315 tumor cells, which are not sensitive to the direct antitumor effects of TNF, display some sensitivity to the antiproliferative activity of high concentrations of IFN gamma. However, unlike TNF alpha, IFN gamma is unable to promote the generation of anti-MOPC-315 cytotoxic T lymphocyte activity and, in fact, exerts an inhibitory activity on CTL generation. Taken together, our studies illustrate that low-dose melphalan therapy of MOPC-315 tumor bearers is associated with the rapid elevation in the expression of mRNA for IFN gamma and TNF, two cytokines which are important for the curative effectiveness of low-dose melphalan, and which mediate their antitumor effect, in part, through distinct mechanisms.

Topics: Animals; Antineoplastic Agents, Alkylating; Base Sequence; Cytotoxicity, Immunologic; Female; Gene Expression Regulation, Neoplastic; Injections, Subcutaneous; Interferon-gamma; Melphalan; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neoplasm Transplantation; Plasmacytoma; Polymerase Chain Reaction; RNA, Messenger; Stimulation, Chemical; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

A 56-year-old apparently healthy man was on routine examination found to have a paraproteinaemia, classified as an IgG-lambda plasmocytoma in stage 1 on the basis of a raised IgG level (1950 mg/dl) and partly binuclear plasma cells in bone marrow. When 5 months later the IgG concentration had increased to 2980 mg/dl and the proportion of plasma cells in bone marrow to 15%, treatment was begun with melphalan (0.25 mg/kg) and prednisolone (2 mg/kg), both on 4 successive days every 6 weeks. The patient's general condition rapidly worsened after 6 months. The extent of osteolysis increased, necessitating radiotherapy of the vertebrae as well as a change in treatment to vincristine, cyclophosphamide, doxorubicin and prednisolone. At that time renal failure set in. But the prophylactically placed Cimino shunt had become infiltrated with plasma cells causing shunt stenosis and soft-tissue swelling. The infiltration was reduced by irradiation with 18 Gy. Numerous bluish skin discolorations now appeared and plasma cell infiltrates were shown in lung and pleura, as well as in the abdomen. The patient died 15 months after the diagnosis had been made.

Topics: Antineoplastic Combined Chemotherapy Protocols; Arteriovenous Shunt, Surgical; Bone Marrow; Constriction, Pathologic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Immunoglobulin G; Immunoglobulin lambda-Chains; Male; Melphalan; Middle Aged; Plasma Cells; Plasmacytoma; Prednisolone; Vincristine

The current studies demonstrate that MOPC-315 tumor cells secrete large amounts of interleukin-10 (IL-10), which contributes to the inhibitory activity of MOPC-315 culture supernatants for the in vitro generation of antitumor cytotoxicity by MOPC-315-"immune" spleen cells. Moreover, addition of neutralizing monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of cells from the tumor infiltrated spleens of mice bearing a large MOPC-315 tumor resulted in the generation of enhanced anti-MOPC-315 cytotoxicity. In contrast, addition of monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of splenic cells from mice that are in the final stages of immune-mediated tumor eradication as a consequence of low-dose melphalan (L-phenylalanine mustard; L-PAM) therapy (and whose spleens no longer contain metastatic tumor cells) did not lead to enhancement in the in vitro generation of antitumor cytotoxicity. The cessation of IL-10 secretion as a consequence of low-dose L-PAM therapy of MOPC-315 tumor bearers was found to be accompanied by the acquisition of the ability to secrete interferon gamma (IFN gamma) by the splenic cells. In addition, by day 2 after low-dose L-PAM therapy a drastic decrease in the amount of IL-10 secreted by the s.c. tumor nodules was noted, which preceded the accumulation of tumor-infiltrating lymphocytes capable of secreting IFN gamma. Thus, low-dose L-PAM therapy of mice bearing a large MOPC-315 tumor leads to a shift in cytokine production from a Th2-type cytokine to a Th1-type cytokine, and it is conceivable that this shift in cytokine production plays an important role in the low-dose L-PAM-induced acquisition of antitumor immunity by hitherto immunosuppressed mice bearing a large MOPC-315 tumor.

Topics: Animals; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Female; Immunocompromised Host; Interferon-gamma; Interleukin-10; Lymphocytes, Tumor-Infiltrating; Melphalan; Mice; Mice, Inbred BALB C; Mitomycin; Neoplasm Transplantation; Plasmacytoma; Spleen; Stimulation, Chemical; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured

We have previously shown that depletion of TCR-V beta 8+ T cells by treatment with mAb reduces the curative effectiveness of low dose melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large MOPC-315 tumor and extensive metastases. Here we show that V beta 8+/CD8+ T cell lines derived from mice that are in the process of immune-mediated eradication of a large MOPC-315 tumor as a consequence of low dose L-PAM therapy (L-PAM TuB mice) are capable of mediating tumor eradication in vivo upon adoptive transfer. Analysis of the possible mechanisms through which these cell lines bring about tumor eradication revealed that the V beta 8+/CD8+ cells can exert in vitro a potent lytic activity and secrete large amounts of IFN-gamma. Both of these activities can be triggered by the MOPC-315 but not the MOPC-104E plasmacytoma and are restricted by the MHC class I H-2Kd molecule. In vivo neutralization of IFN-gamma by treatment with mAb was found to cause a noticeable delay in tumor rejection in mice subjected to adoptive chemoimmunotherapy with low dose L-PAM and V beta 8+/CD8+ cells; however, all tumors did regress after initial growth. Thus, the V beta 8+/CD8+ cells use an IFN-gamma-dependent mechanism for the realization of their in vivo tumor-eradicating immunity. However, an IFN-gamma-independent mechanism, most likely involving direct V beta 8+/CD8+ CTL activity, is apparently also used.

Topics: Animals; CD8 Antigens; Cytokines; Cytotoxicity, Immunologic; Immunity, Cellular; Immunotherapy, Adoptive; Melphalan; Mice; Neoplasms, Experimental; Plasmacytoma; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic

We have recently demonstrated the importance of V beta 8+/CD8+ cells for the curative effectiveness of a suboptimal low dose (0.75 mg/kg) of melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large s.c. MOPC-315 tumor and extensive metastases. Here we show that staphylococcal enterotoxin B (SEB), which is known to selectively stimulate T cells expressing members of the TCR-V beta 8 gene family, substantially improved the curative effectiveness of the suboptimal dose of L-PAM for mice bearing a large MOPC-315 tumor. Moreover, treatment of mice with mAb F23.1 (anti-V beta 8) abrogated the in vivo therapeutic effect of SEB for low dose L-PAM-treated MOPC-315 tumor bearers (L-PAM TuB mice). Analysis of the effect of SEB on the tumor-infiltrating lymphocytes (TILs) demonstrated that the SEB-mediated therapeutic effect was associated with a significant increase in: 1) the percentage of V beta 8+ cells among the CD8+ T cells that accumulated in the s.c. tumor nodules, 2) the total number of V beta 8+/CD8+ cells present per tumor on day 4 after low dose L-PAM therapy, and 3) the ability of the TILs to lyse MOPC-315 tumor cells in vitro in a short term assay. Furthermore, treatment of mice with mAb F23.1 abolished the ability of SEB to render the TIL population of L-PAM TuB mice more cytotoxic in vitro for MOPC-315 tumor cells. Thus, the SEB-mediated improvement in the therapeutic outcome of low dose L-PAM therapy for mice bearing a large MOPC-315 tumor may be due in part to SEB-mediated increase in the contribution of the V beta 8+ T cells to tumor eradication through enhancement in the magnitude of the anti-MOPC-315 lytic activity exhibited by the TIL population.

Topics: Animals; CD8 Antigens; Cytotoxicity, Immunologic; Enterotoxins; Female; Immunity, Cellular; Lymphocytes, Tumor-Infiltrating; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Plasmacytoma; Survival Analysis

We have previously shown that treatment of mice bearing a large MOPC-315 plasmacytoma with a low dose of the anticancer drug melphalan (L-phenylalanine mustard; L-PAM) results in the acquisition of a potent CD8+ T-cell-mediated anti-MOPC-315 cytotoxic T lymphocyte (CTL) activity by the hitherto immunosuppressed tumor bearers, and this immunity contributes to complete tumor eradication. In the studies presented here, we sought to determine how the acquisition of this antitumor immunity following low-dose chemotherapy is possible, in light of the report that MOPC-315 tumor cells produce transforming growth factor-beta (TGF-beta), an immunosuppressive cytokine that can down-regulate the generation of CTL responses. We found that the acquisition of CTL activity following low-dose L-PAM therapy is not due to a chemotherapy-induced decrease in the sensitivity of MOPC-315 tumor bearer spleen cells to TGF-beta-mediated inhibition of CTL generation. Moreover, even spleen cells from MOPC-315 tumor-bearing mice, which had received L-PAM therapy 7 days earlier and had acquired CTL activity in vivo, were sensitive to the inhibitory activity of TGF-beta upon culture for as little as 1 day, with or without stimulator tumor cells. However, the production of TGF-beta by MOPC-315 tumors decreased drastically as a consequence of the low-dose chemotherapy. Thus, the curative effectiveness of low-dose L-PAM therapy for MOPC-315 tumor-bearing mice may be due, at least in part, to a reduction in TGF-beta production that enables the development of tumor-eradicating immunity.

Topics: Animals; Cells, Cultured; Cytotoxicity, Immunologic; Down-Regulation; Female; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Spleen; T-Lymphocytes, Cytotoxic; Transforming Growth Factor beta

MOPC-315 plasmacytoma-bearing BALB/c mice were treated with high doses of melphalan, causing a permanent and complete regression of the tumor. In the present study we analyzed plasmacytoma-regressor mice (PRM) 3-6 months after plasmacytoma regression. A second group of otherwise untreated normal mice was treated with melphalan (M--control group). A third group of mice remained untreated and served as an age- and sex-matched control group. PRM were cachectic and had an increased mortality rate compared to the M and the C control groups. Histopathological examination indicated that the spleen of PRM showed pronounced abnormalities, primarily in the red pulp. These abnormalities consisted of extramedullary hematopoiesis and myeloid-granulocytic hyperplasia. Spleens of M mice showed similar abnormalities but to a much lesser extent. Flow cytometric analysis of cellular surface markers of PRM splenocytes indicated a high number of large MAC-I- and GR-I-positive cells compared to splenocytes of M or C controls. These large cells also expressed Fc tau receptors (Fc tau RII), stained positively with non-specific esterase and adhered to plastic dishes; a certain percentage expressed MAC-2 and MAC-3 antigens. A quantitative suppression of CD4+ T cells and of B cells was also shown. Circulating levels of TNF were higher in PRM than in M or C mice. The capacity of splenocytes from PRM to secrete factors that stimulated CFU-GM colony formation in soft agar by bone-marrow cells from normal mice was significantly up-regulated compared to that of splenocytes from M or C mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bone Marrow Cells; Cachexia; Cell Division; Colony-Stimulating Factors; Cytokines; Granulocytes; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Phenotype; Plasmacytoma; Spleen; Splenomegaly; Time Factors

Stage-3 extramedullary plasmacytoma of the large intestine was diagnosed in an 8-year-old Labrador Retriever. Three primary tumors were located in the colon and rectum, with metastasis to local lymph nodes and the spleen. The disease was associated with a monoclonal serum protein spike identified as IgG. Treatment consisted of surgical excision followed by chemotherapy, using melphalan and prednisone. The dog remained free from clinical signs of disease and adverse effects of the chemotherapy at 9 months. Findings in this dog indicated that extramedullary plasmacytoma may be an aggressive disease, associated with spread to distant sites and monoclonal gammopathy.

Topics: Animals; Biopsy, Needle; Blood Protein Electrophoresis; Chemotherapy, Adjuvant; Colonic Neoplasms; Dog Diseases; Dogs; gamma-Globulins; Lymphatic Metastasis; Male; Melphalan; Plasmacytoma; Prednisone; Rectal Neoplasms; Splenic Neoplasms

We have previously shown that the curative efficacy of low dose melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large s.c. MOPC-315 tumor requires the participation of CD8+ (but not CD4+) T cell-dependent antitumor immunity. Here we show that CD8+ T cells obtained from regressing tumors on day 4 or 5 after low dose L-PAM therapy of MOPC-315 tumor bearers (L-PAM TuB mice) display a preferential enhancement in the utilization of the TCR-V beta 8.3 gene segment as compared to CD8+ T cells from normal lymph nodes. Treatment of L-PAM TuB mice with mAb F23.1, which leads to the depletion of V beta 8.3+ cells, as well as V beta 8.1 and 8.2+ cells, led to a significant reduction in the ability of their tumor-infiltrating lymphocytes as well as their spleen cells to lyse MOPC-315 tumor cells in vitro in a short term assay. In addition, the mAb F23.1 treatment almost completely abrogated the lytic activity of the tumor-infiltrating lymphocytes against another syngeneic, antigenically related plasmacytoma (the MOPC-104E). Moreover, the mAb F23.1 treatment significantly reduced the curative effectiveness of low dose L-PAM for mice bearing a large MOPC-315 tumor. In contrast, mAb KJ16 treatment, which leads to the depletion of V beta 8.1 and 8.2+ cells (but not V beta 8.3+ cells), did not reduce significantly the curative effectiveness of low dose L-PAM for such MOPC-315 tumor bearers. Thus, V beta 8.3+ T cells are important for the curative effectiveness of low dose L-PAM therapy for MOPC-315 tumor bearers, and it is conceivable that the V beta 8.3+ cells mediate their effect (at least in part) by contributing to the acquisition of CTL activity against plasmacytoma-shared Ag.

Topics: Animals; Antibodies, Monoclonal; CD8 Antigens; Cytotoxicity, Immunologic; Female; Lymphocytes, Tumor-Infiltrating; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocyte Subsets

We have shown previously that thymocytes from MOPC-315-tumor-bearing mice treated with low-dose melphalan (L-phenylalanine mustard) (L-PAM TuB mice) are superior to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated normal mice or normal mice treated with low-dose melphalan in their ability to generate an antitumor cytotoxic response following 5-day in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL-2) [Mokyr MB, Bartik MM, Ahn M-C (1989) Cancer Res 49; 870]. Here we characterize the rIL-2 requirements for the generation of enhanced antitumor cytotoxicity by L-PAM TuB thymocytes relative to normal thymocytes upon in vitro stimulation with MOPC-315 tumor cells. Specifically, we show that delaying the addition of a low concentration of rIL-2 to 5-day in vitro stimulation cultures of thymocytes resulted in a progressive decline in the generation of antitumor cytotoxicity by both normal and L-PAM TuB thymocytes. However, even when rIL-2 was added on day 2 after culture initiation, thymocytes from L-PAM TuB mice generated a more potent antitumor cytotoxicity than did thymocytes from normal mice. In addition, when rIL-2 was added at the time of culture initiation, replacement of the conditioned medium with fresh medium lacking rIL-2 on day 3 of the 5-day in vitro stimulation culture period eliminated the ability of normal thymocytes, and reduced (but did not eliminate) the ability of L-PAM TuB thymocytes, to generate a significant level of antitumor cytotoxicity. A low concentration of fresh rIL-2 was sufficient to restore completely the generation of antitumor cytotoxicity by normal or L-PAM TuB thymocytes when added to the stimulation cultures immediately after the removal of the rIL-2-containing conditioned medium. The same low concentration of rIL-2 was also sufficient for restoring the generation of antitumor cytotoxicity by cultures of L-PAM TuB thymocytes, but not normal thymocytes, from which the rIL-2-containing medium was removed 1 day earlier. At the same time, conditioned medium from stimulation cultures of L-PAM TuB thymocytes was not superior to conditioned medium from stimulation cultures of normal thymocytes in supporting the generation of antitumor cytotoxicity by either normal or L-PAM TuB thymocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Drug Screening Assays, Antitumor; Female; Interleukin-2; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Recombinant Proteins; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured

We report a case of extramedullary plasmacytoma that appeared in an uncharacteristic manner as an ulcerative stomatitis affecting particularly the tongue and buccal mucosa. The lesions were associated with a transient lichenoid skin rash. The literature is reviewed and comparisons made between this tumor and the related plasma cell dyscrasias of multiple myeloma and monoclonal gammopathy.

Topics: Aged; Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin kappa-Chains; Lichenoid Eruptions; Melphalan; Mouth Neoplasms; Plasmacytoma; Stomatitis; Ulcer

Spleen cells from BALB/c mice that are in the process of eradicating a large MOPC-315 tumor following low-dose L-PAM therapy (L-PAM TuB spleen cells) were previously shown to be capable of bringing about the complete regression of a large (15 to 20 mm) s.c. MOPC-315 tumor in a substantial percentage of T-cell-deficient (athymic nude) mice that had been treated with low-dose L-PAM (adoptive chemo-immunotherapy; ACIT). Here we show that aggressive depletion of CD4+T-cells by treatment both of spleen-cell donors and of recipients with anti-L3T4 monoclonal antibody (MAb) greatly improved the therapeutic effectiveness of L-PAM TuB spleen cells in ACIT. In the light of the apparent importance of cytotoxic T-lymphocytes (CTLs) for tumor eradication in low-dose L-PAM-treated MOPC-315-tumor bearers, it is interesting that treatment of L-PAM TuB spleen-cell donors with anti-L3T4 MAb was found to result in the generation of enhanced splenic anti-MOPC-315 cytotoxicity. Although most athymic nude mice in which the tumor had apparently completely regressed following ACIT remained tumor-free, approximately 1/3 of the mice relapsed. However, a substantial percentage of the relapsing mice were rescued by a low dose of L-PAM, which was not effective in causing tumor regression in athymic nude mice bearing a comparably large tumor if the mice had not been subjected previously to ACIT. Almost all athymic nude mice that had been "cured" of a large MOPC-315 tumor by ACIT but did not resist a subsequent MOPC-315 tumor challenge were rescued by low dose L-PAM. Thus, the therapeutic effectiveness of L-PAM TuB spleen cells in ACIT may be improved by aggressive depletion of CD4+ T-cells, suggesting that a low dose of L-PAM, which leads to the acquisition of potent splenic-tumor-eradicating immunity in BALB/c mice bearing a large MOPC-315 tumor, does not eliminate completely (or possibly not at all) the inhibitory activity of CD4+ T-cells. In addition, athymic nude mice that are not endowed with fully protective tumor-eradicating immunity following ACIT still have a substantial residual anti-tumor immune potential that can be exploited to bring about eradication of a large tumor burden following low-dose L-PAM therapy.

Topics: Animals; Drug Screening Assays, Antitumor; Female; Immunotherapy, Adoptive; Melphalan; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Recurrence, Local; Neoplasm Transplantation; Plasmacytoma; Spleen; T-Lymphocytes; Time Factors

We have previously shown that thymocytes from low-dose melphalan (L-phenylalanine mustard)-treated MOPC-315-tumor-bearing mice (melphalan TuB) are able to generate an enhanced level of anti-MOPC-315 cytotoxicity, as compared to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated or low-dose melphalan-treated normal mice, upon in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL-2). Here we show that the generation of enhanced anti-MOPC-315 cytotoxicity by melphalan TuB thymocytes depends on the ability of the thymocytes to proliferate. In addition, the ability of melphalan TuB thymocytes to generate an enhanced level of anti-MOPC-315 cytotoxicity correlated with their ability to proliferate more readily than thymocytes from untreated tumor-bearing mice and thymocytes from untreated or melphalan-treated normal mice in response to stimulation with MOPC-315 tumor cells plus a low concentration of rIL-2. Moreover, although fresh melphalan TuB thymocytes do not contain a higher percentage of phenotypically mature cells (i.e., CD4-/CD8+ or CD4+/CD8-) than do thymocytes from normal mice or untreated tumor-bearing mice, after a 5-day culture with both MOPC-315 tumor cells and a low concentration of rIL-2, cultures of thymocytes from melphalan TuB contained a much higher percentage of CD4-/CD8+ (but not CD4+/CD8-) cells than did cultures of thymocytes from the other two sources. Since CD4-/CD8+ cells were previously shown to be responsible for the exertion of antitumor cytotoxicity by thymocytes stimulated with MOPC-315 in vitro, our results indicate that the enhanced antitumor cytotoxicity exerted by melphalan TuB thymocytes following in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of rIL-2 is due, at least in part, to an expansion of the pool of CD4-/CD8+ effector cells.

Topics: Animals; CD4-CD8 Ratio; CD8 Antigens; Cytotoxicity, Immunologic; Female; Interleukin-2; Lymphocyte Activation; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Recombinant Proteins; T-Lymphocyte Subsets; Thymoma

Two murine tumour models, the L1210 leukaemia and the ADJ/PC6 plasmacytoma, have featured prominently in the preclinical development of platinum drugs. Mindful of the unequivocal need to discover new platinum-based drugs exhibiting activity in cisplatin/carboplatin refractory and relapsed cancers, and to devise clinically-predictive screening models, we have generated resistance in vivo in the ADJ/PC6 plasmacytoma to cisplatin (19- to 21-fold), to carboplatin (25-fold), iproplatin (greater than 14-fold) and tetraplatin (10-fold). The chemo-sensitivity profiles of these tumours have been compared with L1210 leukaemia lines resistant to either cisplatin (10-fold) or tetraplatin (34-fold). In cross-resistance studies, the L1210 and ADJ/PC6 resistant variants provided conflicting predictions of structures likely to circumvent cisplatin-acquired resistance. In particular, the L1210/cisplatin resistant model exhibited cross-resistance to carboplatin and iproplatin, whereas the diaminocyclohexane (DACH)-containing complex, tetraplatin, was even more active in the cisplatin resistant tumour than in the 'wild-type' tumour. The ADJ/PC6/cisplatin resistant tumour, however, was cross-resistant, not only to carboplatin and iproplatin, but also to tetraplatin. These data provide an important caveat on the adoption of single acquired resistant animal tumour models for platinum drug development.

Topics: Animals; Carboplatin; Cell Line, Transformed; Cisplatin; Drug Resistance; Drug Screening Assays, Antitumor; Female; Leukemia; Melphalan; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Organoplatinum Compounds; Plasmacytoma

The work is based on the related literature and describes clinical features of plasmocytoma solitary of soft tissues and maxillofacial bones. A case of extramedullary maxillary sinus plasmocytoma a 39-year-old man is described. Attention has been called to diagnostic difficulties in this type of tumour.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Humans; Lomustine; Male; Maxillary Sinus Neoplasms; Melphalan; Plasmacytoma; Prednisone

We have previously shown that while spleen cells from untreated mice bearing a large MOPC-315 tumor are not cytotoxic in vitro for MOPC-315 tumor cells, spleen cells obtained from such mice on day 7 after low-dose melphalan (L-phenylalanine mustard); L-PAM therapy exert a substantial anti-MOPC-315 cytotoxicity [Mokyr et al. (1989) Cancer Res 49: 4597]. Here we show that this anti-MOPC-315 lytic activity is evident by day 5, and peaks on day 7 after the low-dose chemotherapy, at a time when the mice are actively engaged in tumor eradication. Short-term exposure of spleen cells from mice bearing a MOPC-315 tumor and treated with low-dose L-PAM (L-PAM TuB mice) to phorbol 12-myristate 13-acetate (PMA) was found to enhance greatly the ability of these spleen cells to lyse MOPC-315 tumor cells. The highest level of anti-MOPC-315 cytotoxicity was obtained when spleen cells from tumor-bearing mice that had received chemotherapy 7 days earlier were exposed to PMA at a concentration of 1-10 ng/ml. The exertion of the enhanced anti-MOPC-315 lytic activity by L-PAM TuB spleen cells exposed to PMA was found to require CD8+, but not CD4+, T cells. The apparent specificity of the lytic activity exerted by the PMA-stimulated L-PAM TuB spleen cells was illustrated not only by the inability of the spleen cells to lyse an allogeneic, antigenically unrelated thymoma (EL4), but also by their relatively weak lytic activity for two antigenically related syngeneic plasmacytomas. In addition, when EL4 target cells were admixed with MOPC-315 tumor cells, the lytic activity triggered in the L-PAM TuB spleen cells by the MOPC-315 tumor cells plus PMA was not effective in lysing the antigenically unrelated target cells. Moreover, even in the presence of the calcium-specific ionophore, ionomycin, L-PAM TuB spleen cells exposed to PMA were unable to lyse the EL4 target cells. Thus, fresh CD8+ splenic T cells from L-PAM TuB mice that are in the process of eradicating a large MOPC-315 tumor as a consequence of low-dose L-PAM therapy can be triggered with PMA to exert enhanced lytic activity against MOPC-315 tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Antigens, Differentiation, T-Lymphocyte; CD8 Antigens; Cell Line; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Drug Synergism; Female; In Vitro Techniques; Ionomycin; Lymphocyte Depletion; Melphalan; Mice; Mice, Inbred BALB C; Phagocytes; Plasmacytoma; T-Lymphocytes; Tetradecanoylphorbol Acetate; Thymoma; Time Factors

Exposure of a myeloma cell line (RPMI 8226) to a 30-minute pulse of melphalan (1-phenylalanine-mustard) resulted in a cell cycle progression delay characteristic for DNA cross-linking agents. Reduction of outflow of cells from late S- and G2-phases was more pronounced as compared to that from G1-phase. The consequence is a progressive accumulation of cells in late S- and G2-phases. At restoration of outflow of cells from late S- and G2-phases, complete removal of DNA interstrand cross-links, as measured by DNA alkaline elution, was noted. At this time less than 50% of maximum DNA-protein cross-links were removed. Further we found no correlation between restored outflow of cells from the G2-phase and removal of DNA-protein cross-links during the follow-up time of 72 h. No DNA double strand breaks as measured by DNA neutral elution were formed during the observation period. The data suggest that removal of DNA interstrand cross-links seems prerequisite for the outflow of cells from G2 after melphalan treatment.

Topics: Cell Cycle; Cell Division; Cell Line; DNA Damage; DNA, Neoplasm; Dose-Response Relationship, Drug; Humans; Kinetics; Melphalan; Plasmacytoma; Time Factors

We reported previously that treatment of mice bearing MOPC-315 plasmacytoma with the drugs L-PAM (phenylalanine mustard) or 5-FU (5-fluorouracil), in combination with low doses of THF-gamma 2, was more effective in increasing their survival time than treatment with the drug alone. We show here that in the combined treatment using a single injection of 5-FU followed by multiple (8-15) injections of THF-gamma 2, the megadoses were more effective than the low doses in increasing the survival time of MOPC-315 tumor-bearing mice. On the other hand, in combination with L-PAM, both low and high doses of THF-gamma 2 were equally effective. The need for high doses of THF-gamma 2, when used in combination with 5-FU, could be due to the fact that 5-FU acts as a "non-immunomodulating" drug and has to be used at a high, immunosuppressive dose.

Topics: Animals; Cell Line; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorouracil; Immunotherapy; Melphalan; Mice; Mice, Inbred BALB C; Oligopeptides; Plasmacytoma; Thymus Hormones

Plasma cells derived from marrow aspirates of 21 untreated myeloma patients have been cultured in RPMI 1640 medium containing 3H-thymidine and melphalan. Thereafter plasma cell-labelling index was determined autoradiographically. In 20 patients melphalan caused a measurable decrease in the percentage of labelled plasma cells. Decreases in labelling index ranging from -4% to 3% have been considered as indicating the resistance of myeloma cells to melphalan in vitro. Decreases within this range have been found in 7 patients. In other 13 myelomas with chemosensitive marrow plasma cells, melphalan did reduce the labelling index to values ranging from 4% to 24%. Some clinical implications of the tests are discussed.

Topics: Adult; DNA, Neoplasm; Drug Resistance; Humans; In Vitro Techniques; Melphalan; Middle Aged; Plasma Cells; Plasmacytoma; Thymidine

We have previously demonstrated that depletion of CD8+ T-cells by the use of a monoclonal anti-Lyt-2.2 antibody abolishes the curative effectiveness of low-dose melphalan (L-phenylalanine mustard; L-PAM) therapy for BALB/c mice bearing a large (greater than or equal to 20 mm) s.c. MOPC-315 tumor and extensive metastases (Mokyr et al., Cancer Res., 49: 4597-4606, 1989). Here we show that as a consequence of low-dose L-PAM therapy, CD8+ T-cells accumulate in the s.c. tumor nodules of MOPC-315 tumor bearers. Specifically, an 80-fold increase in the number of CD8+ T-cells was seen within 5 days after the chemotherapy. Treatment of MOPC-315 tumor bearers with low-dose L-PAM in conjunction with monoclonal anti-Thy-1.2 or anti-Lyt-2.2 antibody, in contrast to treatment with monoclonal anti-L3T4 antibody, prevented the appearance of the massive CD8+ T-cell infiltrate in the s.c. tumor nodules. Fresh CD8+ T-cells derived from s.c. MOPC-315 tumor nodules that were regressing as a consequence of low-dose L-PAM therapy exhibited a potent direct lytic activity against the MOPC-315 plasmacytoma in a short-term in vitro assay. The specificity of the lytic activity exhibited by the CD8+ T-cells was illustrated not only by the inability of the CD8+ T-cells to lyse two antigenically unrelated thymomas (the WEHI 22.1 and the EL-4) and a natural killer-sensitive lymphoma (the YAC-1), but also by their relatively weak lytic activity against an antigenically related plasmacytoma (the MOPC-104E). Thus, CD8+ T-cells that infiltrate the s.c. tumor nodules of MOPC-315 tumor bearers following low-dose L-PAM therapy most likely exploit a CTL-type lytic mechanism to eradicate at least part of the large tumor burden not eliminated by the direct antitumor effects of the drug.

Topics: Animals; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; CD8 Antigens; Female; Immunohistochemistry; In Vitro Techniques; Lymphoma; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Plasmacytoma; T-Lymphocytes, Cytotoxic; Thymoma

BALB/c mice cured of large MOPC-315 plasmacytomas by melphalan remain deficient in their spleen T-cell functions. This was manifested by impairment of the allogeneic and the antibody responses in vitro to SRBC and in decreased numbers of T-cells including their subsets CD4 and CD8. IL-2 production and specific cytotoxicity against MOPC-315 tumor cells were, on the other hand, maintained. Treatment of these cured mice by in-vivo administration of THF-gamma 2, an octapeptide from calf thymus, repaired these deficits. This was evidenced by in vitro tests with spleen cells which manifested an increased allogeneic response and elevated generation of primary antibody response, restoration of T-cell subpopulations to normal and an enhanced IL-2 production above normal levels. The potential use of THF-gamma 2 as supportive therapy in cancer treatment is suggested.

Topics: Animals; Cytotoxicity Tests, Immunologic; Drug Evaluation, Preclinical; Erythrocytes; Flow Cytometry; Fluorescent Antibody Technique; Immunologic Deficiency Syndromes; Interleukin-2; Lymphocyte Culture Test, Mixed; Male; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Oligopeptides; Plasmacytoma; Spleen; Thymus Hormones

We have previously shown that, as a consequence of low-dose melphalan (L-phenylalanine mustard) treatment, thymocytes from mice bearing a large, day-10 MOPC-315 tumor, but not thymocytes from normal mice, acquire the ability to generate an enhanced level of antitumor cytotoxicity upon in vitro stimulation with MOPC-315 tumor cells plus low concentrations (9.0-90 IU/ml) of exogenous interleukin-2 (IL-2). Here we show that the time interval between tumor inoculation and low-dose melphalan therapy as well as the magnitude of tumor burden at the time of the chemotherapy are important for the ability of the drug to render thymocytes more responsive to in vitro stimulation with MOPC-315 tumor cells plus low concentrations of recombinant IL-2 (rIL-2). Specifically, the chemotherapy was found to be effective in enhancing the thymic antitumor reactivity only if the mice bore a large, late-stage tumor. Comparison of thymocytes from untreated mice bearing a large, late-stage tumor to thymocytes from normal mice revealed that tumor-bearer thymocytes contained approximately a three-fold higher frequency of cytotoxic T lymphocyte precursors (CTLp) for MOPC-315-associated antigens. Following curative low-dose melphalan therapy of mice bearing a large, late-stage MOPC-315 tumor, the frequency of CTLp for MOPC-315-associated antigens increased further, reaching a level approximately tenfold higher than that found among thymocytes of normal mice. At the same time, the frequency of CTLp for an antigenically unrelated allogeneic tumor (EL4) as well as the overall percentage of mature cells was not increased. The cells responsible for the exertion of the enhanced antitumor cytotoxicity following in vitro stimulation of thymocytes from mice treated with low-dose melphalan when they have a large, late-stage MOPC-315 tumor are of the CD8+/CD4- phenotype. Thus, the enhanced level of antitumor cytotoxicity generated by thymocytes from mice that are treated with low-dose melphalan when they have a large, late-stage MOPC-315 tumor is due, at least in part, to the presence of an enlarged pool of CTLp specific for MOPC-315-associated antigens, which mature into CD8+/CD4- effector cells upon stimulation with MOPC-315 tumor cells plus low concentrations of rIL-2.

Topics: Animals; Cell Survival; Dose-Response Relationship, Drug; Female; Interleukin-2; Lymphocyte Activation; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Phenotype; Plasmacytoma; T-Lymphocyte Subsets; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Thymus Gland; Time Factors

The effect of a synthetic thymic hormone, THF-gamma 2, on the anti-tumor activity of spleen cells was studied in mice immunized against the RPC-5 tumor. Following two courses of the THF-gamma 2 treatment, the mean RPC-5 specific cytotoxic response of immune spleen cells was significantly increased when compared to normal cells (P less than 0.001) and to untreated immune spleen cells (P less than 0.04). In addition, THF-gamma 2 treatment improved the competence of immune spleen cells in adoptive immunotherapy (AIT) when performed in combination with chemotherapy by melphalan. Recipients of spleen cells from THF-gamma 2 treated mice showed a 35% increase in survival when compared to AIT with immune cells alone. The results suggest that THF-gamma 2 treatment of donors for AIT might be applicable to cancer therapy in humans.

Topics: Animals; Combined Modality Therapy; Cytotoxicity, Immunologic; Immunotherapy; Male; Melphalan; Mice; Mice, Inbred BALB C; Oligopeptides; Plasmacytoma; Spleen; Thymus Hormones

We have previously shown that spleen cells from BALB/c mice that are in the process of eradicating a large MOPC-315 tumor following low-dose (2.5 mg/kg) melphalan (L-phenylalanine mustard) therapy are effective in preventing tumor progression upon adoptive transfer into BALB/c mice bearing a barely palpable tumor that had been treated with a subcurative dose of melphalan [Mokyr et al. (1989) Cancer Res 49:4597]. Here we show that such spleen cells in conjunction with a subcurative dose of drug (adoptive chemoimmunotherapy, ACIT) can cause the complete regression of a large (15-20 mm) s.c. MOPC-315 tumor in a large percentage of T-cell-deficient (athymic nude) tumor-bearing mice. Spleen cells that were effective in ACIT of athymic nude mice displayed in vitro a substantial direct lytic activity against MOPC-315 tumor cells, and the lytic activity was greatly enhanced when the spleen cells were cultured for 5 days with or without mitomycin-C-treated MOPC-315 stimulator tumor cells. The cells responsible for the therapeutic effectiveness of the spleen cells in ACIT of athymic nude mice, as well as the cells responsible for the direct in vitro anti-MOPC-315 lytic activity of the spleen cells, were of the Lyt 2 and not the L3T4 phenotype. Most of the athymic nude mice that completely eradicated a large MOPC-315 tumor as a consequence of ACIT were capable of rejecting a challenge with 30-100 times the minimal lethal tumor dose for 100% of normal BALB/c mice administered more than 1 month after the ACIT. The ability of these athymic nude mice to resist the tumor challenge was associated with the presence of a greatly elevated percentage of cells expressing T cell surface markers in their spleens. Thus, it is conceivable that splenic Lyt 2+T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor mediate their therapeutic effectiveness in ACIT of athymic nude mice bearing a large MOPC-315 tumor, at least in part, through direct cytotoxicity for MOPC-315 tumor cells. In addition, eradication of a large MOPC-315 tumor through cooperation between antitumor immunity and melphalan toxicity endues the athymic nude mice with an elevated percentage of T cells in their secondary lymphoid organs, and these T cells are probably responsible for the long-lasting protective antitumor immunity exhibited by these mice.

Topics: Animals; Antigens, Differentiation, T-Lymphocyte; Combined Modality Therapy; Dose-Response Relationship, Drug; Immunization, Passive; Immunotherapy; Melphalan; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental; Plasmacytoma; Spleen; Survival Analysis; T-Lymphocytes

We have previously demonstrated that the curative effectiveness of a low dose (2.5 mg/kg) of melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large s.c. (approximately 20 mm in diameter) MOPC-315 tumor and extensive metastases requires the participation of T-cell-dependent antitumor immunity in tumor eradication (S. Ben-Efraim et al., Cancer Immunol. Immunother., 15: 101-107, 1983). Here we show that the Lyt 2+ T-cells, and not the L3T4+ T-cells, participate in the cure of such tumor-bearing mice by a low dose of L-PAM. Specifically, depletion of Lyt 2+ T-cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal anti-Lyt 2.2 antibody abolished the curative effectiveness of the low dose of drug. In contrast, depletion of L3T4+ T-cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal anti-L3T4 antibody did not reduce significantly the curative effectiveness of the low dose of drug. Histological examination of tumor nodules on various days following low-dose L-PAM therapy revealed widespread lymphocytic infiltration by Day 5 following the chemotherapy, and this infiltration was drastically reduced when the L-PAM-treated tumor bearers were treated with either anti-Thy 1.2 or anti-Lyt 2.2 antibody but not with anti-L3T4 antibody. The antitumor immunity exhibited by Lyt 2+ T-cells derived from mice which were in the process of eradicating a large MOPC-315 tumor following low-dose L-PAM therapy was exploited successfully to confer systemic antitumor immunity to mice bearing a barely palpable tumor. Specifically, the adoptively transferred Lyt 2+ splenic T-cells, in conjunction with a subcurative dose of L-PAM, brought about the cure of most mice. The Lyt 2+ splenic T-cells from L-PAM-treated MOPC-315 tumor bearers were also found to be capable of exerting a direct potent lytic effect against MOPC-315 tumor cells in an antigen-specific manner. Thus, it is conceivable that the direct cytotoxic activity of Lyt 2+ T-cells for MOPC-315 tumor cells is responsible, at least in part, for the ability of the Lyt 2+ T-cells from L-PAM-treated MOPC-315 tumor bearers to bring about the eradication of the tumor burden not eradicated through the direct antitumor effects of the low dose of drug.

Topics: Animals; Antigens, Surface; Cell Line; Cell Movement; Female; Isoantibodies; Lymphocyte Depletion; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Spleen; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Thy-1 Antigens

We have previously shown that enhanced antitumor cytotoxicity is generated when thymocytes from melphalan (L-phenylalanine mustard; L-PAM)-treated MOPC-315 tumor bearers, but not thymocytes from normal mice, are added to the immunization culture of syngeneic normal spleen cells and MOPC-315 tumor cells (Bartik et al., Cancer Res., 47: 4848-4855, 1987). Here we show that normal spleen cells produce, upon stimulation with MOPC-315 tumor cells, helper-like factors which are sufficient for thymocytes from L-PAM-treated MOPC-315 tumor bearers, but not for thymocytes from normal mice, to develop antitumor cytotoxicity in response to stimulation with MOPC-315 tumor cells. Since one of the helper-like factors produced by in vitro-immunized spleen cells is interleukin 2 (IL-2), we assessed the exogenous IL-2 requirements for the development of anti-MOPC-315 cytotoxicity in thymocytes from L-PAM-treated MOPC-315 tumor bearers, relative to thymocytes from normal mice. Thymocytes from L-PAM-treated MOPC-315 tumor bearers were found to require a 10-fold lower concentration of recombinant IL-2 (rIL-2) than thymocytes from normal mice in order to develop antitumor cytotoxicity in response to stimulation with MOPC-315 tumor cells. The concentration of rIL-2 required for the development of anti-MOPC-315 cytotoxicity by thymocytes from L-PAM-treated MOPC-315 tumor bearers was also 10-fold lower than the concentration of rIL-2 required by thymocytes from untreated MOPC-315 tumor bearers or thymocytes from L-PAM-treated normal mice. In addition, at any concentration of rIL-2 employed, thymocytes from L-PAM-treated MOPC-315 tumor bearers developed a higher level of anti-MOPC-315 cytotoxicity than did thymocytes from normal mice, L-PAM-treated normal mice, or untreated MOPC-315 tumor bearers. The enhanced antitumor cytotoxicity exhibited by thymocytes from L-PAM-treated MOPC-315 tumor bearers, following in vitro stimulation with MOPC-315 tumor cells plus rIL-2, was evident not only against MOPC-315 tumor cells but also against other syngeneic plasmacytomas but not an allogeneic thymoma. In addition, thymocytes from L-PAM-treated MOPC-315 tumor bearers required less rIL-2 than thymocytes from normal mice to develop antitumor cytotoxicity in response to stimulation with MOPC-315-associated antigens but not in response to stimulation with an allogeneic antigenically unrelated thymoma (EL4).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Cell Line; Cytotoxicity, Immunologic; Female; Interleukin-2; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Recombinant Proteins; T-Lymphocytes

Mice cured from large MOPC-315 tumors by a single dose of melphalan, 7.5 mg/kg, were examined for up to 60 days after the drug treatment (71 days after the tumor inoculation) for their ability to respond to mitogenic stimulation, specific and nonspecific antigenic stimulation and for their susceptibility to inoculation with an unrelated tumor, L10 lymphoma. The response of spleen cells from cured mice to mitogenic stimulation by phytohemagglutinin or concanavalin A was slightly depressed at an early stage after the drug treatment. The allogeneic response against C57BL spleen cells and the antibody response against sheep red blood cells (SRBC) of spleen cells from cured mice remained below normal levels during the whole observation period. The deficiency in response to antigenic stimulation was found to be due to impairment in T-cell function. Cured mice were also deficient in their response to SRBC immunization (antibody and delayed-type hypersensitivity responses) and were more susceptible to inoculation with an unrelated tumor, L10 lymphoma, than normal, noninoculated mice. On the other hand, spleen cells of cured mice developed a highly specific cytotoxic response against target MOPC-315 tumor cells and the cured mice were resistant to challenge with an otherwise highly tumorigenic dose of MOPC-315. Thus, cured mice remained deficient for a long period of time in their response to MOPC-315-unrelated antigens but, at the same time, they showed a potent specific antitumor immunity potential in vivo and in vitro.

Topics: Animals; Antibody Formation; B-Lymphocytes; Cytotoxicity, Immunologic; Dose-Response Relationship, Immunologic; Hypersensitivity, Delayed; Immunity; Lymphocyte Activation; Lymphoma; Melphalan; Mice; Mitogens; Plasmacytoma; Spleen; T-Lymphocytes

We have previously shown that mice cured of a large MOPC-315 tumor following low-dose melphalan (L-phenylalanine mustard, L-PAM) therapy can exert, upon challenge with MOPC-315 tumor cells, an antitumor effect against innocent bystander tumor cells present within the same tumor site (Barker, E., and Mokyr, M.B. Cancer Immunol. Immunother., 25: 215-224, 1987). Here we show that T-cells are important for the MOPC-315-induced rejection of MOPC-104E tumor cells present within the same site. To further characterize the innocent bystander killing activity exerted by L-PAM-cured MOPC-315 tumor bearers upon stimulation with MOPC-315 tumor cells, we established the in vitro conditions under which lymphoid cells from L-PAM-cured MOPC-315 tumor bearers can exert an antitumor effect against innocent bystanders. Specifically, we established that spleen cells from mice that just completed the rejection of a large MOPC-315 tumor following low-dose L-PAM therapy can, upon stimulation with MOPC-315 tumor cells, bring about the killing of antigenically unrelated tumor cells in a 12-h 51Cr release assay. The magnitude of lysis of EL4 and WEHI 22.1 tumor cells by MOPC-315 in vitro-immunized (IVI) spleen cells from L-PAM-cured MOPC-315 tumor bearers can be substantially enhanced upon reexposure of the spleen cells to MOPC-315-associated antigens during the 12-h 51Cr release assay. The lysis of innocent bystander tumor cells by these MOPC-315-IVI spleen cells was found to be mediated by T-cells of the Lyt 2 and not the L3T4 phenotype. These Lyt 2+ T-cells did not appear to mediate their lytic activity for innocent bystander tumor cells via effector macrophages, since a drastic reduction in macrophage frequency among the MOPC-315-IVI spleen cells just prior to assessing the lytic activity of the spleen cells did not reduce, but actually enhanced, the magnitude of EL4 lysis. In addition, a Lyt 2+ T-cell clone derived from mice cured of a large MOPC-315 tumor by a low dose of drug was capable, upon stimulation with MOPC-315 tumor cells, of exerting a potent lytic effect against EL4 and WEHI 22.1 tumor cells in the 12-h 51Cr release assay. Thus, Lyt 2+ T-cells independent of effector macrophages are responsible for lysis of innocent bystander tumor cells by MOPC-315-IVI spleen cells from L-PAM-cured MOPC-315 tumor bearers.

Topics: Animals; Cell Line; Cytotoxicity, Immunologic; Isoantibodies; Macrophages; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Reference Values; Spleen; T-Lymphocytes; T-Lymphocytes, Cytotoxic

The effectiveness of a relatively low dose of cyclophosphamide (15 mg/kg CY), melphalan (2.5 mg/kg L-PAM) or the monofunctional form of CY (150 mg/kg MoCY) for the cure of mice bearing a large primary s.c. MOPC-315 tumor and extensive metastases has been shown to be dependent on the cooperation of the drugs' tumoricidal activity with T-cell-dependent antitumor immunity, the latter facilitated by the drug's immunomodulatory activity. Here, we have compared the curative effectiveness of three additional drugs: methyl nitrosourea (MNU), hydroxyurea (OH-urea) and bis-chloroethyl nitrosourea (BCNU). Among these drugs, only a relatively low dose of BCNU (15-20 mg/kg) was effective in curing most mice (85%) bearing a large, late stage tumor. A higher dose of BCNU (40 mg/kg, LD10) was much less effective. After an optimal dose of BCNU, the proliferative capacity of the tumor cells 24 h after therapy was reduced by greater than 97%. However, viable tumorigenic cells were still present in the primary tumor and enhanced T-cell-dependent antitumor immunity was necessary for their eradication. The cured mice were resistant to tumor rechallenge. When a low curative dose of L-PAM was followed by OH-urea, the therapeutic effectiveness was not affected, but when this dose of L-PAM was followed by a high nontoxic dose of MNU (100-150 mg/kg), the therapeutic effectiveness was diminished even though MNU was highly tumoricidal (i.e. greater than 99% inhibition of proliferative activity). Thus, BCNU appears to be similar to CY, L-PAM and MoCY in its mechanism of MOPC-315 tumor eradication. The alkylating activity of CY, L-PAM, MoCY and BCNU appears to be critical for their combined tumoricidal and immunomodulatory effects. Since BCNU is the simplest of these four drugs with respect to metabolic pathway, a further study with BCNU and related constructs may shed some light on the biochemical mechanisms of their mode of action. At least one reason for the ineffectiveness of OH-urea or MNU at either low or nontoxic high doses was poor tumoricidal or immunomodulatory activity, respectively. Thus, it seems important to consider both the tumoricidal and immunomodulatory activities of drugs when developing regimens for effective chemotherapy.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; Carmustine; Cell Division; Cyclophosphamide; Female; Hydroxyurea; Immunity; Melphalan; Methylnitrosourea; Mice; Mice, Inbred BALB C; Plasmacytoma; Spleen

Alkylating agents can cause latent and permanent damage to the bone marrow. We compared the long term effects of melphalan on a number of immune and haemopoietic functions of plasmacytoma bearing BALB/c mice with that of normal mice treated with a similar dose of melphalan. The drug administered orally at a dose of 250 micrograms and 400 micrograms on day 14 and 24 following i.m. inoculation of MOPC-315 plasmacytoma cells resulted in cure of the mice. Their spleen cells showed a permanent impairment of MLR activity, T-cell number and IL-2 production as well as a mild suppression of NK activity for one year after cessation of melphalan therapy. The number of B cells was elevated. In contrast, plasmacytoma-free mice treated with melphalan retained long term normal immune functions, although shortly after melphalan therapy a temporary suppression was noted. On the other hand, melphalan was responsible for bone marrow myeloid stem cell damage since the number of myeloid progenitor cell (CFU-GM) colonies was reduced in both melphalan-treated groups compared to untreated normal controls. Plasmacytoma bearing mice had a shorter survival. These results demonstrate that some late sequelae of alkylating agents are not due to the drug alone; shorter survival and T-cell deficiency are related to the previous presence of the tumour.

Topics: Animals; B-Lymphocytes; Female; Hematopoietic Stem Cells; Killer Cells, Natural; Leukocyte Count; Lymphocytes; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; T-Lymphocytes

It is reported on the treatment of three patients with a hyperviscosity syndrome in IgG-plasmocytoma. Before every polychemotherapy cycle a plasma exchange was carried out, when the total protein in the serum and the immunoglobulins were essentially increased and clinical symptoms of the hyperviscosity syndrome were existing. The results and the possible effects on the efficacy of the therapy with cytostatic agents are discussed. In the light of our experiences we can recommend the membrane plasma filtration treatment as symptomatic therapeutic measure in the hyperviscosity syndrome.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Viscosity; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Male; Melphalan; Middle Aged; Plasma Exchange; Plasmacytoma; Prednisone; Syndrome; Vincristine

Topics: Animals; Hematopoietic Stem Cells; Leukemia, Myeloid, Acute; Melphalan; Mice; Mice, Inbred BALB C; Neoplasms, Multiple Primary; Plasmacytoma

An 81-year-old man presented with bilateral orbital tumors that were found to be extramedullary plasmacytomas. Immunoperoxidase staining of the tissue was positive for IgG-kappa; no lambda chains were seen. Results of serum immunoelectrophoresis were positive for monoclonal IgG-kappa. Test results of the urine were positive for Bence Jones protein; only kappa chains were seen on radial diffusion. Systemic evaluation failed to show tumor elsewhere. The patient was treated with radiation and low-dose melphalan/prednisone, with good response. Five years later, the results of immunoelectrophoresis are normal and there is no clinical evidence of tumor; however, a small amount of kappa light chains remains in the urine. This case supports the important therapeutic and prognostic differences among orbital involvement in extramedullary plasmacytoma, solitary myeloma of bone, and multiple myeloma.

Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Humans; Male; Melphalan; Orbital Neoplasms; Plasmacytoma; Prednisone; Tomography, X-Ray Computed

BALB/c mice cured of a large MOPC-315 or MOPC-104E plasmacytoma following treatment with a low dose (2.5 mg/kg) of melphalan (L-PAM) were resistant to challenge with the other plasmacytoma but to a much lesser extent than to challenge with the autochthonous plasmacytoma. The resistance of the L-PAM-cured MOPC-315-tumor bearers to challenge with MOPC-104E tumor cells was increased when the MOPC-104E tumor cells were admixed with MOPC-315 tumor cells prior to their inoculation. This enhanced resistance to MOPC-104E cells was due to elimination of the MOPC-104E tumor cells through an innocent bystander killing effect since it did not render the mice more resistant to a subsequent challenge with MOPC-104E tumor cells alone. Administration of carrageenan to L-PAM-cured MOPC-315-tumor bearers 1 day after the challenge with the mixture of MOPC-104E and MOPC-315 tumor cells drastically reduced the ability of the mice to resist the tumor challenge. All of the tumors that developed in such mice were of MOPC-104E origin only (as judged by the binding specificity of the myeloma proteins secreted by the tumor cells as well as that present on their surface) even though (a) the tumor inoculum used consisted of up to 10-fold more MOPC-315 than MOPC-104E tumor cells and (b) the MOPC-315 tumor cells divide more rapidly. The same protocol of carrageenan treatment did not reduce the ability of normal BALB/c mice to develop in vivo a primary cell-mediated cytotoxic response nor a primary antibody response indicating that it has no effect on the initiation of an immune response. Therefore, it is conceivable that carrageenan treatment reduced the ability of L-PAM-cured MOPC-315-tumor bearers to reject a challenge with MOPC-315 and MOPC-104E tumor cells by interfering at the effector stage. The ability of the L-PAM-cured MOPC-315-tumor bearers to reject the MOPC-315 cells present in the challenge mixture was reduced when the mice were treated with anti-Thy 1.2 antibody but not with carrageenan, indicating that T-cells independent from carrageenan-sensitive effector cells are required for the rejection of the MOPC-315 tumor cells. Thus, at least two different effector mechanisms participate in the rejection of a challenge composed of MOPC-315 and MOPC-104E tumor cells by L-PAM-cured MOPC-315-tumor bearers.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Carrageenan; Depression, Chemical; Female; Graft Rejection; Immunity, Cellular; Immunity, Innate; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmacytoma; Thymoma; Thymus Neoplasms

In a human case of plasmacytoma we studied plasma and tumor concentrations of melphalan given intravenously. Intratumoral concentration of melphalan was similar to plasma concentration 60 min after the end of infusion.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Injections, Intravenous; Male; Melphalan; Oropharyngeal Neoplasms; Pharyngeal Neoplasms; Plasmacytoma; Prednisolone

The anticancer chemotherapeutic drugs melphalan (L-phenylalanine mustard; L-PAM), 5-fluorouracil (5-FU), methotrexate (MTX), and daunorubicin (DAU) were tested for their toxic activity against MOPC-315 tumor cells in vitro. L-PAM, 5-FU, and DAU had a marked toxic effect whereas MTX did not affect the rate of thymidine incorporation in the tumor cells. L-PAM (7.5 mg/kg) induced permanent regression of large s.c. MOPC-315 plasmacytoma tumors, 5-FU (200-250 mg/kg) induced transient regression of MOPC-315 tumors with reappearance starting on the 6th day after the 5-FU injection and DAU (5 mg/kg) was not effective. L-PAM treatment restored the cytotoxic potential of spleen cells of tumor-bearing mice against target MOPC-315 tumor cells whereas spleen cells from tumor-bearing mice treated with 5-FU were unable to mount a cytotoxic response. L-PAM and 5-FU were also assayed for their effect in vitro on induction of suppressor T cells by ConA. L-PAM treatment in vitro markedly reduced the induction of suppressor T cells by ConA whereas 5-FU had no effect. It is suggested that anticancer chemotherapeutic drugs can be classified in "immunopromoting" (L-PAM as prototype) and "nonimmunopromoting" (5-FU as prototype) on the basis of their effect in vivo on established tumors and their effect on induction of suppressor T cells by ConA.

Topics: Adjuvants, Immunologic; Animals; Concanavalin A; Cytotoxicity, Immunologic; Fluorouracil; Lymphocyte Activation; Melphalan; Mice; Mice, Inbred BALB C; Myeloma Proteins; Phytohemagglutinins; Plasmacytoma; Spleen; T-Lymphocytes, Regulatory

Topics: Aged; Biopsy; Bone Marrow; Bone Neoplasms; Clavicle; Diagnosis, Differential; Female; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasma Cells; Plasmacytoma

We report in a 40 year-old woman a bifocal mammary and vertebral plasmocytoma attended by surgery and "preventive" chemotherapy. Eight years later, an acute and apparently non secondary myeloblastic leukemia is observed without sign of diffuse myelomatosis. Plasma cell tumors of the breast are uncommon. Eleven cases have been published, combining solitary plasmocytoma and infiltration occurring in multiple myeloma.

Topics: Adult; Breast Neoplasms; Female; Humans; Leukemia, Myeloid, Acute; Melphalan; Neoplasms, Multiple Primary; Plasmacytoma; Spinal Neoplasms; Time Factors

We have shown previously that low-dose melphalan (L-PAM) therapy of mice bearing a large MOPC-315 plasmacytoma enables their hitherto immunosuppressed spleen cells to exert potent anti-MOPC-315 cytotoxicity following in vitro immunization with MOPC-315 tumor cells. Here we show that, following in vitro immunization with MOPC-315 tumor cells, spleen cells from such L-PAM-treated MOPC-315 tumor bearers exhibited enhanced T-cell-mediated cytotoxicity not only against the MOPC-315 tumor, but also against another plasmacytoma (MOPC-104E) possessing surface immunoglobulin (SIg) of a different idiotype than the MOPC-315 cells, as well as against a variant of the MOPC-315 tumor which does not produce nor possess SIg (SIg- MOPC-315). The enhanced cytotoxicity was directed against target antigens which are not expressed on the surface of the syngeneic WEHI 22.1 thymoma or the natural killer-sensitive YAC-1 cells. Plasmacytoma shared antigens, other than immunoglobulins, were able to stimulate spleen cells from L-PAM-cured MOPC-315 tumor bearers to generate in vitro a secondary type anti-plasmacytoma cytotoxic response. L-PAM-cured MOPC-315 tumor bearers exhibited in vivo immunity against SIg- MOPC-315 tumor cells, which was sufficiently triggered by the SIg- cells to bring about the rejection of a challenge of at least 100-fold the minimal lethal tumor dose of the SIg- MOPC-315 cells. Thus, SIg- MOPC-315 tumor cells present among SIg+ tumor cells in the parental MOPC-315 tumor inoculum can be eradicated in the L-PAM-treated MOPC-315 tumor bearers by the immune response to SIg+ tumor cells as well as by the immune response to SIg- tumor cells themselves.

Topics: Animals; Antibody Specificity; Antigens, Neoplasm; Cell Line; Cytotoxicity, Immunologic; Female; Immunocompetence; Lymphocyte Depletion; Macrophages; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Spleen; T-Lymphocytes; Thymoma

Twenty-one patients with alkylator-resistant plasmacell neoplasms were treated with Peptichemio (PTC) at a dose of 40 mg/m2 for 3 days every 3 weeks or, in the case of persistent leukopenia and/or thrombocytopenia, at the single dose of 70 mg/m2 every 2-3 weeks according to haematological recovery. Seventeen patients, 10 with multiple myeloma and seven with extramedullary plasmacytoma (EMP), were fully evaluable. Six of 17 patients (35%) responded: three of seven EMP patients had a complete remission and 3 of 10 multiple myeloma patients had an objective response greater than 50%. The median duration of response was 8.5 months. An EMP patient obtained a complete response lasting for 16 months. The most frequent toxic effect were phlebosclerosis, occurring in all the patients, and myelosuppression, which was severe in only one case. PTC appears to be an active drug in patients with plasmacell neoplasms even if resistant to alkylating agents.

Topics: Adult; Aged; Alkylating Agents; Bone Marrow; Drug Resistance; Humans; Melphalan; Middle Aged; Multiple Myeloma; Peptichemio; Phlebitis; Plasmacytoma

Topics: Adjuvants, Immunologic; Animals; Cytotoxicity, Immunologic; Drug Administration Schedule; Immunity, Innate; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmacytoma; Spleen; T-Lymphocytes, Regulatory; Time Factors

BALB/c mice inoculated with MOPC-315 tumor cells developed an antiviral response against C-type particles extracted from subcutaneous tumors of plasmacytoma-bearing mice as shown by in vitro stimulation of spleen cells from tumor-bearing mice by virus-containing preparations. Induction of blastogenic response by virus-containing preparations was found to occur in unfractionated spleen cell populations, the glass-wool non-adherent fraction (depleted of macrophages and tumor cells) and the nylon-wool non-adherent (T-enriched) fraction of spleen cells. The antiviral response was no more detectable in spleens of tumor-bearing mice cured by melphalan. Cured mice developed a strong antitumor immune response as shown by their resistance to challenge with a tumorigenic dose of MOPC-315 tumor cells. However, challenge with tumor cells of cured, resistant mice did not induce reappearance of antiviral response.

Topics: Animals; Immunity, Cellular; In Vitro Techniques; Lymphocyte Activation; Male; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma; Retroviridae; Spleen; Time Factors

As previously reported, tumor-bearing BALB/c mice can be cured by split-course melphalan therapy, with 40-60% of the treated animals developing resistance to subsequent challenge with viable MOPC-315. The present study deals with the identification of effector-cytotoxic cells that may be developed as a result of chemotherapy-induced tumor regression and their possible potentiation by active, specific immunization with melphalan- and glutaraldehyde-treated MOPC-315 plasmacytoma cells. The cytotoxic potential of spleen-derived lymphocytes in treated animals could be demonstrated only after in vitro sensitization against mitomycin-treated MOPC-315 cells. Lymphocyte-mediated cytotoxicity, as measured against syngeneic 51Cr-labeled MOPC-315, could be detected in melphalan-cured animals and was significantly enhanced by active immunization as compared to the cytotoxicity seen in normal and tumor-bearing mice. With the use of M109 syngeneic, unrelated tumor cells as control targets in the assay, no cytotoxicity was detected. Macrophage cytotoxicity was not significantly enhanced in any of the treatment groups described, with these assays performed 6-8 weeks following treatment and cure. When in vitro killing of MOPC-315 targets was tested with the use of peritoneal macrophages harvested shortly following cure of ascitic tumor by ip injected melphalan, the cytotoxic response was significantly enhanced. In conclusion, following chemotherapy-mediated cure of established MOPC-315 tumors, splenic lymphocytes exhibited enhanced antitumor cytotoxicity, which was further augmented by active immunization. Macrophage activation, as measured by direct cytotoxicity against MOPC-315 targets, was found to occur locally and early following the event of melphalan-induced tumor regression.

Topics: Animals; Cytotoxicity, Immunologic; Immunization; Immunotherapy; In Vitro Techniques; Lymphocytes; Macrophages; Melphalan; Mice; Mice, Inbred BALB C; Plasmacytoma

Topics: Bone Neoplasms; Combined Modality Therapy; Diabetic Neuropathies; Diagnosis, Differential; Humans; Ischium; Male; Melphalan; Middle Aged; Osteolysis; Plasmacytoma; Polyneuropathies; Tomography, X-Ray Computed

A sarcolysine-resistant strain of mouse plasmacytoma MOPC/406 was obtained in experiments on 250 BALB/c mice. The initial plasmacytoma strain is highly sensitive to sarcolysine. When administered in doses of 10 and 5 mg/kg it increases the lifespan up to 50 days (the observation period). In the course of resistance induction by incremental doses of sarcolysine, a highly resistant plasmacytoma strain was obtained. In the 20th generation of inoculations with the use of sarcolysine administration of 10 mg/kg (intraperitoneally) provided only a 18% increase in the lifespan, whereas the dose 5 mg/kg stimulated the growth of plasmacytoma. The strain obtained preserves its resistance under cryoconservation in liquid nitrogen, being a model that permits one to study resistance, cross-resistance and approaches to its overcoming.

Topics: Animals; Cell Line; Drug Evaluation, Preclinical; Drug Resistance; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmacytoma

The growth curve of monolayer cultures of ARH-77 cells, a human myeloma cell line propagated in vitro, is represented by an everbending curve on a semilogarithmic plot; however, the curve can be fitted by a straight line on a linear-linear plot. This unusual growth pattern suggests that, instead of a fixed proportion of the population, a fixed number of ARH-77 cells divide per unit time. The following are cell cycle transit time parameters calculated from percent labeled mitosis experiments: TG1, 10.0 +/- 3.5 hours; Ts, 14.3 +/- 2.3 hours; TG2, 4.3 hours; TM, 1.4 +/- 1.3 hours; and Tc, 30.0 +/- 6.1 hours. For cells exposed continuously to 3H-thymidine the values are: growth fraction, 67%; TG1, 6.5 hours; Ts, 13.0 hours; and TG2 + M, 3.0 hours. The average doubling time is 4.6 days (range, 3.8-4.7 days); after about 10 to 15 days in culture, the growth rate of freshly passaged cells declines markedly, as reflected by a growth curve with a much shallower slope. The changes are accompanied by a marked decline in the labeling index from 41.3% (range, 28.9%-53.7%) during the first 3 days of culture to less than 5% measured on day 21. Flow cytometry for DNA content-dependent cell cycle compartment distribution demonstrates an obvious decline in the proportion of S-phase cells and a marked accumulation of G2 phase cells as the cultures age. When the supernatant medium of ARH-77 cells grown for 10 days is replaced by fresh medium, a new burst of vigorous cellular growth is observed with a curve slope similar to that observed during the first 5 days of culture. If the 10-day-old supernatant medium is used to set up cultures with freshly harvested ARH-77 cells, their growth curve resembles that of 10-day-old cultures. However, this supernatant medium induces no decrease in the growth rate of other human tumor cells, suggesting that inhibition of cellular growth does not result from exhaustion of nutrients, but that ARH-77 cells produce a molecular mediator that specifically inhibits the growth of these cells. ARH-77 cells could be synchronized with a single treatment of 3 or 5 mM thymidine; (dThd) and cloning efficiency was 2% to 4% in a double-layer soft agar assay. Treatment for 1 hour with increasing concentrations of melphalan produced a threshold exponential survival curve (Dq = 0.45 microgram/ml and D0 = 0.35 microgram/ml, 1 hour).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Animals; Cell Cycle; Cell Line; Cell Survival; Clone Cells; Female; Growth Inhibitors; Humans; Melphalan; Mice; Mice, Nude; Neoplasm Transplantation; Plasmacytoma; Transplantation, Heterologous

Topics: Chlorambucil; Cyclophosphamide; Drug Therapy, Combination; Humans; Hypergammaglobulinemia; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Orthopedic Equipment; Paraproteins; Plasmacytoma; Prednisone; Prognosis; Vincristine; Waldenstrom Macroglobulinemia

An asymptomatic multiple myeloma of the kappa-light chain type was found in a patient with nephrotic syndrome and renal insufficiency. Light microscopy showed nodular glomerulosclerosis of the kidney similar to diabetic glomerulosclerosis. Diabetes mellitus could not be demonstrated. kappa-Light chain deposits could be shown by immunohistology in the mesangium and the glomerular and tubular basal membrane. In addition, massive kappa-light chain deposits in the sinusoidal walls of the liver and at the dermoepidermal junction of the skin and in the corium were found.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Bone Marrow Cells; Carmustine; Cyclophosphamide; Humans; Hypergammaglobulinemia; Hypertension, Renal; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Plasma Cells; Plasmacytoma; Prednisone; Vincristine

Administration of a low dose of L-PAM (0.75 mg/kg) to mice bearing a large SC MOPC-315 tumor and extensive metastases led to the development of augmented antitumor immune potential in their hitherto immunosuppressed spleen cells. Such drug-induced potentiation of antitumor immune responsiveness appeared by day 2 after chemotherapy, and it could not be further enhanced but was actually reduced by depletion of glass-adherent cells, a procedure which is effective in depleting the cells known to have inhibitory activity (i.e., macrophages and metastatic tumor cells). To establish that L-PAM can lead to selective in situ abrogation of the inhibitory effectiveness of the splenic macrophages and metastatic tumor cells, we demonstrated that incubation of immunosuppressed tumor-bearer spleen cells with a low concentration of L-PAM in vitro also resulted in augmented antitumor immune potential that could not be further augmented by depletion of glass-adherent cells. L-PAM-mediated enhancement of the antitumor immune potential of immunosuppressed tumor bearer spleen cells was due at least in part to the effects of the drug on the splenic metastatic tumor cells. Isolated tumor cells treated with a low concentration of L-PAM were not only devoid of inhibitory activity for the primary in vitro antitumor immune response by normal spleen cells, but actually manifested a strong immunostimulatory capacity. Thus, L-PAM given at a low dose enhances the development of potent antitumor immunity which brings about the eradication of a large tumorigenic load that remains after the drug has been cleared from the circulation.

Topics: Animals; Antibiotics, Antineoplastic; Cell Line; Cytotoxicity, Immunologic; Female; Immunosuppression Therapy; Immunotherapy; Lymphocytes; Melphalan; Mice; Mice, Inbred BALB C; Mitomycin; Mitomycins; Plasmacytoma; Spleen

Topics: Animals; Colonic Neoplasms; Cyclophosphamide; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Gastric Mucosa; Male; Melphalan; Plasmacytoma; Prednisone; Stomach Neoplasms

Following inoculation with 1 X 10(6) MOPC-315 tumor cells, a single injection of a very low dose of melphalan (L-PAM, L-phenylalanine mustard), 0.75 mg/kg, cured most of the mice bearing a day 11 large primary tumor (20 mm) and metastases, but failed to cure mice bearing a day 4 nonpalpable tumor. Treatment of mice bearing a nonpalpable tumor with the very low dose of drug compromised the ability of the mice to respond effectively to the same low dose of drug when the tumor became large (day 12). However, a nonpalpable tumor could be eradicated by treatment of tumor bearers with a low dose of L-PAM, if it was present concomitantly with a large tumor on the contralateral side. A high dose of L-PAM, 15 mg/kg, cured mice bearing either a nonpalpable or a large tumor. The eradication of the tumor induced by the high dose of L-PAM appeared to be due solely to the tumoricidal effect of the drug. On the other hand, the eradication of the tumor by the low dose of L-PAM also required the participation of antitumor immunity of the host, since subsequent injection of antithymocyte serum abrogated the curative effect of the drug in most mice. Mice cured by a high dose of L-PAM were not resistant to subsequent lethal tumor challenge. In contrast, mice cured by the low dose of L-PAM were able to reject a tumor challenge of 300 times the minimal lethal tumor dose. The results obtained with L-PAM therapy are similar to the results that we had previously reported with cyclophosphamide therapy. Thus, the timing of therapy with a low dose of drug for mice bearing a MOPC-315 tumor is critical for successful therapy. Moreover, the selection of a low dose rather than a high dose of drug to eradicate a large tumor offers the advantage that it results in long-lasting potent antitumor immunity as a consequence of the participation of host antitumor immunity in the eradication of the tumor.

Topics: Animals; Cell Division; Cell Line; Cell Survival; Kinetics; Melphalan; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Plasmacytoma

The most common side effects of melphalan administration include nausea, vomiting, and bone marrow suppression. Less well known is the fact that allergic reactions can become evident after both intravenous and oral melphalan administration. In the present study we report a patient with a plasmocytoma, who developed an allergic reaction with melphalan intravenously, but tolerated melphalan orally.

Topics: Drug Hypersensitivity; Drug Therapy, Combination; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin M; Male; Melphalan; Middle Aged; Plasmacytoma; Vincristine

Chemotherapy with alkylating agents and Prednisone can achieve a prolonged median survival time in patients with multiple myeloma which lasts as long as the remission endures. Aggressive therapeutic regimens could not achieve a further tumor cell reduction as soon as a stable phase is reached. Waldenström's macroglobulinemia requires a therapeutic approach, which is adjusted to the individual case. Patients with small tumor mass and therapy responders have a significant prolonged median survival time compared to patients with large tumor mass and non-responders.

Topics: Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunoglobulin Fragments; Immunoglobulin Light Chains; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Plasmacytoma; Prednisolone; Vincristine; Waldenstrom Macroglobulinemia

Experimental and clinical evidence indicates that some chemotherapeutic agents may enhance tumor cell immunogenicity. This study was undertaken to test the possibility that melphalan [L-phenylalanine mustard (L-PAM)]--a clinically useful drug--can modulate tumor cells in vivo and in vitro in a syngeneic experimental system of MOPC-315 plasmacytoma in BALB/c mice and that this modulation can be expressed in vivo by enhanced tumor resistance. Tumor-bearing mice were treated with L-PAM intralesionally and ip by a split-course chemotherapy to avoid excessive toxicity of the drug. As a result of this treatment, about 60% of the mice had complete tumor regression; of these, 40-60% were resistant to viable tumor cell challenge and were designated as "cured-immune." Immunogenicity of irradiated MOPC-315 was tested in BALB/c mice; significant protection against tumor cell challenge was not achieved. In vitro L-PAM-treated MOPC-315 cells induced a measurable but weak antitumor response. Combination of both therapeutic approaches, i.e., chemotherapy and active immunization by L-PAM-treated tumor cells, was attempted with the use of various schedules. Immunotherapy given after L-PAM-induced tumor regression significantly enhanced in vivo antitumor response to challenge by 10(4) and 10(5) viable MOPC-315 tumor cells. When immunotherapy was attempted before chemotherapy in the presence of actively growing though still occult tumor, it reduced the chemotherapy cure rate and resulted in a low rate of tumor resistance. Addition of BCG did not remarkably affect the results. The findings point to the importance of timing of active immunization relative to tumor load and chemotherapy. The implication is that chemotherapy-induced regression is mediated by host immune mechanisms in this experimental model.

Topics: Animals; BCG Vaccine; Graft Rejection; Immunization; Immunotherapy; Male; Melphalan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma; Time Factors

The appearance of amyloidosis during the course of multiple myeloma is a well known fact and has an overall incidence of 6 to 15%. However, the total transformation of a plasmocytoma into a voluminous amyloid tumor is a very rare event. A female patient was diagnosed of lambda light chain disease after developing a conspicuous rib plasmocytoma over the same region where a pathological fracture had appeared three years before. She was treated with discontinuous courses of melphalan and methyl-prednisolone, and developed a reversible nephrotic syndrome and a pathological fracture of the right clavicle. At necropsy there was generalized amyloidosis and complete substitution of the rib plasmocytoma by amyloid substance, with another important accumulation of amyloid in the region of the clavicular fracture. The present concepts on amyloidogenesis in multiple myeloma are reviewed, and the peculiarities of the present case together with the possible role of initiating factors and the effects of therapy are discussed. The case herein reported appears to represent a human model of focal amyloidogenesis in myeloma.

Topics: Aged; Amyloidosis; Clavicle; Female; Fractures, Spontaneous; Humans; Melphalan; Methylprednisolone; Nephrotic Syndrome; Plasmacytoma; Ribs

In high concentrations of paraproteins in the plasma in the plasmocytoma a hyperviscosity syndrome appears which is characterized by severe disturbances of circulation in various organs. Apart from the usual intermittent cytostatic therapy with melphalan and prednisone in the phase of the primary treatment the therapy of the hypoviscosity syndrome is of particular importance. In these cases in our clinic the therapeutic plasmapheresis stood the test. It is reported on three patients with plasmocytoma and hyperviscosity syndrome, in whom in 1979 apart from the cytostatic treatment repeatedly plasmapheresis were carried out. Furthermore, references to the practical performance of the plasmapheresis with reinfusion of the autologous erythrocytes are given. On the basis of the impressionable improvement of the hyperviscosity syndrome, the slight cost and expenditure of time as well as of the minimum load of the patients the plasmapheresis is recommended as a firm constituent of the therapy of the plasmocytoma.

Topics: Aged; Blood Viscosity; Creatinine; Humans; Melphalan; Middle Aged; Neoplasm Staging; Plasmacytoma; Plasmapheresis; Prednisone

It is reported on the symptomatology, diagnostics and therapy in a 54-year-old patient with a micromolecular plasmocytoma of kappa-type. Here particularly the impressionable improvement of the clinical picture after an intermitting impact therapy with melphalan (alkeran) - prednisolone in a period of treatment of approximately 2 years is emphasized.

Topics: Bence Jones Protein; Humans; Immunoglobulin kappa-Chains; Lumbar Vertebrae; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Osteolysis; Plasmacytoma; Prednisolone; Radiography

Topics: Adult; Drug Therapy, Combination; Female; Humans; Hyperthermia, Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Myeloproliferative Disorders; Plasmacytoma; Pyrogens; Radiotherapy Dosage; Sarcoma, Ewing

Topics: Aged; Anabolic Agents; Antineoplastic Agents; Calcitonin; Carmustine; Cyclophosphamide; Dihydrotestosterone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisolone; Vincristine

A variant of the MPC 11 cell line, M 311, produces a short immunoglobulin heavy chain. When compared with the parental gamma 2b heavy chain, M 311 was found to have a carboxyl terminal deletion comprising the CH3 domain. The COOH-terminal cyanogen bromide (CNBr) cleavage fragment of M 311 is identical to a corresponding segment ofa parental heavy chain CNBr fragment, with the exception of a substitution of asparagine for lysine at the COOH-terminal residue. This observation enabled prediction of both the parental DNA sequence in this region and the genetic mechanism which generated the variant, a frameshift followed by premature termination. This hypothesis is supported by studies of the DNA sequence of the MPC 11 gamma 2b constant region gene.

Topics: Animals; Cell Line; Chromosome Deletion; Genes; Immunoglobulin G; Immunoglobulin gamma-Chains; Macromolecular Substances; Melphalan; Mice; Mutation; Myeloma Proteins; Neoplasms, Experimental; Peptide Chain Termination, Translational; Plasmacytoma

In non-secernent plasmocytomas there are no characteristic changes of serum protein. Diagnostic difficulties may be overcome by cytomorphological examinations, immunofluorescence and electron microscopy. By referring to 4 own observations the value of the electron microscopic characteristics of plasma cells is demonstrated. Subtile investigations in protein diagnostics are required for avoiding incomplete monoclonal immunoglobulins which may greatly enter the kidneys to be overlooked. Generally the prognosis of non-secernent plasmocytomas is not worse than that of other forms.

Topics: Aged; Bone Marrow; Cyclophosphamide; Female; Humans; Immunoglobulins; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisolone

Topics: Adult; Bence Jones Protein; beta 2-Microglobulin; Bone Neoplasms; Fanconi Syndrome; Female; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Lumbar Vertebrae; Melphalan; Neoplasm Metastasis; Plasmacytoma; Prednisone; Radiotherapy Dosage; Spinal Neoplasms; Vincristine

We report that a chemotherapeutic agent (melphalan) can affect the sensitivity of tumor cells to cytotoxic antibody. Depending on the time interval between drug treatment and subsequent exposure to antibody and complement, the tumor cells can be either more resistant or more susceptible to antibody when compared to control cells. The number of tumor cells surviving the combined treatment was determined by a colony inhibition assay. The two antisera used in this study were directed against either virus-specific or myeloma protein-specific antigens on the surface of S107 murine myeloma cells; identical results were obtained with both sera. Twenty-four hours after exposure to the drug, the number of tumor cells surviving the antibody treatment increased. During this period of increased resistance, the tumor cells were temporarily arrested in the G(2) phase of the cell cycle. After this period of maximal resistance, the effect of cytotoxic antibody on the cells changed such that 4 days after melphalan treatment the cells were significantly more susceptible to the antibody than were the sham-treated control cells. The period of increased susceptibility correlated with an increased density of S107 myeloma protein and viral antigens on the surface of the tumor cells. Eight days after the drug treatment, the susceptibility of the tumor cells and the density of surface antigens both returned to normal levels. This study shows that the correct time interval between exposure to a drug and subsequent treatment with antibody is critical for maximal killing of the tumor cells. The basis for the differential sensitivity of the tumor cells to anti-body may be related to the drug-induced changes in the cell cycle and in antigen expression on the cell surface.

Topics: Antibodies, Viral; Antigens, Surface; Cell Cycle; Cell Line; Cytotoxicity, Immunologic; Leukemia Virus, Murine; Melphalan; Neoplasms, Experimental; Plasmacytoma; Time Factors

Topics: B-Lymphocytes; Biopsy; Child; Clone Cells; Complement C3; Female; Humans; Immunity, Cellular; Immunoglobulin A; Lymph Nodes; Melphalan; Plasmacytoma; Prednisone; T-Lymphocytes

Topics: Bone Neoplasms; Humans; Ischium; Male; Melphalan; Microscopy, Electron; Middle Aged; Plasmacytoma

Topics: Adult; Aged; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisone

Plasmocytoma is generally a systemic disorder and has to be differentiated from solitary plasmocytoma of bones and connective tissue. Diagnosis is based on the typical bone marrow findings, the demonstration of monoclonal paraprotein and the radiological skeletal changes. Prognosis is poor, life expectancy limited to about 18 months. Specific therapy with cytotoxic drugs leads in many cases to marked improvement of the general condition, relative freedom of pain and a decreased complication rate.

Topics: Aged; Aging; Bence Jones Protein; Bone Marrow Cells; Cyclophosphamide; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Osteoporosis; Plasma Cells; Plasmacytoma; Prognosis; Vincristine

A disease in an IgD (lambda) plasmocytoma is described, where after therapy with Alkeran and prednisone a disappearance of all clinical and laboratory findings indicating an activity could be observed. However, there was a progressive development of a picture of encephalomyelitic and polyradicular neuritic syndrome in the female patient with all signs of a recidivous temporary intracranial hypertension which could not be cured. The aetiology of these processes could only be found by the autopsy which revealed an isolated massive infiltration of the meninges and the sheaths of the spinal cord nerves with atypical plasma cells. No signs of the tumour could be identified in other organs. Such localization of the disease, as it is described here, is the first observation of its king. Problems of clinical diagnosis and treatment are discussed.

Topics: Encephalomyelitis; Female; Humans; Hypertension; Immunoglobulin D; Melphalan; Middle Aged; Neurologic Manifestations; Paralysis; Plasmacytoma; Polyradiculopathy; Prednisone

Topics: Bleomycin; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Melphalan; Methotrexate; Osteosarcoma; Plasmacytoma; Prednisone; Sarcoma, Ewing; Vincristine

Topics: Adrenal Cortex Hormones; Adult; Aged; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Remission, Spontaneous; Urethane

A patient with multiple myeloma died of an acute myeloid leukaemia 15 years after onset of the former. At time of diagnosis the 39 year-old-patient had bone marrow infiltration of maximally 32 plasma cells/100 white bone marrow cells, a paraprotein (IgG, light-chain type lambda), osteoporosis of late onset and occasional osteolysis. The long survival time, as well as the acute myeloid leukaemia, are probably due to the effective treatment, first with cyclophosphamide (198 g over four years), later melphalan (3000 mg over eight years).

Topics: Cyclophosphamide; Humans; Immunoglobulin G; Leukemia, Myeloid, Acute; Long-Term Care; Male; Melphalan; Middle Aged; Osteoporosis; Plasmacytoma; Time Factors

Topics: Antineoplastic Agents; Carmustine; Cyclophosphamide; Drug Therapy, Combination; Humans; Melphalan; Multiple Myeloma; Plasmacytoma; Prednisolone; Prognosis; Remission, Spontaneous; Testosterone

Topics: Adult; Aged; Antineoplastic Agents; Chlorambucil; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Melphalan; Middle Aged; Plasmacytoma; Prognosis; Remission, Spontaneous

Topics: Alkylating Agents; Animals; Carcinoma 256, Walker; Cells, Cultured; Chlorambucil; Cyclic AMP; Drug Resistance; Electrophoresis; Female; Kinetics; Lymphoma; Male; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Phosphoric Diester Hydrolases; Plasmacytoma; Rats; Time Factors; Transplantation, Homologous

Topics: Humans; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Male; Melphalan; Methods; Middle Aged; Nandrolone; Plasmacytoma

Two cases of the development of acute myeloid leukemia (AML) after treatment with alkylating agents are reported. In Case 1, melphalan and then cyclophosphamide had been given for multiple myeloma. 46 months after onset of cytostatic treatment AML occurred, as confirmed cytochemically and by qualitative determination of urinary lysozyme. In Case 2, cyclophosphamide had been given for rheumatoid arthritis. After a latency of 34 months 'smouldering leukaemia' developed with an atypical monocytic leukaemic cell population. In a third case, multiple myeloma and monocytic leukaemia developed synchronously. The causative role of melphalan and cyclophosphamide in the development of AML seems securely established. Despite the risk of alkylating agents in the treatment of multiple myeloma or Hodgkin's disease causing AML, they should not be replaced, as other drugs have been shown to be less beneficial. On the other hand, alkylating agents should be used with great caution in the treatment of non-malignant diseases.

Topics: Aged; Alkylating Agents; Arthritis, Rheumatoid; Cyclophosphamide; Female; Humans; Immunoglobulin G; Leukemia, Monocytic, Acute; Male; Melphalan; Middle Aged; Muramidase; Plasmacytoma; Time Factors

The mouse plasma cell tumor Adj PC-5 grows slowly due to a large loss of cells from the growth fraction into nonprolifeative, end-stage cells. All tumor cells with the capacity to form a colony appear to be in cell cycle. Marked tumor specificity of several alkylating agents could not be explaned by differences in the porliferative state of myeloma and normal marrow cells. The sensitivity of different mouse myelomas to an alkylating agent varies considerably. The factors determining whether a mouse myeloma is sensitive to an alkylating agent are probably related to structure of the agent and intrinsic properties of the cell, rather than to the agent's mechanism of action.

Topics: Alkylating Agents; Animals; Bone Marrow; Bone Marrow Cells; Bone Neoplasms; Cell Division; Cells, Cultured; Cyclophosphamide; Cytarabine; Disease Models, Animal; Kinetics; Melphalan; Methotrexate; Mice; Mice, Inbred BALB C; Myeloma Proteins; Neoplasms, Experimental; Plasmacytoma; Thymidine; Tritium; Vinblastine; Vincristine

Clinical and electrophoretic data were evaluated in 334 consecutive patients with myeloma or monoclonal peaks on serum or urine electrophoresis. Of the 242 patients with myeloma, 7% had localized plasmacytomas with absent or low level monoclonal peaks on electrophoresis and received only radiotherapy to focal disease areas. Chemotherapy was also withheld from eight other patients in an indolent clinical phase of multiple myeloma. Disease progression was apparent in about one third of the patients with localized and indolent myeloma within 12 months. Forty-three patients had idiopathic peaks on serum electrophoresis; more than 90% were of the IgG type with levels less than 3.0 gm/100 ml. Serial elecrtophoreses, immunoglobulin quantitations, and skeletal radiographs are recommended for the evaluation of patients with idiopathic peaks, the classification of early phases of myeloma, and the confirmation of tumor mass change.

Topics: Bence Jones Protein; Blood Protein Electrophoresis; Bone Neoplasms; Female; Hemoglobins; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmacytoma; Prognosis

Topics: Adult; Blood Protein Disorders; Dexamethasone; Drug Therapy, Combination; Female; Humans; Melphalan; Plasmacytoma; Remission, Spontaneous

Data are presented on the response rates, maximum rate of cell kill, and survival rates for individual and groups of mice with MOPC 104E myeloma treated with a variety of chemotherapeutic agents and combination regimens used in clinical human myeloma. The tumor immunoglobulin M measurements are used to evalutae the therapeutic effects of drugs. Prednisolone and mescaline, when given as single drugs, showed no therapeutic action and the animals died of tumor as in the controls. The immunoglobulin M values are very similar and ranged between 8,125 and 13,410 mug/mouse. Prednisolone and melphalan given in combination indicated therapeutic effect. 1,3-Bis(2-chloroethyl)-1-nitrosourea-cyclophosphamide-prednisolone combination caused tumor regression but was toxic as shown by the immunoglobulin M values and percentage of survival. The complications and potential uses of this system, which utilized only 40 animals in 64 days, are discussed.

Topics: Animals; Antineoplastic Agents; Carmustine; Cell Line; Cell Survival; Cyclophosphamide; Disease Models, Animal; Drug Therapy, Combination; Female; Immunoglobulin M; Melphalan; Mescaline; Mice; Mice, Inbred BALB C; Multiple Myeloma; Neoplasms, Experimental; Plasmacytoma; Prednisolone; Time Factors

Topics: Cyclophosphamide; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Remission, Spontaneous

Two patients with multiple myeloma and one patient with a plasma-cytoma are reported in whom acute leukaemia developed following long-term treatment with melphalan. Each patient had a complete remission of the plasma cell disorder during which time the bone marrow was moderately to severely hypoplastic. The end of the clinical remission was heralded by a dyserythropoietic anaemia which persisted several months before the emergence of the terminal acute leukaemia. Marked chromosomal abnormalities were observed in marrow cells during the dyserythropoietic phase.

Topics: Bone Marrow; Bone Marrow Cells; Chromosome Aberrations; Chromosomes; Erythropoiesis; Female; Humans; Leukemia; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmacytoma

After mutagenesis of cultured mouse myeloma cells with ICR 191 or Melphalan, variant clones were isolated that synthesized immunoglobulin heavy chains shorter than those produced by the parent. These variants fell into two phenotypes, based on the size, serology, and pattern of assembly of the heavy chain. Variant chains of both types no longer reacted with antisera directed either against the Fc (C-terminal half of the heavy chains) or subclass-specific IgG(2b) determinants. Comparative ion exchange chromatography of tryptic-chymotryptic peptides confirmed that the variant heavy chains differed structurally from those of the parent and from each other. A conversion from one phenotype to the other has been observed.

Topics: Acridines; Animals; Cell Line; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Epitopes; Immunodiffusion; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Immunoglobulin Heavy Chains; Melphalan; Mice; Mutation; Myeloma Proteins; Phenotype; Plasmacytoma; Rabbits

Topics: Adenine Nucleotides; Adenosine Diphosphate; Amidines; Antibiotics, Antineoplastic; Bleomycin; Blood Platelets; Breast Neoplasms; Bronchial Neoplasms; Cyclophosphamide; Doxorubicin; Firefly Luciferin; Fluorouracil; Glyoxal; Hodgkin Disease; Humans; Hydrazones; Leukemia; Luciferases; Lymphocytes; Melphalan; Methotrexate; Neoplasms; Nephelometry and Turbidimetry; Plasmacytoma; Platelet Aggregation; Vinca Alkaloids

Topics: Bence Jones Protein; Bone Marrow Examination; Female; Humans; Immunoelectrophoresis; Melphalan; Multiple Myeloma; Myeloma Proteins; Plasmacytoma; Radiography; Ribs; Skull

Topics: Alopecia; Amyloidosis; Blood Proteins; Drug Therapy, Combination; Eye Manifestations; Humans; Immunoglobulin D; Immunoglobulin Fragments; Keratosis; Male; Melphalan; Middle Aged; Mucinosis, Follicular; Mucous Membrane; Multiple Myeloma; Nails; Plasmacytoma; Prednisolone; Proteinuria; Scalp; Skin; Syndrome; Trichophyton

Topics: Aged; Biopsy; Cyclophosphamide; Diagnosis, Differential; Frontal Bone; Humans; Immunoelectrophoresis; Immunoglobulin G; Iodine Radioisotopes; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Metastasis; Parietal Bone; Plasmacytoma; Prednisone; Skull Neoplasms; Thyroid Neoplasms; Thyroidectomy; Vincristine

Topics: Adult; Bone Neoplasms; Gastroscopy; Humans; Male; Melphalan; Multiple Myeloma; Plasmacytoma; Radiography; Stomach Neoplasms

Topics: Adenocarcinoma; Amides; Androstanols; Animals; Antineoplastic Agents; Cricetinae; Cyclohexanes; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Estradiol; Female; Hydroxyurea; Imidazoles; Mammary Neoplasms, Experimental; Melanoma; Melphalan; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms, Experimental; Osteosarcoma; Plasmacytoma; Progesterone; Rats; Sarcoma, Experimental; Triazenes

Topics: Aged; Autopsy; Biopsy; Bone Marrow Cells; Cyclophosphamide; Female; Heart Neoplasms; Humans; Kidney Neoplasms; Leukemia, Lymphoid; Lymphocytes; Male; Melphalan; Middle Aged; Multiple Myeloma; Nasal Polyps; Nose Neoplasms; Osteitis Deformans; Plasmacytoma; Pleural Effusion; Prednisolone; Radiography

Topics: Cyclophosphamide; Female; Humans; Male; Melphalan; Plasmacytoma; Prednisone; Procarbazine

Topics: Adult; Aged; Blood Transfusion; Cyclophosphamide; Epitopes; Female; Humans; Immunoelectrophoresis; Immunoglobulins; Male; Melphalan; Microscopy, Electron; Middle Aged; Multiple Myeloma; Myeloma Proteins; Plasmacytoma; Prednisone

Topics: Amino Acids; Animals; Carbon Radioisotopes; Clone Cells; Electrophoresis, Polyacrylamide Gel; Epitopes; Immunodiffusion; Immunoglobulins; Melphalan; Mice; Molecular Weight; Mutation; Plasmacytoma; Tritium

Topics: Adult; Antineoplastic Agents; Bence Jones Protein; Hodgkin Disease; Humans; Immunoglobulin D; Male; Melphalan; Plasma Cells; Plasmacytoma; Radiotherapy; Skin Neoplasms; Testicular Neoplasms

Topics: Adult; Aged; Fractures, Bone; Hip; Humans; Lymph Nodes; Male; Maxillary Sinus; Melphalan; Middle Aged; Osteoporosis; Plasmacytoma; Prednisolone; Radiotherapy

Topics: Adrenal Cortex Hormones; Alkylating Agents; Anabolic Agents; Cyclophosphamide; Humans; Melphalan; Plasmacytoma

Topics: Blood Cell Count; Blood Platelets; Drug Combinations; Humans; Leukocyte Count; Leukopenia; Melphalan; Plasmacytoma; Prednisolone; Prednisone; Thrombocytopenia

Topics: Aged; Female; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; Prednisolone

Topics: Animals; Antigen-Antibody Reactions; Cyclophosphamide; gamma-Globulins; Humans; Melphalan; Multiple Myeloma; Plasmacytoma

Topics: Adult; Aged; Female; Humans; Immunodiffusion; Immunoelectrophoresis; Male; Melphalan; Middle Aged; Plasmacytoma

Topics: Adult; Diagnosis, Differential; Female; Humans; Laminectomy; Male; Melphalan; Middle Aged; Plasmacytoma; Prognosis; Spinal Diseases; Spinal Neoplasms

Topics: Adult; Bronchopneumonia; Cytarabine; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Multiple Myeloma; Plasmacytoma; Thioguanine

Topics: Female; Fractures, Spontaneous; Humans; Mandibular Neoplasms; Melphalan; Middle Aged; Plasmacytoma

Topics: Bone Neoplasms; Humans; Lymphatic Metastasis; Male; Melphalan; Middle Aged; Plasmacytoma; Radius

Topics: Bence Jones Protein; Bone Marrow Examination; Hemoglobinometry; Humans; Hypercalcemia; Melphalan; Multiple Myeloma; Neoplasm Proteins; Plasma Cells; Plasmacytoma; Prognosis

Topics: Alkylating Agents; Animals; Benzopyrenes; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Female; Fibrosarcoma; Hematopoietic System; Kidney; Leukemia L1210; Liver; Liver Neoplasms; Male; Melphalan; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Plasmacytoma; Rats; Sarcoma, Experimental; Sarcoma, Yoshida

Topics: Aged; Bone Marrow; Bone Marrow Cells; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Immune Sera; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Macroglobulins; Male; Melphalan; Osteoporosis; Plasma Cells; Plasmacytoma; Radiography

Topics: Anemia, Hemolytic; Blood Protein Disorders; Chlorambucil; Cryoglobulins; Cyclophosphamide; Diagnosis, Differential; Heavy Chain Disease; Humans; Melphalan; Neoplasms; Plasmacytoma; Waldenstrom Macroglobulinemia

Topics: Blood Protein Disorders; Cyclophosphamide; Humans; Melphalan; Plasmacytoma; Statistics as Topic; Waldenstrom Macroglobulinemia

Topics: Aged; Humans; Laryngeal Neoplasms; Male; Melphalan; Plasmacytoma

Topics: Adrenal Cortex Hormones; Adult; Amyloidosis; Autoimmune Diseases; Bence Jones Protein; Cold Temperature; Cryoglobulins; Humans; Hyperlipidemias; Immunoglobulin M; Male; Melphalan; Mucous Membrane; Multiple Myeloma; Mycosis Fungoides; Osteoporosis; Plasma Cells; Plasmacytoma; Purpura, Hyperglobulinemic; Pyoderma; Skin Manifestations; Skin Ulcer; Tongue; Xanthomatosis

Topics: Aniline Compounds; Animals; Antineoplastic Agents; Blood Protein Electrophoresis; Blood Proteins; Chlorambucil; Cyclophosphamide; Erythrocyte Count; Female; Fluorouracil; Hemoglobinometry; Humans; Leukocyte Count; Melphalan; Mercaptopurine; Methods; Methotrexate; Mice; Models, Biological; Mustard Compounds; Neoplasm Transplantation; Neoplasms, Experimental; Peritoneum; Plasma Cells; Plasmacytoma; Time Factors; Transplantation, Homologous; Triethylenemelamine

Topics: Aged; Blood Sedimentation; Chlorambucil; Cyclophosphamide; Female; Humans; Immunoelectrophoresis; Male; Melphalan; Methods; Middle Aged; Plasmacytoma; Waldenstrom Macroglobulinemia

Topics: Aged; Blood Protein Electrophoresis; Bone Marrow; Bone Marrow Cells; Humans; Humerus; Liver; Lymph Nodes; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmacytoma; Radiography, Thoracic; Radius; Skin; Ultracentrifugation

Topics: Anemia; Blood Protein Disorders; Chlorambucil; Humans; Hypercalcemia; Leukopenia; Melphalan; Plasmacytoma; Thrombocytopenia

Topics: Humans; Melphalan; Multiple Myeloma; Plasmacytoma

Topics: Aged; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Plasmacytoma

Topics: Amyloidosis; Animals; Cortisone; Diet; Electrophoresis; gamma-Globulins; Mechlorethamine; Melphalan; Mice; Microscopy, Electron; Multiple Myeloma; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma

Topics: Aged; Anemia, Pernicious; Bence Jones Protein; Diagnosis, Differential; Electrophoresis; Female; gamma-Globulins; Humans; Immunoelectrophoresis; Male; Melphalan; Middle Aged; Multiple Myeloma; Paper; Plasmacytoma; Prednisone; Vitamin B 12

Topics: Adult; Culture Techniques; Humans; Male; Melphalan; Microscopy, Phase-Contrast; Nasopharyngeal Neoplasms; Plasmacytoma

Topics: Blood Protein Disorders; Blood Protein Electrophoresis; Cyclophosphamide; gamma-Globulins; Humans; Immunoelectrophoresis; Lymphatic Diseases; Melphalan; Multiple Myeloma; Plasmacytoma; Skeleton; Waldenstrom Macroglobulinemia

Topics: Aged; Humans; Male; Melphalan; Plasmacytoma; Prednisone

Topics: Humans; Melphalan; Multiple Myeloma; Neoplasms; Plasmacytoma

Topics: Animals; Blood Protein Electrophoresis; Busulfan; Cyclophosphamide; Freund's Adjuvant; gamma-Globulins; Melphalan; Mice; Multiple Myeloma; Neoplasm Proteins; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Plasmacytoma; Proteinuria; Research; Staphylococcal Infections

Topics: Adolescent; Child; Geriatrics; Head and Neck Neoplasms; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mandibular Neoplasms; Maxillary Neoplasms; Melanoma; Melphalan; Multiple Myeloma; Neoplasms; Orbital Neoplasms; Plasmacytoma; Sarcoma; Sarcoma, Kaposi

Topics: Drug Therapy; Humans; Melphalan; Neoplasms, Plasma Cell; Plasmacytoma