melphalan and Bone-Neoplasms

Sarcomas of the hand and wrist are rare malignancies, which should be referred to high-volume comprehensive cancer centres providing multidisciplinary treatment options. The tumour board should propose patient-oriented oncological pathways as well as sophisticated hand and plastic reconstructive procedures. In Addition, isolated limb perfusion with TNF-alpha and melphalan is likely to lead to preoperative tumour shrinkage allowing for R0 resection in sano. Our clinical results in long-term survivors demonstrate reduced amputation rates and salvage of basic hand function when a risk-adapted treatment rationale is applied.

Topics: Adolescent; Adult; Amputation, Surgical; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Cooperative Behavior; Female; Hand; Humans; Interdisciplinary Communication; Limb Salvage; Male; Melphalan; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Plastic Surgery Procedures; Prognosis; Radiotherapy, Adjuvant; Sarcoma; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha; Wrist

Interdigitating dendritic cell sarcoma is a rare neoplasm forming part of the group of malignancies derived from histocytic cell line. This nosological unit can be detected only by special immunohistochemical exams. A young man aged 25 found a tumorous swelling in the proximal part of his left crus. The pathological process affected proximal tibial epiphysis and adjacent soft tissues. The first FDG-PET examination performed in the process of determining the clinical stage of the disease showed a high activity in the site of primary tumour (SUV 7.71) and in the site of regional inguinal node (SUV 4.25). Histological examination of a diagnostic excision specimen of the tumour in the tibia and the extirpated enlarged regional nodes in the left groin led to the diagnosis of interdigitating dendritic cell sarcoma. The diagnosis was confirmed pathologically by another two centres in the Czech Republic and, due to the unusual nature of the diagnosis, also in Regensburg, Germany. Treatment started with chemotherapy, applied to patients with aggressive lymphomas in the framework of clinical studies, i.e. a combination of MegaCHOP. After 4 cycles, however, there was no visible response on the site of primary tumour. MegaCHOP therapy was therefore discontinued after the 4 cycles. Subsequently, we referred the patient for a high-dose chemotherapy with autologous bone marrow transplantation, similarly to aggressive lymphomas. The collection of blood producing stem cells from peripheral blood was successfully performed after ESHAP chemotherapy. A verificatoin FDG-PET examination was performed before high-dose chemotherapy. Increased activity was detected only in left proximal crus, with an SUV of 4.6. One month after ESHAP chemotherapy, BEAM high-dose chemotherapy with autologous transplantation of blood forming tissue was performed. High-dose chemotherapy was followed up by radiotherapy targeted on the primary tumour in the crus (70 Gy). The third verification FDG-PET examination was performed 3 months after radiotherapy. The examination showed a continuing higher activity in the region of the primary tumour (SUV 2.69) and a new centre of activity was detected in the left inguinal nodes region (SUV4.09). The activity corresponded to the presence of viable tumour tissue in the primary nidus and new metastases in inguinal nodes, without proofs of further proliferation at the time. Nodes of the left groin were removed. Histological examination showed affection of the nod

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carmustine; Cytarabine; Dendritic Cell Sarcoma, Interdigitating; Drug Resistance, Neoplasm; Etoposide; Humans; Leg; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; Positron-Emission Tomography; Soft Tissue Neoplasms; Tibia; Tomography, X-Ray Computed

Ewing tumors remain of poor prognosis, with 5-year overall survival of 55% to 65% in localized patients and not exceeding 25% in primarily metastatic disease. Several reports, mainly in children, have reported that some patients with poor-risk Ewing tumors may benefit from high-dose chemotherapy (HDCT) with autologous stem cell rescue. This retrospective study analyzed 46 patients treated in our institution between 1987 and 2000 for localized or primary metastatic Ewing tumors by HDCT followed by stem cell rescue. Median follow up was 7.1 years. Median age was 21 years (range, 15-46 years). Twenty-two percent of patients had metastases at diagnosis. The tumor site was axial in 56% of patients. Median tumor size was 9.5 cm. The treatment regimen consisted of induction chemotherapy, local treatment, maintenance chemotherapy, and consolidation HDCT based on alkylating agents. No toxic death was observed in the intensive therapy phase. Five-year overall survival and progression-free survival were 63 +/- 7.7% and 47 +/- 7.6%, respectively. Pejorative prognostic factors in this population were metastases at diagnosis (5-year overall survival 34% vs.71%, P = 0.017) and poor pathologic response (5-year overall survival 44% vs.77%, P = 0.03). This retrospective study shows a high long-term survival rate with high-dose chemotherapy in adults.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Carmustine; Cisplatin; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Life Tables; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Prognosis; Retrospective Studies; Risk Factors; Sarcoma, Ewing; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. The efficacy of chemotherapy varies according to the histological type of sarcoma. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy. On the other hand, the efficacy of chemotherapy is not statistically demonstrated in non-round cell sarcomas, e. g., malignant fibrous histiocytoma. Nowadays, several kinds of antitumor agents are usually used for adjuvant chemotherapy, and many authors have reported various kinds of regimens and their clinical results. Commonly used drugs include adriamycin, ifosfamide, cisplatin, methotrexate, cyclophosphamide, dacarbazine, vincristine, and actinomycin-D. Recently, high-dose chemotherapy combined with autologous peripheral blood or bone marrow stem cell transplantation has been begun in patients who do not respond to standard chemotherapy, and a better prognosis is expected.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Dactinomycin; Doxorubicin; Drug Administration Schedule; Humans; Ifosfamide; Melphalan; Mesna; Methotrexate; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms; Vincristine

Attempts to improve outcomes of patients with Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) metastatic to bone/bone marrow (BM) have focused on chemotherapy dose intensification strategies. We now present results achieved with that approach, as carried out at Memorial Sloan-Kettering Cancer Center (MSKCC) and as reported in the literature.. Twenty-one unselected MSKCC patients with newly diagnosed ES/PNET metastatic to bone/BM received the "P6" protocol which includes cycles of cyclophosphamide (4.2 g/m(2))/doxorubicin (75 mg/m(2))/vincristine and cycles of ifosfamide (9 g/m(2))/etoposide (500 mg/m(2)). Patients in complete/very good partial remission (CR/VGPR) after P6 received myeloablative therapy with either total-body irradiation (TBI) (hyperfractionated 15 Gy)/melphalan (180 mg/m(2)) or thiotepa (900 mg/m(2))/carboplatin (1,500 mg/m(2)). We reviewed the literature.. Only one MSKCC patient became a long-term event-free survivor; all but one relapse was in a distant site. Initial responses to P6 were CR/VGPR in 19 patients, but eight of them plus two others developed PD while receiving or shortly after completing P6. Eight patients were treated with TBI/melphalan: four relapsed 2 to 7 months after transplantation; two died early of toxicity; one died of pulmonary failure 17 months after transplantation (no evidence of ES/PNET); and one remains in CR at more than 7 years. The three patients treated with thiotepa/carboplatin relapsed 3 to 4 months after transplantation. All reports on large series of unselected patients with ES/PNET metastatic to bone/BM showed similarly unsatisfactory results. Poor outcome was seen with use of active agents for ES/PNET-cyclophosphamide, ifosfamide, doxorubicin, dactinomycin, vincristine, etoposide - at standard dosages for prolonged periods of time and at higher dosages in intensive regimens for short or prolonged periods of time. No improvements in event-free survival rates occurred with successive cooperative group or large single-institutional studies that used increasingly aggressive chemotherapeutic approaches. Inclusion of ifosfamide with or without etoposide made no difference nor did consolidation of remission with myeloablative chemoradiotherapy. Secondary leukemia emerged as a major risk with dose-intensive regimens.. The MSKCC experience and findings reported in the literature suggest that dose-intensive use of the chemotherapy agents with established activity against ES/PNET is reaching its efficacy and toxicity limits. A major impact on prognosis awaits the development of entirely novel therapies.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Bone Neoplasms; Brain Neoplasms; Child; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Male; Melphalan; Neuroectodermal Tumors, Primitive; Sarcoma, Ewing; Thiotepa; Vincristine; Whole-Body Irradiation

Topics: Amputation, Surgical; Antineoplastic Agents, Alkylating; Arm; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Humans; Hyperthermia, Induced; Leg; Melanoma; Melphalan; Sarcoma; Skin Neoplasms; Tumor Necrosis Factor-alpha

Topics: Animals; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Drug Screening Assays, Antitumor; Extremities; Humans; Immunologic Factors; Interferon-gamma; Melanoma; Melphalan; Mice; Mice, Inbred BALB C; Neoplasms; Sarcoma; Sarcoma, Experimental; Skin Neoplasms; Treatment Outcome; Tumor Necrosis Factor-alpha

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

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

Topics: Acute Kidney Injury; Altretamine; Anemia; Bacterial Infections; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Hypercalcemia; Interferons; Kidney Failure, Chronic; Melphalan; Meningeal Neoplasms; Multiple Myeloma; Spinal Cord Compression; Vinblastine; Vincristine; Vindesine

Topics: Bone Neoplasms; Carmustine; Cyclophosphamide; Drug Therapy, Combination; Humans; Melphalan; Multiple Myeloma; Prednisone; Procarbazine; Urethane; Vincristine

Topics: Amino Acid Sequence; Amyloid; Amyloidosis; Antigen-Antibody Complex; Aspartic Acid; Bence Jones Protein; Bone Neoplasms; Cyclophosphamide; Fluorescent Antibody Technique; Humans; Immunoglobulins; Melphalan; Molecular Weight; Multiple Myeloma; Myeloma Proteins; Peptides; Plasma Cells; Polysaccharides; Ultracentrifugation

Internationally, a single standard chemotherapy treatment for Ewing sarcoma is not defined. Because different chemotherapy regimens were standard in Europe and the USA for newly diagnosed Ewing sarcoma, and in the absence of novel agents to investigate, we aimed to compare these two strategies.. EURO EWING 2012 was a European investigator-initiated, open-label, randomised, controlled phase 3 trial done in 10 countries. We included patients aged 2-49 years, with any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or Ewing-like sarcomas. The eligibility criteria originally excluded patients with extrapulmonary metastatic disease, but this was amended in the protocol (version 3.0) in September, 2016. Patients were randomly assigned (1:1) to either the European regimen of vincristine, ifosfamide, doxorubicin, and etoposide induction, and consolidation using vincristine, actinomycin D, with ifosfamide or cyclophosphamide, or busulfan and melphalan (group 1); or the US regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide induction, plus ifosfamide and etoposide, and consolidation using vincristine and cyclophosphamide, or vincristine, actinomycin D, and ifosfamide, with busulfan and melphalan (group 2). All drugs were administered intravenously. The primary outcome measure was event-free survival. We used a Bayesian approach for the design, analysis, and interpretation of the results. Patients who received at least one dose of study treatment were considered in the safety analysis. The trial was registered with EudraCT, 2012-002107-17, and ISRCTN, 54540667.. Between March 21, 2014, and May 1, 2019, 640 patients were entered into EE2012, 320 (50%) randomly allocated to each group. Median follow-up of surviving patients was 47 months (range 0-84). Event-free survival at 3 years was 61% with group 1 and 67% with group 2 (adjusted hazard ratio [HR] 0·71 [95% credible interval 0·55-0·92 in favour of group 1). The probability that the true HR was less than 1·0 was greater than 0·99. Febrile neutropenia as a grade 3-5 treatment toxicity occurred in 234 (74%) patients in group 1 and in 183 (58%) patients in group 2. More patients in group 1 (n=205 [64%]) required at least one platelet transfusion compared with those in group 2 (n=138 [43%]). Conversely, more patients required blood transfusions in group 2 (n=286 [89%]) than in group 1 (n=277 [87%]).. Dose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide is more effective, less toxic, and shorter in duration for all stages of newly diagnosed Ewing sarcoma than vincristine, ifosfamide, doxorubicin, and etoposide induction and should now be the standard of care for Ewing sarcoma.. The European Union's Seventh Framework Programme for Research, Technological Development, and Demonstration; The National Coordinating Centre in France, Centre Léon Bérard; SFCE; Ligue contre le cancer; Cancer Research UK.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Bone Neoplasms; Busulfan; Cyclophosphamide; Dactinomycin; Disease-Free Survival; Doxorubicin; Etoposide; Humans; Ifosfamide; Melphalan; Sarcoma, Ewing; Vincristine

The outcomes of osteosarcoma with poor prognostic factors, such as poor responders, metastatic disease at diagnosis, and relapsed or refractory disease, are poor. We reviewed the clinical records of the patients diagnosed with osteosarcoma at our institute between 2004 and 2018 who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in our institute. Ten patients of osteosarcoma with poor responder, refractory status, and metastatic disease at diagnosis received high-dose chemotherapy followed by ASCT. Four patients underwent high-dose chemotherapy followed by ASCT with the conditioning regimen consisted of thiotepa and melphalan (MEL). Five patients underwent high-dose chemotherapy followed by ASCT with the conditioning regimen consisted of intravenous busulfan (BU) and MEL. One patient underwent tandem high-dose chemotherapy followed by ASCT with BU and MEL followed by carboplatin and etoposide. None of the ten patients died of regimen related toxicities. None of the five patients with poor responders who underwent high-dose chemotherapy followed by ASCT as part of consolidation therapy died of disease after ASCT. High-dose chemotherapy followed by ASCT might be effective for poor responders in osteosarcoma.

Topics: Adolescent; Bone Neoplasms; Busulfan; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Osteosarcoma; Retrospective Studies; Thiotepa; Transplantation Conditioning; Transplantation, Autologous

Up to 66% of patients show local pulmonary disease progression after pulmonary metastasectomy. Regional treatment with isolated lung perfusion (ILuP) may improve local control with minimal systemic adverse effects. The aims of this study were to evaluate local and distant control after ILuP, determine the effect on overall survival compared with historical controls, and confirm the safety and feasibility of ILuP.. A total of 107 patients with resectable pulmonary metastases of colorectal carcinoma, osteosarcoma, and soft-tissue sarcoma were included in a prospective phase II study of pulmonary metastasectomy combined with ILuP with 45 mg melphalan at 37°C. Local and distant control, overall survival, lung function, and 90-day mortality and morbidity were monitored.. We report 0% mortality, low morbidity, and no long-term pulmonary toxicity. For colorectal carcinoma, median time to local pulmonary progression, median time to progression, and median survival time were 31, 14, and 78 months, respectively. Median time to local progression was not reached for sarcoma, whereas median time to progression and median survival time were 13 and 39 months, respectively. The 5-year disease-free rate and pulmonary progression-free rate were 26% and 44% for colorectal carcinoma and 29% and 63% for sarcoma, respectively.. ILuP with melphalan combined with metastasectomy is feasible and safe. Compared with historical controls, favorable results were obtained in this phase II study for local control. Further evaluation of locoregional lung perfusion techniques with other chemotherapeutic drugs is warranted.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Bone Neoplasms; Colorectal Neoplasms; Combined Modality Therapy; Disease Progression; Female; Historically Controlled Study; Humans; Lung Neoplasms; Male; Melphalan; Metastasectomy; Middle Aged; Perfusion; Prospective Studies; Sarcoma; Survival Analysis

Influence of age and sex on chemotherapy-related toxicity was evaluated in children (3-9 years), adolescents (10-17 years), and adults (up to 40 years) with localized Ewing sarcoma (ES) enrolled in the ISG/SSG III protocol. Treatment was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, dactinomycin, and etoposide. High-dose chemotherapy with busulfan and melphalan was given in poor responder patients. The analysis was based on 2191 courses of standard chemotherapy and 230 patients. A lower risk of G4 leukopenia and thrombocytopenia, hospitalization, febrile neutropenia, and red blood cell (RBC) transfusions was observed in males. Use of granulocyte colony-stimulating factor (G-CSF) was more frequent in adults, while children more often received RBC transfusions. A significant correlation between sex and chemotherapy-related toxicity was observed in the study, whereas no significant differences in terms of bone marrow toxicity can be expected according to patient age. Further studies should analyse the role of pharmacokinetics, pharmacogenomics, and clinical characteristics.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hematologic Diseases; Humans; Ifosfamide; Male; Melphalan; Mesna; Neoplasm Staging; Prognosis; Prospective Studies; Sarcoma, Ewing; Sex Factors; Survival Rate; Vincristine; Young Adult

The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control.. From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method.. Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values.. Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms; Combined Modality Therapy; Female; Humans; Lung Neoplasms; Male; Melphalan; Metastasectomy; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Osteosarcoma; Survival Rate; Young Adult

High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival.. Patients aged ≤40 years with nonmetastatic Ewing sarcoma (ES) received vincristine (V), doxorubicin (A), cyclofosfamide (C), actinomycin (Ac), ifosfamide (I) and etoposide (E) (VACAc-IE regimen) as induction chemotherapy. As maintenance treatment, good responders (GR) received nine cycles of VACAc-IE regimen. PRs received three cycles of VAC-IE, mobilizing cycle with CE and HDT with Busulfan and Melphalan with stem cell support.. Three hundred patients [median age 15 years (3-40 years)] entered the study. One patient refused local treatment, 242 (81%) underwent surgery [with radiotherapy (RT) in 80] and 57 (19%) RT alone. No toxic deaths were recorded. Overall GR were 146 (49%). Twenty-eight PR did not receive HDT. At a median follow-up of 64 months (21-116 months), 5-year overall and event-free survival (EFS) were 75% and 69%, respectively. Five-year EFS was 75% for GR, 72% for PR treated with HDT and 33% for PR who did not receive HDT.. High-dose therapy added to the VACA-IE regimen in PR patients is feasible and effective. Selected groups of patients with ES can benefit from HDT.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Kaplan-Meier Estimate; Male; Melphalan; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Sarcoma, Ewing; Vincristine; Young Adult

Isolated limb infusion (ILI) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft-tissue sarcoma of the limb. We report the final results of the first clinical trial of ILI in North America (NCT00004250). Eligible patients had recurrent melanoma or unresectable soft-tissue sarcoma of the limb. Angiographic catheters were positioned just above the knee or elbow of the extremity. General anesthesia was performed, a proximal tourniquet inflated, and a normothermic, low flow, hypoxic infusion of melphalan and dactinomycin circulated through the involved limb for 20 min. Tumor response and morbidity were assessed using standard criteria. Thirty-seven patients were accrued to the trial and 44 ILIs were performed (eight patients had two ILIs); one patient was not treated. Of the 32 evaluable patients, 17 (53%) had a significant response at 3 months: 25% of patients had a complete response and 28% of patients had a partial response. The median duration of complete response was 1 year (5-32 months). Morbidity was acceptable, with peak erythema, edema, and pain experienced at 2 weeks and considered 'moderate' in most patients. No patients developed compartment syndrome or required amputation because of ILI. ILI is well tolerated. More than half of the treated patients experienced a complete or partial response.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, General; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brachial Artery; Catheterization, Peripheral; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Extremities; Female; Humans; Infusions, Intra-Arterial; Male; Melanoma; Melphalan; Middle Aged; Popliteal Artery; Radiography, Interventional; Remission Induction; Sarcoma

Patients with locally advanced or metastatic/recurrent soft tissue and Ewing's sarcoma (EWS) have few treatment options. The purpose of our phase II study was to assess the feasibility, safety and efficacy of tandem high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) in such patients.. Thirteen patients were enrolled onto this study. The first cycle of HDCT consisted of doxorubicin (150 mg/m(2)) and ifosfamide (14 g/m(2)) mixed with mesna (14 g/m(2)), while the second cycle consisted of melphalan (150 mg/m(2)) and cisplatin (200 mg/m(2)).. Eleven out of 13 patients were able to complete both cycles of HDCT. No treatment-related mortality occurred and grade 3 or 4 toxicity was clinically tolerable. The 5-year progression-free survival (PFS) and overall survival (OS) for all patients was 23% (confidence interval, CI: 0-46%) and 31% (CI: 14-70%), respectively. Out of the four patients still alive, two had EWS and measurable disease at the time of ASCT and achieved a complete remission, remaining progression free 126 and 155 months after ASCT.. Our study demonstrates the feasibility and safety of tandem HDCT in patients with high-risk or metastatic/recurrent sarcoma, with some patients achieving long-term PFS and OS.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Disease Progression; Doxorubicin; Feasibility Studies; Female; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Immunoenzyme Techniques; Male; Melphalan; Mesna; Neoplasm Recurrence, Local; Neoplasm Staging; Neuroectodermal Tumors, Primitive, Peripheral; Osteosarcoma; Prognosis; Prospective Studies; Protective Agents; Remission Induction; Rhabdomyosarcoma; Safety; Sarcoma; Sarcoma, Ewing; Survival Rate; Transplantation, Autologous; Treatment Outcome; Young Adult

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

Topics: Adolescent; Adult; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Carboplatin; Central Nervous System Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Etoposide; Feasibility Studies; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Hypocalcemia; Kidney Neoplasms; Melphalan; Neoplasms; Neuroblastoma; Pilot Projects; Recurrence; Risk Factors; Sarcoma; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Wilms Tumor

To improve the prognosis for patients with metastatic Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) using conventional chemotherapy and consolidation high-dose chemotherapy (HDCT) containing busulfan and melphalan.. Ninety-seven unselected patients with newly diagnosed metastatic ES/PNET received induction chemotherapy that included five cycles of cyclophosphamide 150 mg/m2/d for 7 days, doxorubicin 35 mg/m2/d once, followed by two cycles of ifosfamide 1.8 g/m2/d for 5 days, and etoposide 100 mg/m2/d for 5 days. Patients in complete or very good partial remission received HDCT with busulfan total dose 600 mg/m2 and melphalan 140 mg/m2 followed by autologous blood stem cells. Local therapy (surgery and/or radiation therapy) was performed before or after HDCT.. Ninety-seven patients were enrolled from 1991 to 1999 (median age, 12.3 years; range, 0.2 to 25 years). Among them, 75 received HDCT. The 5-year event-free survival (EFS) rate for all 97 patients was 37% and the overall survival (OS) rate was 38%. The EFS after HDCT was 47%. The EFS for the 44 patients with lung-only metastases was 52%, whereas it was 36% for patients with bone metastases without bone marrow involvement. Among the 23 patients with bone marrow metastases, only one survived. The multivariate analysis for both EFS and for OS identified three independent prognostic factors: age, fever at diagnosis, and bone marrow involvement.. Compared with conventional chemotherapy, HDCT may yield benefits for patients with lung-only metastases or bone metastases. These results warrant confirmation in a randomized trial and provide part of the background data for the ongoing Euro-Ewing study.

Topics: Adolescent; Adult; Analysis of Variance; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Child, Preschool; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; France; Humans; Infant; Male; Melphalan; Prognosis; Remission Induction; Risk Factors; Sarcoma, Ewing; Societies, Medical; Survival Analysis

To determine whether consolidation therapy with high-dose melphalan, etoposide, and total-body irradiation (TBI) with autologous stem-cell support would improve the prognosis for patients with newly diagnosed metastatic Ewing's sarcoma (ES).. Thirty-two eligible patients with newly diagnosed ES metastatic to bone and/or bone marrow were enrolled onto this study. Treatment was initially comprised of five cycles of induction chemotherapy (cyclophosphamide, doxorubicin, and vincristine alternating with ifosfamide and etoposide) and local control. Peripheral-blood stem-cell collection was performed after the second cycle of chemotherapy, with delay if the bone marrow was persistently involved. If patients had a good response to initial therapy, they proceeded to consolidation therapy with melphalan, etoposide, TBI, and stem-cell support.. Of the 32 eligible patients, 23 proceeded to high-dose therapy consolidation. Of the nine patients who did not proceed to consolidation, four were secondary to progressive disease and two were secondary to toxicity. Three patients died from toxicity during the high-dose phase of the therapy. The majority of the patients who underwent high-dose consolidation therapy experienced relapse and died with progressive disease. Two-year event-free survival (EFS) for all eligible patients is 20%. The 2-year post-stem-cell reconstitution EFS for the subset of 23 patients who received consolidation therapy is 24%. Analysis of peripheral-blood stem-cell collections by molecular techniques for minimal residual disease showed contamination of at least some samples by tumor cells in all three patients with available data.. Consolidation with high-dose melphalan, etoposide, TBI, and autologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Disease Progression; Dose-Response Relationship, Drug; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Melphalan; Neoplasm Metastasis; Prognosis; Sarcoma, Ewing; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation

We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologous PBPC transplantation in pediatric patients with high-risk solid tumors. From January 1995 to January 1999, 30 patients aged 2-21 years (median 8) were entered into the study. There were 14 females and 16 males. Diagnoses included neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) in 15 patients and rhabdomyosarcoma in five patients. Treatment consisted of busulfan 16 mg/kg, orally over 4 days (from days -5 to -2) in 6 hourly divided doses, and melphalan at a dose of 140 mg/m2 given by intravenous infusion over 5 min on day -1. G-CSF mobilized PBPC were used as autologous stem-cell rescue. One patient developed a single generalized convulsion during busulfan therapy. The most relevant non-hematologic toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and diarrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the other from adult respiratory distress syndrome. Probability of treatment-related mortality was 6.6 +/- 4.5%. With a median follow-up of 18 months (range, 1-48), 19 patients are alive and disease-free, the actuarial EFS at 4 years being 55 +/- 12% for the whole group. We conclude that high-dose busulfan/melphalan for autologous transplantation in children with solid tumors is feasible even in small patients. It is well-tolerated, with an acceptable transplant-related mortality and has proven antitumor activity.

Topics: Adolescent; Adult; Antigens, CD34; Antineoplastic Agents, Alkylating; Blood Cell Count; Bone Diseases; Bone Neoplasms; Busulfan; Child; Child, Preschool; Clonazepam; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Neoplasms; Neuroblastoma; Pilot Projects; Retrospective Studies; Rhabdomyosarcoma; Sarcoma, Ewing; Survival Rate; Transplantation Conditioning; Transplantation, Autologous

Between January 1993 and December 1996, 21 children with advanced solid tumors were entered in a dose-escalating study of high-dose sequential chemotherapy followed by autologous stem cell transplantation. The diagnoses included neuroblastoma (NB) for 13 patients; Ewing's sarcoma (ES) for six patients and osteosarcoma for two patients. Nine patients received therapy as consolidation for primary metastatic disease, and 12 patients had had previous relapses. Treatment consisted of CY given i.v. at a dose of 7 g/m2 on day 1, followed by G-CSF until myeloid recovery. After 3 weeks of rest, all patients were given thiotepa i.v. on days 22-24. The total dose of thiotepa was 450 mg/m2 in three patients, 600 mg/m2 in six patients, and 750 mg/m2 in 12 patients. Melphalan was given i.v. at a dose of 180 mg/m2 i.v. on day 27 followed by stem cell infusion on day 28. Major toxic reactions included stomatitis, esophagitis, diarrhea and dermatitis. Three patients died of treatment-related complications. Twelve patients have had a relapse. Six patients (five with NB and one with ES) are alive in continuous remission 5-50 months (median 36) after transplantation. The results of this study show that it is feasible to administer high-dose sequential chemotherapy to children with advanced solid tumors.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Digestive System Diseases; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Melphalan; Neoplasms; Neuroblastoma; Osteosarcoma; Remission Induction; Salvage Therapy; Sarcoma, Ewing; Survival Analysis; Thiotepa; Treatment Outcome

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Combined Modality Therapy; Etoposide; Graft Survival; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Melphalan; Radiotherapy Dosage; Remission Induction; Sarcoma, Ewing; Survival Rate; Whole-Body Irradiation

A randomized controlled trial was initiated in 1972 to compare two chemotherapeutic regimens [1-3-bis (2-chloroethyl) 1-nitrosourea (BCNU), cyclophosphamide, and prednisone versus melphalan and prednisone], to determine whether the two regimens are cross-resistant, and to evaluate the effectiveness of sodium fluoride, vitamin D, calcium gluconate, and fluoxymesterone in the promotion of bone healing. Initial responses (50%) and survival (36 mo median) for patients treated with the two chemotherapeutic regimens were the same. Patients on either regimen who failed to respond after 6 mo had a very low response rate to the alternative regimen (approximately 10%). Initially responding patients were randomly assigned to either an active drug regimen (sodium fluoride, vitamin D, calcium gluconate, fluoxymesterone) or placebo tablets. There was no significant difference in the low percentage of patients demonstrating bone improvement. Thus, the BCNU, cyclophosphamide, prednisone regimen is as effective as melphalan and prednisone. Fluoride, calcium, vitamin D, and androgenic steroids should not be routinely recommended in myeloma, as they seem to add little to effective chemotherapy and may contribute to morbidity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Calcium Gluconate; Carmustine; Clinical Trials as Topic; Cyclophosphamide; Drug Resistance; Drug Therapy, Combination; Fluoxymesterone; Humans; Long-Term Care; Melphalan; Multiple Myeloma; Prednisone; Radiography; Sodium Fluoride; United States; Vitamin D

A total of 241 patients with early breast cancer had serial bone scans and chest radiographs during the first two years of follow-up after primary treatment. Each patient had had a modified radical mastectomy and been found to have involved axillary nodes. They were part of a prospective randomized trial testing the use of L-phenylalanine mustard L-PAM as adjuvant chemotherapy. During the two years, these patients had a total of 832 serial bone scans and 1091 serial chest radiographs. Twenty-five patients (10.4 per cent) had bone metastases detected on sequential scanning, only 13 of whom, however, were asymptomatic at the time of the positive scan. Twelve (5 per cent) patients were found to have pulmonary metastases on routine sequential chest radiography of whom only 8 were asymptomatic at the time of the positive chest radiograph. It is concluded from this study that, apart from their usefulness in the monitoring of clinical trials, serial bone scans and chest radiographs cannot be recommended routinely in the follow-up of asymptomatic patients because of the low yield and high cost involved.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Follow-Up Studies; Humans; Lung Neoplasms; Melphalan; Middle Aged; Prospective Studies; Radiography; Radionuclide Imaging; Time Factors

A randomized trial of Adriamycin (A) in combination with melphalan (M), (MA therapy), and in combination with M plus cyclophosphamide (C) (MAC therapy), was initiated in 40 evaluable patients with metastatic breast cancer. Twenty-two patients demonstrated an objective response to therapy: 9/20 to the MA regimen, and 13/20 to the MAC regimen. For the 22 responders, median duration of response is not yet achieved for either complete or partial responders, at 10 and 9 months, respectively. The addition of the two alkylating agents to Adriamycin was superior to the single alkylating agent addition, both in total response rate and in completeness of response. Maintenance therapy, after achieving the maximum cumulative dose of Adriamycin, was provided by cyclophosphamide plus methotrexate and 5-fluorouracil (CMF). In 19 patients completing induction and entering maintenance therapy, only one relapse has developed with maximun follow-up at 15 months.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Melphalan; Middle Aged; Neoplasm Metastasis; Remission, Spontaneous; Skin Neoplasms; Time Factors

The authors report the results obtained from the treatment of 13 cases of myeloma by cyclic chemotherapy (melphalan) applied after cellular synchronization with vincristine. The clinical results (maximum 2 years after treatment) were good in 11 cases out of 13. The following laboratory values quickly returned to normal: sedimentation and calcaemia, but there was little change in the immunoglobulins.

Topics: Aged; Anemia; Blood Sedimentation; Bone Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypercalcemia; Male; Melphalan; Middle Aged; Mitosis; Multiple Myeloma; Pain; Periodicity; Vincristine

The effects of various regimens of melphalan combination chemotherapy were evaluated in 508 patients with multiple myeloma. No value was confirmed from the addition of procarbazine or vincristine sulfate to melphalan-prednisone combinations. Ninety-six patients who responded to treatment were allocated at random to one of three maintenance regimens, namely intermittent courses of carmustine with prednisone, continued courses of melphalan with prednisone, or no chemotherapy. There were no differences in the frequency of relapse, the remission duration, or the survival time among these maintenace groups. The frequencies of pneumonia and herpes zoster were higher in patients receiving continued chemotherapy. Continued melphalan-prednisone chemotherapy after the first year is of no major value to responding patients with multiple cyeloma. Attempts to reduce tumor mass maximally with a change in therapy are justified.

Topics: Bone Neoplasms; Carmustine; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Procarbazine; Recurrence; Remission, Spontaneous; Time Factors; Vincristine

A randomized study compared the response of patients with multiple myeloma to chlorambucil, melphalan, and azathioprine. All patients also received a combination of prednisone and fluoxymesterone. Seventy-three of 86 patients entered on the study could have evaluations. The results indicate that melphatan produced more responses than either azathioprine or chlorambucil, but responses to both of these agents were observed. No difference was noted between survival curves for patients with no poor-risk factors as compared to those having at least one poor-risk factor. The only poor-risk factor affecting survival in this group of patients was the blood urea nitrogen level.

Topics: Azathioprine; Blood Urea Nitrogen; Bone Neoplasms; Chlorambucil; Drug Therapy, Combination; Fluoxymesterone; Humans; Melphalan; Multiple Myeloma; Prednisone; Remission, Spontaneous; Risk; Time Factors

A timed sequential chemotherapeutic regimen for multiple myeloma was desinged, based on plasma cell kinetics. A randomized study comparing this regimen with the combination of intermittent melphalan and prednisone was started after an adequate pilot study. Studies with tritiated thymidine labeling and mitotic indexes were performed on patients treated with sequential therapy. Of 13 patients treated with the combination therapy, the responses were as follows: two, objective improvement; nine, subjective improvement; and two, no responses. Of nine patients treated with sequential therapy, the responses in six patients who could have evaluations were as follows: one, objective improvement; two, subjective improvement; one, no response; one, with progressive disease; and one, cardiac death. The two studies showed differences in pertubation of cell kinetics of myeloma that may be related to exponential growth and immunoblobulin types.

Topics: Autoradiography; Bence Jones Protein; Bone Neoplasms; Cell Count; Drug Therapy, Combination; Humans; Immunoglobulins; Kinetics; Melphalan; Methotrexate; Mitosis; Multiple Myeloma; Plasma Cells; Prednisone; Risk; Thymidine; Time Factors; Tritium; Vincristine

Topics: Adult; Aged; Bone Neoplasms; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Remission, Spontaneous; Time Factors

Topics: Adolescent; Adult; Aged; Bone Marrow; Bone Neoplasms; Carcinoma; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Dactinomycin; Drug Synergism; Female; Fluorouracil; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Mitomycins; Parotid Neoplasms; Sarcoma; Urogenital Neoplasms; Vincristine

The study by Whelan and colleagues showed that addition of busulfan and melphalan conditioning and autologous stem cell rescue to conventional EURO-E.W.I.N.G STUDY chemotherapy in local nonmetastatic Ewing sarcoma improves prognosis. However, almost 30% of these study patients will have relapsed before this stage of therapy is reached, and 78% of his patients were at high risk because of inadequate response to the initial chemotherapy given. Further improvement could be achieved by the integration of other novel advances with this approach. Ash and colleagues have shown that the separation of such cases into high- and low-risk groups by using CD56 negativity of the tumor cells is an improvement over current methods with a 100% 10-year progression-free survival in CD56- nonpelvic local isolated Ewing sarcoma patients. Their patients were treated on the SCMCIE 94 protocol, associated with no relapses before 30 months in 24 consecutive patients independent of the CD status. Integration of these novel approaches in diagnosis and treatment would allow truly high-risk patients, who would benefit from the procedure, to reach the busulfan and melphalan stage of therapy and delineate those patients who can be cured without such therapy. Details of the SCMCIE 94 protocol are given and the possible reasons for the different relapse patterns are discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Disease-Free Survival; Humans; Melphalan; Neoplasm Recurrence, Local; Sarcoma, Ewing

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

The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival.. Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m(2) on day -4, cyclophosphamide 2,000 mg/m(2) on days -3, and -2 followed by stem cell infusion.. Fifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths.. Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Femoral Neoplasms; Humans; Male; Melphalan; Methotrexate; Osteosarcoma; Stem Cell Transplantation; Treatment Outcome

Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients.. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT.. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS.. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Female; Humans; Male; Melphalan; Neoplasm Recurrence, Local; Sarcoma, Ewing

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

Drug resistance is a major cause of treatment failure in cancer. Here, we have evaluated the role of STAT3 in environment-mediated drug resistance (EMDR) in human neuroblastoma. We determined that STAT3 was not constitutively active in most neuroblastoma cell lines but was rapidly activated upon treatment with interleukin (IL)-6 alone and in combination with the soluble IL-6 receptor (sIL-6R). Treatment of neuroblastoma cells with IL-6 protected them from drug-induced apoptosis in a STAT3-dependent manner because the protective effect of IL-6 was abrogated in the presence of a STAT3 inhibitor and upon STAT3 knockdown. STAT3 was necessary for the upregulation of several survival factors such as survivin (BIRC5) and Bcl-xL (BCL2L1) when cells were exposed to IL-6. Importantly, IL-6-mediated STAT3 activation was enhanced by sIL-6R produced by human monocytes, pointing to an important function of monocytes in promoting IL-6-mediated EMDR. Our data also point to the presence of reciprocal activation of STAT3 between tumor cells and bone marrow stromal cells including not only monocytes but also regulatory T cells (Treg) and nonmyeloid stromal cells. Thus, the data identify an IL-6/sIL-6R/STAT3 interactive pathway between neuroblastoma cells and their microenvironment that contributes to drug resistance.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cell Survival; Coculture Techniques; Drug Resistance, Neoplasm; Etoposide; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Melphalan; Membrane Potential, Mitochondrial; Mesenchymal Stem Cells; Monocytes; Neuroblastoma; Receptors, Interleukin-6; STAT3 Transcription Factor; Up-Regulation

Cartilage tumours present ongoing therapeutic challenges due to their chondrogenic extracellular matrix that potentially hampers drug delivery, their low percentage of dividing cells, and their poor vascularity. In this context, and based on the affinity of the quaternary ammonium moiety for proteoglycans (PG), we developed a strategy that uses the quaternary ammonium function to selectively deliver DNA alkylating agents to the cartilage tumour tissue. We engineered the quaternary ammonium derivative of melphalan (Mel-AQ) and assessed its antitumoural activity in vitro and in vivo. In vitro, micromolar concentrations of Mel-AQ inhibited the proliferation of human HEMC-SS chondrosarcoma and Saos-2 osteosarcoma cell lines. Moreover, 24-h incubation with 20 μM Mel-AQ induced a 2.5-fold increase in S population and a 1.5-fold increase in subG0G1 population compared to controls. In vivo, Mel-AQ demonstrated antitumour activity in the orthotopic model of primary Swarm rat chondrosarcoma. When given to chondrosarcoma-bearing rats (three doses of 16 μmol/kg at days 8, 12 and 16 post-implant), Mel-AQ demonstrated an optimal antitumour effect at day 43, when tumour cell growth inhibition peaked at 69%. Interestingly, the treatment protocol was proved well tolerated, since the animals showed no weight loss over the course of the study. This antitumoural effect was assessed in vivo by scintigraphic imaging using (99m)Tc-NTP 15-5 developed in our lab as a PG-targeting radiotracer, and tumour tissue was analyzed at study-end by biochemical PG assay with Alcian blue staining. Mel-AQ treatment led to a significant decrease in the PG content of tumoural tissue. These experimental results highlighted the promising antitumour potential of Mel-AQ as a PG-targeting strategy for therapeutic management of chondrosarcoma.

Topics: Animals; Antineoplastic Agents, Alkylating; Bone Neoplasms; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Chondrosarcoma; Drug Screening Assays, Antitumor; Heterocyclic Compounds, 1-Ring; Humans; Male; Melphalan; Proteoglycans; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley

According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on day -2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P = 0.008); OS 0.31 vs 0.71 (P = 0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P = 0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Consolidation Chemotherapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Male; Melphalan; Randomized Controlled Trials as Topic; Retrospective Studies; Sarcoma, Ewing; Young Adult

The Italian Sarcoma Group and the Scandinavian Sarcoma Group designed a joint study to improve the prognosis for patients with Ewing's family tumors and synchronous metastatic disease limited to the lungs, or the pleura, or a single bone.. The study was opened in 1999 and closed to the enrollment in 2008. The program consisted of intensive five-drug combination chemotherapy, surgery and/or radiotherapy as local treatment, and consolidation treatment with high-dose busulfan/melphalan plus autologous stem cell rescue and total-lung irradiation.. During the study period, 102 consecutive patients were enrolled. The median follow-up was 62 months (range 24-124). The 5-year event-free survival probability was 0.43 [standard deviation (SD) = 0.05] and the 5-year overall survival probability was 0.52 (SD = 0.052). Unfavorable prognostic factors emerging on multivariate analysis were a poor histological/radiological response at the site of the primary tumor [relative risk (RR) = 3.4], and incomplete radiological remission of lung metastases after primary chemotherapy (RR = 2.6). One toxic death and one secondary leukemia were recorded.. This intensive approach is feasible and long-term survival is achievable in ∼50% of patients. New treatment approaches are warranted for patients responding poorly to primary chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Melphalan; Myeloablative Agonists; Neoplasm Metastasis; Prognosis; Sarcoma, Ewing; Stem Cell Transplantation; Vincristine; Young Adult

The aim of this retrospective study was to analyze the outcome and identify risk factors associated with progression-free survival (PFS) in 36 children with high-risk neuroblastoma who underwent autologous peripheral blood progenitor cell (PBPC) transplantation between 1994 and 2010. The conditioning regimen used in all cases consisted of high-dose of busulfan and melphalan. Median age at transplantation was 3 years (range: 0.7-14 years). The median times to neutrophil and platelet engraftment were 11 days (range: 9.16 days) and 13 days (range: 9.33), respectively. Twenty-one patients developed nonhematologic toxicity: 15 patients had mucositis, 4 patients developed an engraftment syndrome, and there were 2 cases of liver toxicity. No toxic deaths were observed. There were 15 patients who relapsed. The median time to relapse was 6 months after the transplant (range: 3-13 months). With a median follow-up of 55 months (range: 4-180 months), the PFS was 57% ± 8.5% for the whole group. In multivariate analysis, age below 3 years (P < .005), complete remission (CR) pretransplantation (P < .07) and 1p germline status (P < .01) were variables associated with better outcomes. Patients who were or achieved early CR following transplantation (3 months posttransplantation) had a probability of PFS of 91% ± 6% as compared to patients who did not (PFS 9% ± 8%) (P < .0001). This retrospective study shows that high dose of busulfan and melphalan as conditioning regimen in children with high-risk neuroblastoma is associated with very low morbidity and no mortality in the authors' hands. Younger patients with no 1p deletions and in first CR at transplantation had the better outcome.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Bone Marrow Neoplasms; Bone Neoplasms; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Hematopoietic Stem Cell Mobilization; Humans; Infant; Liver Neoplasms; Male; Melphalan; Neoplasm Staging; Neuroblastoma; Peripheral Blood Stem Cell Transplantation; Remission Induction; Risk Factors; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Hyperthermic isolated limb perfusion with TNF-alpha and melphalan (HILP-TM) achieves high response rates in sarcomas. Melphalan resistance was previously reported to be associated with overexpression of metallothioneins (MTs). Objective of this study was to investigate the influence of MT expression on tumor responses in HILP-TM-treated soft tissue (STSs) and bone sarcomas (BS).. In primary biopsies of 41 HILP-TM-treated sarcomas (37 STSs and 4 BS), MT expression was assessed by an immunoreactive score. The pathologic response to HILP-TM was quantified in the corresponding tumor resection specimens. We studied the association of MT-IRS between histological regression (responder >90%, or non-responder

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Drug Resistance, Neoplasm; Female; Humans; Immunohistochemistry; Male; Melphalan; Metallothionein; Middle Aged; Sarcoma; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Agents, Alkylating; Bone Density Conservation Agents; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Diphosphonates; Humans; Imidazoles; Male; Melanoma; Melphalan; Positron-Emission Tomography; Skin Neoplasms; Tibia; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult; Zoledronic Acid

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Chemotherapy, Adjuvant; Child; Combined Modality Therapy; Cross-Sectional Studies; Dactinomycin; Dose-Response Relationship, Drug; Germany; Humans; Ifosfamide; Intestines; Lung; Melphalan; Multicenter Studies as Topic; Radiation Injuries; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Registries; Retrospective Studies; Risk Factors; Sarcoma, Ewing; Spinal Cord; Survivors; Vincristine

Bone lesions in multiple myeloma (MM) are screened with radiological skeletal survey (RSS) due to its widespread availability. Although bone lesions can be missed by RSS, more sensitive radiological surveys are not as yet recommended for routine use due to the low availability of the methodology and economical considerations.. We report on a 68-year-old male with IgG kappa stage IIIA MM presenting with skeletal pain, fatigue and osteolytic lesions. Since the patient refrained from more intensive therapy, including autologous stem cell transplantation (auto-SCT), he was treated with vertebral irradiation and included in an institutionally guided study which randomized melphalan, prednisone (MP)-lenalidomide (MPR) to MP alone. Although he initially responded, his bone pain reoccurred after three MP cycles. The repeated RSS showed minor, if any changes. Therefore, an MRI was added which revealed extensive osteolyses and extramedullary disease. Justified by these results it was possible to convince the patient that a more intensive therapy approach, including auto-SCT, local irradiation and thalidomide maintenance, was appropriate.. This case calls for an earlier integration of MRI and/or PET/CT scanning in MM, even if RSS remains unchanged, especially if initial bone disease is substantial and/or MM-related symptoms recur. The time course of information and linked decision-making point towards the future significance of an intensified integration of imaging methodologies in the classification and disease management of MM.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Humans; Magnetic Resonance Imaging; Male; Melphalan; Multiple Myeloma; Prednisone; Radiography; Randomized Controlled Trials as Topic

The aim of the study was to determine the activity and toxicity of melphalan as a single agent given in up-front therapy for patients with newly-diagnosed Ewing's family tumours with bone/bone marrow metastases. Nineteen patients were enrolled from 2001 to 2004. The treatment consisted of up-front therapy with melphalan (two courses of 50 mg/m2, 3 weeks apart). The overall rate of response to melphalan (complete response+partial response, according to the RECIST criteria) was 78%. Transient grade 3-4 neutropenia, thrombocytopenia and anaemia were recorded in 97%, 81% and 28% of melphalan courses, respectively. No other relevant toxicities were recorded. Melphalan proved to be active in up-front treatment at non-myeloablative doses, and its toxicity was predictable and manageable. The schedule adopted did not interfere with any further intensive chemotherapy or myeloablative treatment in the majority of cases.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Bone Marrow Neoplasms; Bone Neoplasms; Child; Female; Humans; Male; Melphalan; Pain; Pedigree; Sarcoma, Ewing; Survival Analysis; Treatment Outcome

To evaluate the role of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) as consolidation therapy for children with high-risk Ewing sarcoma (ES) treated at The Hospital for Sick Children (SickKids), Toronto.. The charts of children treated for high-risk ES (defined as metastatic at diagnosis or relapsed) between 1990 and 2005 at SickKids were reviewed. Forty-five children were identified. Twenty patients received ASCT after induction with vincristine, doxorubicin, ifosfamide, cyclophosphamide, and etoposide. Patients with resectable tumor or lung metastases underwent surgery and those with non-resectable tumors were treated with irradiation. Twenty-five patients were treated with conventional chemotherapy (CC). Primary metastatic patients were treated with either a local protocol or as per POG 9354. At relapse, patients were treated with topotecan, cyclophosphamide, then ifosfamide, carboplatin, and etoposide (ICE). Local control was attained with surgery and/or irradiation.. Ten of the 20 patients treated with ASCT are alive (median follow-up 6 years), with 8/10 being in remission more than 5 years from diagnosis. The 3-year overall survival (OS) for ASCT was 59%, (95% CI: 36%, 81%) compared to 34% (14%, 53%) for patients treated with CC (P-value = 0.06). The 3-year event-free survival (EFS) for the ASCT was 39% (17%, 60%) compared to 32% (13%, 50%) in the CC group (P = 0.08).. ASCT appears to add some benefit to conventional multimodality therapy for children with high-risk ES. Randomized controlled trials are warranted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Camptothecin; Carboplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Epirubicin; Etoposide; Follow-Up Studies; Humans; Ifosfamide; Infection Control; Kaplan-Meier Estimate; Melphalan; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation; Postoperative Care; Retrospective Studies; Risk; Salvage Therapy; Sarcoma, Ewing; Topotecan; Transplantation Conditioning; Transplantation, Autologous; Treatment Failure; Vincristine

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Humans; Male; Melphalan; Radiation Injuries; Radiotherapy; Spinal Cord Diseases

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

The outcome for patients with recurrent or progressive Ewing's sarcoma family of tumours (ESFT) is poor. High dose therapy (HDT) has been used for a number of years in an attempt to improve survival; however, evidence for the efficacy of this treatment remains limited.. Between 1992 and 2004, 33 patients with recurrent or progressive ESFT were treated with HDT with bone marrow (n=2), peripheral blood stem cell (n=30), or bone marrow and peripheral blood stem cell support (n=1), at a single institution. HDT was with busulphan and melphalan in 22 patients; melphalan and etoposide in seven patients, three with total body irradiation (TBI); melphalan in three patients (2 with TBI), and busulphan and cyclophosphamide in one patient.. The 2 and 5 year event free survival was 42.5% (95% CI, 26-59%) and 38.2% (95% CI, 21-55%) respectively. There was one treatment related death from colitis, and grade 4 infection was observed in two patients.. Long-term survival can be attained in patients with recurrent or refractory ESFT treated with HDT. However, this treatment is associated with severe toxicity. A need remains for prospective randomised clinical trials of HDT in this group of patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Busulfan; Combined Modality Therapy; Disease Progression; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Neoplasm Recurrence, Local; Sarcoma, Ewing; Treatment Outcome

Two to three percent of the patients with extremity melanoma develop in-transit metastases in the course of their disease. When local treatments fail, isolated limb perfusion (ILP) is a reasonable option, but is generally only applied to patients without evidence of distant metastases. We assessed the value of ILP in stage IV melanoma patients with symptomatic unresectable limb melanoma at our institutions.. A computerized database, containing all patient, tumor, ILP, and follow-up data of 505 ILPs performed in 451 patients between 1978 and 2001, allowed the selection of eight (1.8%) stage IV patients who underwent a palliative ILP for unresectable melanoma lesions on the limbs. All patients had high tumor burden limb disease, according to the combined Fraker and Rossi criteria.. The overall tumor response rate was 88%, with 13% complete and 75% partial response rates. One patient did not respond to ILP. Three partial responding patients attained a complete remission (CR) after excision of the remaining limb lesions. The median duration of hospital stay was 12 days and acute regional toxicity was mild with slight erythema and edema in six and no signs of reaction in two patients. The median limb recurrence-free interval after CR was 6 months and the median duration from the time of distant metastases to death was 15 months. Overall ILP leads to the desired palliative effect in six patients (75%).. ILP should be considered as a palliative treatment in selected stage IV melanoma patients with symptomatic advanced limb disease.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Catheter Ablation; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Extremities; Female; Humans; Length of Stay; Lung Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Staging; Palliative Care; Remission Induction; Skin Neoplasms; Soft Tissue Neoplasms; Tourniquets; Tumor Burden; Tumor Necrosis Factor-alpha

Radiation myelopathy is a rare, devastating, late effect of radiotherapy to the spinal cord. Spinal cord tolerance is currently accepted as about 50 Gy in 1.8-2 Gy fractions. However, the effect of chemotherapy on cord tolerance is unclear. This issue is important, given the increasing use of chemotherapy in combination with radiotherapy. We describe the case of a 17-year-old boy with a right apical paraspinal Ewing's tumour in the neck treated with induction chemotherapy, high-dose chemotherapy (busulfan and melphalan) with peripheral stem-cell rescue and, 4 months later, radiotherapy to the primary tumour site (cervical cord received 50 Gy in 30 fractions). After a latent period of 4 months, he developed a progressive, severe and ultimately fatal radiation myelopathy, which we suggest was due to a synergistic interaction between the high-dose chemotherapy and the radiotherapy. The use of such chemotherapy regimens in Ewing's tumours should be carefully considered, particularly when radiotherapy encompassing the spinal cord is an essential component of management.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Combined Modality Therapy; Fatal Outcome; Humans; Male; Melphalan; Radiotherapy; Sarcoma, Ewing; Spinal Cord; Spinal Cord Diseases

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carmustine; Combined Modality Therapy; Cyclophosphamide; Female; Hodgkin Disease; Humans; Melphalan; Multiple Myeloma; Neoplasms, Second Primary; Prednisone; Procarbazine; Vincristine; Whole-Body Irradiation

Twenty-one children with high-risk Ewing's tumor received high-dose chemotherapy with a PBSCT. Aim of the study was evaluation of efficiency and safety of this procedure. All but three patients have meta-static disease at presentation. There were 11 females and the median age at diagnosis was 12 yr (range 4.5-18 yr). Megachemotherapy consisted of melphalan 140 mg/m2/busulfan 16 mg/kg in 12 patients, melphalan 140 mg2/treosulfan 10.0 g/m2 in two patients and melphalan with other drugs in seven patients. Eight of 11 patients transplanted in CR survived with a median follow-up 24 month (range 14-60) and probability of 2-year OS is 0.68 and DFS is 0.63. There was no severe regimen-related toxicity in this group. Children transplanted without remission died: Two of them due to transplant related causes and eight had progression of disease in a median time 7 month after PBSCT. Megachemotherapy with PBSCT is a safe procedure in children with Ewing's sarcoma in remission. Autologos transplantation in children with metastatic Ewing's sarcoma seems to improve their outcome. Patients with Ewing's sarcoma, resistant to conventional therapy and with recurrent disease did not benefit from megachemotherapy. New approaches such as anti-tumor vaccination or using of imatinib are reasonable to introduce in patients with relapsed or resistant to therapy Ewing's tumor.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Sarcoma, Ewing; Survival Rate; Transplantation, Autologous

In 3 patients over 75 years of age with a malignancy, limb salvage was achieved through the application of isolated limb perfusion with melphalan with or without tumour necrosis factor alpha: an 82-year-old woman with extensive locoregional melanoma metastases on her lower leg, a 78-year-old woman with a large, ulcerating recurrence of melanoma on her lower leg and an 83-year-old woman with recurrent sarcoma of the lower arm. There were no complications and the women recovered well. Isolated limb perfusion can be effectively and safely used in older patients with irresectable tumours of the extremities, offering them limb salvage for the remainder of their lives.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Humans; Limb Salvage; Melanoma; Melphalan; Neoplasm Recurrence, Local; Sarcoma

Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity.. Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation.. The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME.. TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Bone Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Disease-Free Survival; Etoposide; Female; Humans; Male; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Sarcoma, Ewing; Survival Analysis; Whole-Body Irradiation

Eight children developed osteochondroma (OS) at a mean of 88 months after hematopoietic stem cell transplantation (HSCT). The mean age at HSCT was 56 months (12-84). This represents a cumulative incidence of 20% among patients less than 18 years of age transplanted from 1981 to 1997. These eight patients underwent allogeneic (n = 2) or autologous (n = 6) transplantation for either acute leukemia (n = 6) or neuroblastoma (n = 2) after a conditioning regimen including TBI (n = 7) or a combination of Bu and CY. OS was multiple in seven patients and solitary in one. Eight lesions were resected and all were benign. Four children received growth hormone before diagnosis of OS, but there was no clinical, radiological or histological difference between those who did not. Univariate analysis showed an increased rate associated only with autologous HSCT, with a 31.7% probability of a new OS at 12 years after HSCT. Osteochondroma should be added to the other adverse effects of HSCT in children.

Topics: Actuarial Analysis; Acute Disease; Bone Neoplasms; Busulfan; Child; Child, Preschool; Cranial Irradiation; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myeloid; Male; Melphalan; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Neuroblastoma; Osteochondroma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation Conditioning; Whole-Body Irradiation

High-dose chemotherapy with autologous peripheral blood stem cell transplantation was administered to 10 patients with refractory bone and soft tissue sarcoma (2 patients with primitive neuroectodermal tumor, 4 patients with Ewing's sarcoma, 3 patients with synovial sarcoma and one patient with osteosarcoma). Busulfan 4 mg/kg x 4, melphalan 140 mg/m2 and thiotepa 200 mg/m2 x 3 were used in the high-dose chemotherapy. Complications related to the treatment were limited to one patient who developed hepatic veno-occlusive disease, no serious complications were seen in the other patients. Four patients died of their disease, one patient was alive with the disease and 5 patients were alive with no evidence of disease. The prognosis for non-resectable primitive neuroectodermal tumor and Ewing's sarcoma is said to be very poor. However, there are some patients in whom the disease is kept in remission by high-dose chemotherapy with autologous peripheral blood stem cell transplantation, so this therapy may be a possible substitute for radical operation. With spindle cell sarcomas, the efficacy of this treatment was temporary, so it will be necessary to investigate frequent high-dose chemotherapy and to change the high-dose chemotherapy regimen.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Combined Modality Therapy; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Sarcoma; Sarcoma, Ewing; Sarcoma, Synovial; Soft Tissue Neoplasms; Thiotepa; Transplantation, Autologous

Isolated limb perfusion (ILP) with recombinant tumour necrosis factor-alpha (rTNF-alpha) and melphalan has recently been reported to induce major tumour responses and permit limb salvage in over 80% of patients with unresectable soft-tissue sarcomas of the extremities. We investigated whether TNF-based ILP could allow limb-sparing surgery in patients with primary, recurrent or metastatic bone sarcoma to the lower extremity who met the criteria for an amputation and had failed or refused chemotherapy.. From August 1992 to December 1997, we employed ILP with rTNF-alpha and melphalan in 13 patients with unresectable bone sarcoma of the lower extremity, all of whom were candidates for amputation. The aim was to reduce tumour size and allow the performance of a limb-sparing surgery (LSS).. Following ILP, none of the patients had severe local toxicity and only one patient experienced significant systemic side-effects. LSS was subsequently performed in nine of the 13 patients. LSS was feasible in an additional three patients but was not performed because of the emergence of diffused metastatic disease.. ILP with rTNF-alpha and melphalan can allow limb salvage in patients wih locally advanced bone sarcomas who had failed standard treatment options. Its potential role in the treatment of unresectable bone sarcomas of the extremities merits further evaluation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Leg; Male; Melphalan; Middle Aged; Recombinant Proteins; Sarcoma; Treatment Outcome; Tumor Necrosis Factor-alpha

Eighteen patients with poor risk Ewing's sarcoma (including 11 patients with metastatic disease at presentation) received consolidation therapy of busulphan and melphalan with autologous stem cell rescue. There were nine females. The median age at diagnosis was 14.2 years (range 2.75-30 years). There was one early death due to cytomegalovirus pneumonitis. One patient developed a single generalised convulsion during busulphan therapy. Severe renal toxicity was not encountered. One patient developed veno-occlusive disease of the liver (VOD) which eventually resolved. With a median follow up of 2 years, 13 patients survive including six with initial metastatic disease. We conclude that high-dose busulphan/melphalan is well-tolerated and should be evaluated for efficacy in a larger series of patients with high risk Ewing's sarcoma.

Topics: Adolescent; Adult; Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Busulfan; Child; Child, Preschool; Clonazepam; Combined Modality Therapy; Contraindications; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Male; Melphalan; Neoplasm Metastasis; Phenytoin; Remission Induction; Sarcoma, Ewing; Seizures; Survival Analysis; Transplantation Conditioning; Treatment Outcome

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Combined Modality Therapy; Dacarbazine; Dactinomycin; Evaluation Studies as Topic; Extremities; Humans; Hyperthermia, Induced; Incidence; Melanoma; Melphalan; Neoplasm Metastasis; Osteosarcoma; Rhabdomyolysis; Skin Neoplasms; Treatment Outcome

The prognosis of patients with multifocal primary and early or multiple relapsed Ewing's sarcoma is poor with conventional chemoradiotherapy and surgery. We evaluated the efficacy and feasibility of a myeloablative regimen administered as consolidation treatment for these patients.. The ablative regimens consisted of simultaneous radiochemotherapy: 12 Gy hyperfractionated total-body irradiation (TBI; two doses of 1.5 Gy for 4 days) plus fractionated high-dose melphalan (30 to 45 mg/m2 for 4 days) followed by high-dose etoposide (40 to 60 mg/kg) with or without carboplatin (900 to 1,500 mg/m2) (hyper-ME +/- C). These regimens were applied in a dose-escalation study that included 17 patients. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seven patients had multifocal primary Ewing's sarcoma, and 10 had early or multiple relapse. We performed a matched-cohort analysis of the 17 grafted patients with 41 historic controls matched for sex, age, diagnosis, extent of disease, interval from diagnosis to transplant in the transplant group, and interval from diagnosis to relapse in the control group.. The probability of relapse in the study patients is 52% at 6 years after the last event before transplantation. In the control group, the probability of relapse at 6 years was 98%. Eight of 17 treated patients are alive in complete remission at a median observation time of 49 months (range, 19 to 76) from the last event before transplantation. Probability of relapse-free survival in the study patients is 45% +/- 12% at 6 years after the last event before transplant, compared with 2% +/- 2% for the historic control group.. Myeloblative therapy with hyper-ME +/- C radiochemotherapy can improve the prognosis of multifocal primary and early or multiple relapsing Ewing's sarcoma.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carboplatin; Child; Cohort Studies; Combined Modality Therapy; Cytokines; Etoposide; Feasibility Studies; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Prognosis; Recurrence; Remission Induction; Sarcoma, Ewing; Survival Analysis; Whole-Body Irradiation

Topics: Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Drug Monitoring; Drug Therapy, Combination; Female; Hemodynamics; Humans; Interleukins; Melphalan; Middle Aged; Soft Tissue Neoplasms; Tibia; Time Factors; Tumor Necrosis Factor-alpha

Type I collagen is the main collagen type found in mineralised bone. Specific immunoassays for PICP (carboxyterminal propeptide of type I procollagen) and ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) allow simultaneous assessment of the synthesis and degradation of type I collagen in serum samples, respectively. Our aim was to find out whether these metabolites of type I collagen are useful markers for following bone turnover and evaluating treatment response in multiple myeloma, which is a good model disease of excessive osteolysis. Fifteen consecutive patients were studied before and throughout their treatment. Samples for serum PICP and ICTP were collected before starting each treatment course of melphalan and prednisolon. Response to treatment was evaluated by following the changes in M protein and bone roentgenograms. The disease was progressing in four and regressive in 11 patients, but in four of these a recurrence occurred. In nonresponders the ICTP concentration was permanently elevated despite treatment. In responders both increased or normal levels of ICTP were initially observed, but they returned to or remained in the reference interval during treatment. The ICTP concentration increased upon recurring disease. There was a strong correlation between the extent of bone lesions and ICTP. There was no correlation between ICTP and PICP, the latter mainly remaining within the reference range, a finding that suggests no change in bone formation. ICTP was a significant predictor for survival in this patient group (P less than 0.05). We conclude that ICTP is a specific and sensitive marker for bone resorption. Simultaneous use of serum ICTP and PICP offers an additional and easy means to follow bone turnover and evaluate the response to therapy in multiple myeloma.

Topics: Biomarkers, Tumor; Bone Neoplasms; Calcium; Collagen; Female; Follow-Up Studies; Humans; Immunoglobulins; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteoporosis; Peptide Fragments; Peptides; Prednisolone; Procollagen; Prognosis; Recurrence; Regression Analysis; Time Factors

An automated column-switching high-performance liquid chromatographic (HPLC) method with ultraviolet detection is described for a simple and rapid determination of melphalan, an alkylating agent, in human plasma following direct sample injection. The system consists of a pretreatment column and an analytical column connected in series via a switching valve. Plasma samples are loaded onto a pretreatment column with an aqueous mobile phase, with which the sample to be analyzed is retained and the solubilized plasma proteins are flushed to be discarded. The retained compound is eluted from the pretreatment column onto the analytical column by using the chromatographic mobile phase with a higher elution capacity. The column-switching technique can be used to achieve an automated assay. Analytical recovery of the compound was 99.1%, and the coefficients of both intra- and interday variations did not exceed 3.5%. The detection limit was 10 ng/ml for the compound. Recovery of melphalan in plasma was only 2.1% after 4 weeks at 25 degrees C, as compared to 24.5% at 5 degrees C and 100.1% at -20 degrees C.

Topics: Adolescent; Blood Proteins; Bone Marrow Transplantation; Bone Neoplasms; Chromatography, High Pressure Liquid; Female; Humans; Melphalan; Protein Binding; Rhabdomyosarcoma

Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease-free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease-free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion.

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Infusions, Intravenous; Injections, Intra-Arterial; Melphalan; Neoplasm Staging; Osteosarcoma; Prognosis; Radiotherapy; Survival Rate; USSR; Vincristine

Stage I neuroblastoma in a seven-year-girl have had local recurrence with bone metastasis. Second surgery was performed after the aggressive chemotherapy including cisplatin, VP16, cyclophosphamide, vincristine and doxorubicin. She underwent allogeneic bone marrow transplantation from her HLA identical brother, following the preparative regimen consisting of high-dose melphalan and total body irradiation (12 Gy). Clinical course after the transplantation was uneventful. She is still alive with no evidence of disease for twenty-eight months after the transplantation. It is suggested that bone marrow transplantation is an effective way of therapy even in a patient with relapsed neuroblastoma.

Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Child; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Melphalan; Neuroblastoma; Remission Induction; Whole-Body Irradiation

Circulating hematopoietic stem cells were collected by three consecutive leukaphereses during post-chemotherapy expansion of the stem cell pool in a 3-year-old boy with advanced and therapy-resistant neuroblastoma. The cells were fractionated by discontinuous Percoll gradient centrifugation, frozen in a programmed freezer and then stored in liquid nitrogen. Following high-dose chemotherapy, the cells were thawed rapidly and re-infused into the patient. Early evidence of marrow recovery was first noted at day 13 and the times required to achieve a granulocyte count of greater than 0.5 x 10(9)/L and a platelet count of greater than 50 x 10(9)/L were 21 days and 30 days, respectively. This new marrow-rescue operation may have potential in cancer therapy as an alternative to bone marrow transplantation and further clinical investigation is warranted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Preservation; Bone Neoplasms; Child, Preschool; Cisplatin; Freezing; Hematopoietic Stem Cell Transplantation; Humans; Leukapheresis; Male; Melphalan; Neuroblastoma; Podophyllotoxin; Transplantation, Autologous

Topics: Adolescent; Bone Neoplasms; Child; Female; Humans; Melphalan; Ovarian Diseases; Sarcoma, Ewing

Four patients with osteosarcoma were treated with intensive chemotherapy and autologous bone marrow transplantation (ABMT). The patients received high-dose methotrexate (9-12 mg/m2) with citrovorum factor rescue, high-dose melphalan (60 mg/m2 X 3), actinomycin D (0.5 mg/m2 X 3), adriamycin (30 mg/m2 X 2) and high-dose cyclophosphamide (60 mg/kg X 2) during 4 weeks. Bone marrow was aspirated and cryopreserved before treatment and reinfused 48 hours after the completion of chemotherapy. Two of four patients had advanced osteosarcoma with multiple pulmonary metastasis, one of whom had responded well and achieved partial response while the other had shown no response, and both patients died of disease progression 4 and 11 months after ABMT, respectively. The other two patients who received this regimen at an earlier disease stage for prevention of pulmonary metastasis, are alive and well without any evidence of metastasis 31 and 18 months after ABMT, respectively. This regimen was tolerated well in all patients except for mild nausea and vomiting. No infectious episodes were observed during the period of aplasia which continued for 19 to 38 days after marrow infusion. These results suggest that this supralethal combination chemotherapy is safe and tolerable when used with ABMT and effective for patients with osteosarcoma, especially when applied in the non-metastatic phase.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Bone Neoplasms; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Humans; Male; Melphalan; Methotrexate; Osteosarcoma; Transplantation, Autologous

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

The case of a 4 year 8 months old boy with neuroblastoma of unknown primary, metastatic to the bone and to the bone marrow is presented. After achieving a partial remission with six cycles of conventional chemotherapy, the patient was given supraconventional chemotherapy (melphalan 220 mg/m2 bolus i.v.) in an effort to eliminate residual disease. Prior to the administration of the drug, 560 cc of autologous bone marrow, morphologically free of tumor was harvested (total 110 X 10(8) nucleated cells) and concentrated to a mononuclear cell fraction with a total of 10 X 10(8) cells. After in vitro purging with the stable metabolite of 4-hydroperoxycyclophosphamide ASTA Z 7654 (40 micrograms/2 X 10(7) mononuclear cells/ml), the mononuclear cell suspension was retransfused 10 hours following the application of high dose melphalan. Hemopoietic reconstitution was delayed with a platelet count reaching 70,000/microliter only after seven months. At the time of this writing (20 months after diagnosis and 16 months after autologous bone marrow transplantation) there is no evidence for active disease according to the bone scan and multiple bone marrow biopsies. In view of the dismal prognosis of patients with neuroblastoma, stage IV it is recommended that further patients should be treated with a slightly modified protocol of the cooperative austrian neuroblastoma study.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Bone Neoplasms; Child, Preschool; Cyclophosphamide; Humans; Male; Melphalan; Neoplasm Staging; Neoplasms, Unknown Primary; Neuroblastoma

Two women are described in whom, on the basis of prior therapy for breast cancer and the presence of painful, lytic bone lesions, an initial diagnosis of metastatic breast cancer was made. Further evaluation established the diagnosis of multiple myeloma in both patients. Neither had evidence of recurrent breast cancer. These cases indicate that women with a history of breast cancer in whom lytic bone lesions develop without evidence of extraskeletal metastases should have the diagnosis of multiple myeloma excluded.

Topics: Agammaglobulinemia; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Melphalan; Middle Aged; Multiple Myeloma; Neoplasms, Multiple Primary; Prednisone; Radiography

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

Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.

Topics: Abdominal Neoplasms; Adolescent; Adult; Bone Marrow Transplantation; Bone Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Gastrointestinal Diseases; Humans; Melphalan; Neoplasm Recurrence, Local; Neuroblastoma; Pancytopenia; Sarcoma, Ewing; Transplantation, Autologous

Carminomycin, a new antibiotic made in the USSR, was used in the treatment of 21 patients aged 5 to 15 years with extended osteogenic sarcoma. As a result of the treatment the number of the patients with lifetime prolonged for 1-2 years increased from 7.6 to 46 per cent. It was shown that the drug might be used for the prophylaxis of the localized forms of the disease in children.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carubicin; Child; Child, Preschool; Combined Modality Therapy; Daunorubicin; Drug Evaluation; Follow-Up Studies; Humans; Lung Neoplasms; Lymphatic Metastasis; Melphalan; Osteosarcoma; Time Factors; Vincristine

Sixteen cases of osteosclerotic myeloma and peripheral neuropathy (SM-PN) were reviewed. The neuropathy resembled chronic inflammatory-demyelinating polyneuropathy with predominantly motor disability, high CSF protein levels, and low motor nerve conduction velocities. Twelve of the 16 patients had detectable levels of monoclonal serum proteins, all with lambda light chains, but results of other laboratory studies were usually normal. Most of the patients also had organomegaly, endocrine abnormalities, or both. Treatment of solitary lesions with tumoricidal irradiation usually improved the neuropathy and reversed the nonneurologic abnormalities; chemotherapy for multiple osteosclerotic lesions was less helpful.

Topics: Adult; Aged; Antibodies, Monoclonal; Bone Neoplasms; Female; Humans; Immunoglobulin kappa-Chains; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteosclerosis; Peripheral Nervous System Diseases; Prednisone

Topics: Adolescent; Bone Marrow Transplantation; Bone Neoplasms; Humans; Lung Neoplasms; Male; Melphalan; Sarcoma, Ewing

Topics: Adolescent; Bone Neoplasms; Child; Female; Humans; Lung; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Melphalan; Sarcoma, Ewing; Time Factors; Whole-Body Irradiation

Topics: Bone Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Melphalan; Methotrexate; Osteosarcoma; Vincristine

Topics: Adolescent; Bone Marrow Transplantation; Bone Neoplasms; Humans; Humerus; Male; Melphalan; Neoplasms, Multiple Primary; Osteosarcoma; Transplantation, Autologous

A patient with multiple myeloma who subsequently developed chronic lymphocytic leukemia is reported. Initial studies demonstrated clinical and hematological features of multiple myeloma with an IgM lambda paraprotein. Skeletal disease was a significant presenting feature, although relapse occurred in extraosseous sites, particularly the pleura. He developed chronic lymphatic leukemia 31 months later and immunological studies showed the malignant lymphocytes to have kappa (Kappa) light chain surface immunoglobulin, demonstrating separate clonal origin of this patient's two B-cell malignancies.

Topics: Aged; Bone Marrow; Bone Neoplasms; Humans; Immunoglobulins; Leukemia, Lymphoid; Lymphocytes; Male; Melphalan; Multiple Myeloma; Ribs

Topics: Adolescent; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Evaluation Studies as Topic; Humans; Melphalan; Radiotherapy Dosage; Sarcoma, Ewing; Time Factors; Vincristine

From December 1978 to February 1981 91 regional hyperthermic perfusions with melphalan (1.0 or 1.5 mg/kg body weight) were performed in 87 patients with malignant melanoma of the extremities. During a one-hour perfusion with whole blood at an intramuscular temperature of 42 degrees C the flow rate was 264 +/- 62 ml/min in the upper and 495 +/- 42 ml/min in the lower limb. Apart from one intima dissection there were no serious intraoperative complications. Postoperatively one female patient died on the 19th day from acute right heart failure with severe bone marrow suppression. In six patients intransigent metastases appeared after an average of six months. One patient developed lung metastases 7 months postoperatively from which he died. Seventy-nine patients remained free of tumour during the observation period.

Topics: Adult; Aged; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Hot Temperature; Humans; Intraoperative Complications; Male; Melanoma; Melphalan; Middle Aged; Postoperative Complications; Skin Neoplasms

Topics: Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Osteosarcoma; Radiotherapy Dosage

In order to study the response of patients with multiple myeloma of the bones (MM) to various anti-cancer drugs (Melphalan M, Cyclophosphamide Cy, Nitrosourea NU, Vincristine V, Adriamycine A and Prednisone P), 70 MM received the following treatment : 1) Induction therapy : a) M and P or b) M and Cy and P ; 2) Levelling with partial or complete response : V Cy P (in case a) or V M Cy P (in case b) ; 3) Relapse : A and NU. The following results were obtained : 1) Only 42.6% of patients respond to induction therapy ; 2) Fewer than 10% of patients showing a response reach a second levelling with Vincristine ; 3) 50% of those not showing a response reach a levelling between --20 and --50 and have prolonged survival ; 4) Only 20% of non responders are improved by Cy P or A and NU. The median actuarial survival is 42 months. Among the responders two poor prognosis factors must be underlined : hypercalcemia and the speed of response.

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Carmustine; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Vincristine

Topics: Bone Neoplasms; Breast Neoplasms; Cyclophosphamide; Humans; Lymphoma; Melphalan; Multiple Myeloma; Neoplasm Metastasis; Palliative Care; Prednisone; Vincristine

7 patients with advanced malignant melanoma who were given cyclophosphamide (500 mg intravenously) 7 days before a high dose of melphalan (140 mg/m2) had a more rapid recovery of the peripheral white-cell count than did 4 patients who received melphalan alone. "Priming" by cyclophosphamide might be a practicable means of offsetting the bone-marrow toxicity of some chemotherapy regimens and it may permit higher doses of drugs to be given safely.

Topics: Blood-Brain Barrier; Bone Marrow; Bone Neoplasms; Cyclophosphamide; Drug Evaluation; Drug Therapy, Combination; Humans; Injections, Intravenous; Leukocyte Count; Leukocytes; Melanoma; Melphalan; Neoplasm Metastasis; Premedication; Skin Neoplasms

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

Results of surgery and chemotherapy in osteosarcoma are based on a retrospective investigation of 122 patients from 1930 till 1978 treated at the Orthopaedic Department of Vienna University and documented at the Viennese Bone Tumour Registry. Adequate surgery is considered to be the radical elimination of the tumour in an oncological sense, e.g. amputation or resection. Our own patients were examined in this light and different forms of chemotherapy are compared and their efficacy as adjuvant treatment is evaluated. The turning point in the prognosis of osteosarcoma came with the introduction of high-dose methotrexate therapy (HDMTX) in 1972 and which has been employed at the Orthopaedic Department of Vienna University since 1975. So far, HDMTX has been used in the management of 18 patients and the short-term results confirm the excellent results reported in the literature. The consequent change in policy with regard to the current surgical approach to osteosarcoma is discussed in detail.

Topics: Adolescent; Amputation, Surgical; Bone Neoplasms; Child; Cyclophosphamide; Female; Femur; Humans; Humerus; Male; Melphalan; Methotrexate; Mitomycins; Osteosarcoma; Prognosis; Prostheses and Implants; Tibia

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

Since 1968 we have been treating a patient, who has had a combination of pyoderma gangraenosum (dermatitis ulcerosa) and signs that may indicate early multiple myeloma. She also had carcinoma of the colon, which was successfully operated. The pyoderma healed later after intensive and successful cytostatic treatment of the "myeloma". The ulcers remain practically healed and the protein pattern is normal in May 1977. Such cases are rare and a search in the literature has not been very rewarding. In our own series of more than 200 cases with myeloma this combination is unique. The lieterature is discussed in detail with data on the follow-up on some of the patients.

Topics: Aged; Bone Neoplasms; Drug Evaluation; Female; Follow-Up Studies; Humans; Immunoglobulin A; Male; Melphalan; Middle Aged; Multiple Myeloma; Pyoderma; Skin Ulcer

Topics: Aged; Bone Neoplasms; Female; Humans; Melphalan; Multiple Myeloma; Ophthalmoplegia; Prednisone

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

Treatment for primary malignant tumors of bone, in the past several decades, has yielded uniformly poor results. Recent progress in chemotherapy and immunotherapy are detailed. An important advance in treating osteogenic sarcoma has been the application of adjuvant chemotherapy after initial amputation. CONPADRI-I and COMPADRI-II chemotherapy (a multiple drug approach) is discussed. Adriamycin in combination or alone has proved effective in treating osteogenic sarcoma. Ewing's tumor is showing increased survival rates from radiation therapy alone, as well as by use of systemic adjuvant chemotherapy combined with local radiation. Adjuvant triple chemotherapy with radiotherapy has resulted in pronounced improvement in survival. Chondrosarcomas are largely chemotherapy-resistant. Immunotherapy in bone tumors still is in the experimental stage and investigations with immunotherapy are preliminary. It appears, however, that the immunological status of a patient definitely relates to prognosis. Through increased sophistication in specific chemotherapy and magnitude of treatment, further advances in treatment of primary malignant bone tumors may be expected.

Topics: Amputation, Surgical; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Immunity, Active; Immunity, Maternally-Acquired; Immunotherapy; Melphalan; Neoplasm Metastasis; Osteosarcoma; Postoperative Care; Sarcoma, Ewing; Vincristine

Topics: Bone Neoplasms; Cyclophosphamide; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Multiple Myeloma; Time Factors

Topics: Adolescent; Bone Neoplasms; Child; Child, Preschool; Chondrosarcoma; Cyclophosphamide; Humans; Infant; Lymphoma, Large B-Cell, Diffuse; Melphalan; Methotrexate; Sarcoma, Ewing

Topics: Bone Neoplasms; Cell Division; Cell Survival; Cyclophosphamide; Drug Administration Schedule; Humans; Immunoglobulin G; Melphalan; Models, Biological; Multiple Myeloma; Prednisone

Topics: Antineoplastic Agents; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Humans; Melphalan; Sarcoma; Vincristine

We reviewed the efficacy of three agents advocated as ancillary therapy in myeloma patients. Intramuscularly administered immune serum globulin (gamma globulin) was ineffective in preventing infection. Hemoglobin level was improved in some myeloma patients receiving androgens. However, the response rate and the degree of leukopenia or thrombocytopenia were not superior with androgen-melphalan-prenisone combination therapy, as compared with those resulting from the two-drug combination without androgen. A controlled study evaluating androgen plus melphalan has not been done. The long-term administration of fluoride, supplemented by calcium and androgen, induced radiologically apparent bone fluorosis, but strengthening of lytic bone was not observed. Neither objective nor subjective benefit was demonstrated in a controlled study comparing the effects of fluoride (without calcium supplement) with those of the placebo.

Topics: Androgens; Bone Neoplasms; Drug Therapy, Combination; Evaluation Studies as Topic; Fluorides; Fluoxymesterone; gamma-Globulins; Humans; Immunotherapy; Melphalan; Multiple Myeloma; Prednisone; Testosterone

Management of some diverse complications of plasma cell myeloma is reviewed with respect to prevention when possible and prompt treatment when necessary. A series of 102 patients from the Duke University Medical Center was surveyed to ascertain the approximate frequency with which renal failure, hypercalcemia, infection, hyperviscosity syndrome, and neurologic disorders occur. Selected patient studies and additional data from the literature emphasize aspects of these complications amenable to therapy aside from that directed at plasma cell growth.

Topics: Acute Kidney Injury; Bacterial Infections; Blood Urea Nitrogen; Blood Viscosity; Bone Neoplasms; Cephalothin; Cyclophosphamide; Cytarabine; Female; Fluoxymesterone; Furosemide; Gentamicins; Humans; Hypercalcemia; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Neurologic Manifestations; Plicamycin; Renal Dialysis

Topics: Adult; Bone Neoplasms; Exophthalmos; Female; Humans; Melphalan; Multiple Myeloma; Orbital Neoplasms; Sphenoid Bone

Topics: Adolescent; Adult; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Bone Neoplasms; Child; Child, Preschool; Evaluation Studies as Topic; Female; Hematopoiesis; Humans; Male; Melphalan; Transplantation, Autologous; Transplantation, Homologous

Because cross-resistance between alkylating agents has not been observed, we attempt in a prospective trial to determine the advantages, if any, in administering three alkylating agents sequentially, alternately, or concurrently. A patient with myeloma, showing progressive shortening of M-protein doubling time from 98 to 15 days, developed an acute terminal phase, characterized by fever and pancytopenia. A similar acute terminal phase was observed in 17 of 50 deaths from myeloma. Since alkylating agents are only effective in controlling the chronic phase of myeloma, future improvements will require the discovery of agents that delay, prevent, or are effective in the treatment of the acute phase. Forty-five patients with kappa- and 36 with lambda-light-chain disease showed no differences in frequency of amyloidosis, renal failure, response to treatment, or survival after treatment with alkylating agents.

Topics: Acute Disease; Alkylating Agents; Bence Jones Protein; Bone Neoplasms; Carmustine; Cell Count; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Mechlorethamine; Melphalan; Multiple Myeloma; Myeloma Proteins; Prednisone; Remission, Spontaneous; Time Factors

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Femoral Neoplasms; Follow-Up Studies; Frontal Bone; Humans; Humerus; Ilium; Male; Mandibular Neoplasms; Maxillary Neoplasms; Melphalan; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Radiotherapy, High-Energy; Sacrum; Sphenoid Bone; Tibia; Vincristine

Rapidly fatal acute myelomonocytic leukemia developed in five patients with multiple myeloma who were treated with melphalan for 28 to 54 months. In each patient, multiple myeloma responded to therapy and progress was satisfactory until the development of acute leukemia. At postmortem examination, leukemic infiltration of organs was seen, and there was little or no evidence of myeloma. Consideration of these cases and a review of the literature suggest that these circumstances represent the development of acute myelomonocytic leukemia rather than plasma cell leukemia; there also appears to be an increased incidence of acute leukemia in multiple myeloma, probably related to the alkylating agent.

Topics: Acute Disease; Aged; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Bone Neoplasms; Hemoglobins; Humans; Leukemia, Myeloid; Leukemia, Plasma Cell; Leukocyte Count; Male; Melphalan; Microscopy, Electron; Middle Aged; Multiple Myeloma; Plasma Cells; Prednisone; Testosterone; Time Factors

Recent advances in the use of chemotherapy for treatment of osteosarcoma have altered out pessimism in this disease. Results are presented from 3 groups of investigators using different agents as adjuvant chemotherapy following immediately upon amputation of the primary. The Roswell Park Memorial Institute began a regime, immediately after amputation, of adriamycin 30 mg/M2 for 3 doses and given every 4-6 weeks. This study was subsequently expanded in a cooperative group (ALGB) and the results on 20 patients analyzed. At 19 months approximately 75 per cent are free of any pulmonary metastases compared with 10-25 per cent expected from amputation alone. Similar results have been obtained by other Centers using different chemotherapeutic agents. In Boston Children's Hospital high dose Methotrexate with citrovorum factor is used. In 12 of these patients local control of the primary by surgery was obtained and of these only 1 developed pulmonary metastases during an observation time of 23 months. At the M. D. Anderson Hospital multi-drug combinations were used including Cyclophosphamide, Vincristine, L-Phenylalamine Mustard and Adriamycin. They reported a survival rate of 55 per cent (10 out of 18). All of these neoplastic agents have toxic side effects but when carefully used these effects are minimized and the quality of life is quite good. Many questions must be answered by future controlled long term follow-up studies.

Topics: Amputation, Surgical; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Lung Neoplasms; Melphalan; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Vincristine

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

There is evidence for the value of the following tests in the diagnosis, monitoring, and prognosis of myelomatosis: (1) serum paraprotein measurements, (2) urine paraprotein (including Bence Jones) measurements, (3) serum ablumin, (4) serum urea, (5) proteins in the urine other than those in 2, and (6) hemoglobin level. During treatment, increased rate of rise in 1 or 2, disproportionate increase in 2, emergence of related paraprotein, loss of 1 or 2 with reticulosarcomatous change, and monocytic leukemia suggest that more malignant subclones can emerge from the original myeloma clone, possibly due to drugs acting on DNA.

Topics: Bence Jones Protein; Bone Neoplasms; Clone Cells; Hemoglobins; Humans; Immunoglobulin A; Immunoglobulin G; Melphalan; Monitoring, Physiologic; Multiple Myeloma; Myeloma Proteins; Prognosis; Serum Albumin; Urea

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: Aged; Amyloidosis; Biopsy; Bone Neoplasms; Cell Nucleus; Cyclophosphamide; Electromyography; Female; Humans; Hypesthesia; Melphalan; Microscopy, Electron; Multiple Myeloma; Muscles; Muscular Atrophy; Musculocutaneous Nerve; Myelin Sheath; Neural Conduction; Reflex, Abnormal

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

Topics: Bone Neoplasms; Cyclophosphamide; Giant Cell Tumors; Humans; Liver; Melphalan; Osteoma, Osteoid; Osteosarcoma; Radiation Effects; Radiotherapy; Radiotherapy Dosage; Sarcoma; Sarcoma, Ewing

Topics: Aged; Amputation, Surgical; Arm; Bone Neoplasms; Cartilage; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Female; Fibrosarcoma; Hemangiosarcoma; Humans; Leg; Liposarcoma; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Sarcoma

Topics: Bence Jones Protein; Bone Neoplasms; Electrophoresis; Female; Fluorescent Antibody Technique; Humans; Immunoelectrophoresis; Immunoglobulins; Male; Melphalan; Middle Aged; Multiple Myeloma; Remission, Spontaneous

Topics: Adolescent; Adult; Amputation, Surgical; Bone Neoplasms; Child; Chondrosarcoma; Female; Humans; Hypothermia, Induced; Hypoxia; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Methods; Osteosarcoma; Radiation Injuries; Tourniquets

Topics: Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Dose-Response Relationship, Radiation; Female; Humans; Lung Neoplasms; Male; Melphalan; Neoplasm Metastasis; Prognosis; Radiotherapy Dosage; Sarcoma, Ewing; Time Factors; Vinblastine

Topics: Antineoplastic Agents; Bone Neoplasms; Chlorambucil; Humans; Melphalan; Multiple Myeloma

Topics: Albuminuria; Bence Jones Protein; Bone Neoplasms; Cyclophosphamide; Female; Fractures, Spontaneous; Glucocorticoids; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Pain; Prognosis

Topics: Adrenal Cortex Hormones; Albuminuria; Bence Jones Protein; Bone Neoplasms; Cyclophosphamide; Fractures, Spontaneous; Humans; Melphalan; Multiple Myeloma; Pain

Topics: Adolescent; Aged; Bone Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Neoplasms; Ovarian Neoplasms; Sarcoma, Ewing; Testicular Neoplasms; Thrombocytopenia; Tonsillar Neoplasms; Uterine Neoplasms

Topics: Adolescent; Amputation, Surgical; Anti-Bacterial Agents; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Child; Chondrosarcoma; Giant Cell Tumors; Hip; Humans; Lymphoma, Large B-Cell, Diffuse; Melphalan; Neoplasm Metastasis; Osteosarcoma; Radioisotopes; Sarcoma, Ewing; Shoulder; Vitamins

Topics: Animals; Bone Neoplasms; Dog Diseases; Dogs; Melphalan; Sarcoma

Topics: Bence Jones Protein; Bone Neoplasms; Cyclophosphamide; Follow-Up Studies; Humans; Melphalan; Multiple Myeloma

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Child; Extremities; Female; Hemorrhage; Humans; Hypotension; Leukopenia; Lymph Node Excision; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Methods; Middle Aged; Postoperative Complications; Sarcoma; Skin Neoplasms

Topics: Adult; Aged; Blood Protein Electrophoresis; Bone Neoplasms; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Waldenstrom Macroglobulinemia

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

Topics: Bone Neoplasms; Humans; Lung Neoplasms; Male; Melphalan; Middle Aged; Multiple Myeloma

Topics: Bone Diseases; Bone Neoplasms; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neurologic Manifestations; Prednisone; Urethane

Topics: Adult; Aged; Bone Marrow Examination; Bone Neoplasms; Cerebrospinal Fluid Proteins; Cyclophosphamide; Female; Fractures, Spontaneous; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Metastasis; Plasma Cells; Polyradiculopathy; Radiography

Topics: Alkylating Agents; Bone Neoplasms; Cyclophosphamide; Dysgerminoma; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Mechlorethamine; Melphalan; Neoplasm Metastasis; Testicular Neoplasms

Topics: Adolescent; Adult; Alopecia; Bone Marrow Diseases; Bone Neoplasms; Cyclophosphamide; Female; Humans; Male; Melphalan; Sarcoma, Ewing; Vomiting

Topics: Adolescent; Bone Neoplasms; Chemotherapy, Cancer, Regional Perfusion; Child; Chondrosarcoma; Dogs; Femur; Fibula; Hemangiosarcoma; Humans; Melanoma; Melphalan; Mesenchymoma; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Sarcoma; Sarcoma, Ewing; Ulna; Uracil

Topics: Aorta; Aorta, Abdominal; Bone Neoplasms; Carotid Arteries; Chemotherapy, Cancer, Regional Perfusion; Chondrosarcoma; Dactinomycin; Dogs; Fibrosarcoma; Iliac Artery; Iliac Vein; Leiomyosarcoma; Liposarcoma; Lymphoma, Non-Hodgkin; Melphalan; Mesothelioma; Neoplasms; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Kaposi; Subclavian Artery; Vena Cava, Inferior

Topics: Bone Neoplasms; Elbow; Giant Cell Tumor of Bone; Giant Cell Tumors; Melphalan; Neoplasms; Neoplasms, Radiation-Induced; Pathology; Radiography; Sarcoma

Topics: Bone Neoplasms; Cobalt Isotopes; Dactinomycin; Drug Therapy; Humans; Mandible; Mandibular Neoplasms; Melphalan; Methotrexate; Neoplasms; Osteomyelitis; Osteosarcoma; Pathology; Radiography; Radium; Sarcoma