melphalan and Anemia

Multiple myeloma (MM) accounts for about 10% of all hematologic malignancies. The standard treatment with intermittent courses of melphalan and prednisone (MP) was introduced more than 30 years ago and, since then there has been little improvement in event-free and overall survival (EFS & OS). The aim of this article is to review: 1) the role of initial chemotherapy (ChT), maintenance treatment with alpha-interferon and salvage ChT, 2) the results of high-dose therapy (HDT) followed by allogeneic or autologous stem cell transplantation (allo-SCT and auto-SCT), and 3) the most important supportive measures.. The authors of this review have been actively working and contributing with original investigations on the treatment of MM during the last 15 years. In addition, the most relevant articles and recent abstracts published in journals covered by the Science Citation Index and Medline are also reviewed.. The importance of avoiding ChT in asymptomatic patients (smoldering MM) is emphasized. The criteria and patterns of response are reviewed. MP is still the standard initial ChT with a response rate of 50-60% and an OS of 2-3 years. Combination ChT usually increases the response rate but does not significantly influence survival when compared with MP. Exposure to melphalan should be avoided in patients in whom HDT followed by auto-SCT is planned, in order to not preclude the stem cell collection. The median response duration to initial ChT is 18 months. Interferon maintenance usually prolongs response duration but in most studies does not significantly influence survival (a large meta-analysis by the Myeloma Trialists' Collaborative Group in Oxford is being finished). In alkylating-resistant patients, the best rescue regimens are VBAD or VAD. In patients already resistant to VBAD or VAD and in those in whom these treatments are not feasible we recommend a conservative approach with alternate day prednisone and pulse cyclophosphamide. While HDT followed by autotransplantation is not recommended for patients with resistant relapse, patients with primary refractory disease seem to benefit from early myeloablative therapy. Although results from large randomized trials are still pending in order to establish whether early HDT intensification followed by auto-SCT is superior to continuing standard ChT in responding patients, the favorable experience with autotransplantation of the French Myeloma Intergroup supports this approach. However, although the complete response rate is higher with intensive therapy, the median duration of response is relatively short (median, 16 to 36 months), with no survival plateau. There are several ongoing trials comparing conventional ChT with HDT/autoSCT in order to identify the patients who are likely to benefit from one or another approach. With allo-SCT there is a transplant-related mortality ranging from 30 to 50% and also a high relapse rate in patients achieving CR. However, 10 to 20% of patients undergoing allo-SCT are long-term survivors (> 5 years) with no evidence of disease and, consequently, probably cured. The use of allogeneic peripheral blood stem cells (PBSC) in order to speed the engraftment and also the use of partially T-cell depleted PBSC which can decrease the incidence of graft-versus-host disease are promising approaches. In the setting of allo-SCT, donor lymphocyte infusion is an encouraging strategy in orde

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Contraindications; Diphosphonates; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Infection Control; Interferon-alpha; Kidney Failure, Chronic; Male; Melphalan; Multiple Myeloma; Myeloma Proteins; Osteolysis; Prednisone; Prognosis; Remission Induction; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous

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

Patients with benign monoclonal gammopathy or smouldering multiple myeloma should not be treated. The plasma cell labelling index utilizing tritiated thymidine or a monoclonal antibody to 5-bromo-2-deoxyuridine is helpful in differentiating patients with benign monoclonal gammopathy or smouldering myeloma from those with overt myeloma. Although combinations of chemotherapeutic agents seem to produce a greater number of objective responses than does melphalan-prednisone, a significant difference in survival has not been proved. Possibilities for future treatment include chemotherapy with large intravenous doses of melphalan, very small doses of cyclophosphamide or melphalan, the administration of hydroxyurea before chemotherapy, combination of interferon with alkylating agents, autologous bone marrow transplantation, and improvement of the soft-agar colony-forming assay for myeloma cells. The therapeutic use of monoclonal antibodies to plasma cell antigens may be possible in the future. Much more needs to be learned about the biologic basis of myeloma before real progress can be made.

Topics: Acute Kidney Injury; Anemia; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Blood Viscosity; Bone Diseases; Bone Marrow Transplantation; Drug Resistance; Humans; Hypercalcemia; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Prednisone; Spinal Cord Compression; Time Factors

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

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anemia; Anemia, Hemolytic, Autoimmune; Blood Urea Nitrogen; Glucocorticoids; Humans; Hypercalcemia; Immunoglobulins; Leukemia; Lymphoma; Melphalan; Multiple Myeloma; Myeloma Proteins; Prednisone; Waldenstrom Macroglobulinemia

Topics: Amyloid; Amyloidosis; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infections; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Prognosis; Pyelonephritis

Lenalidomide (Len) and dexamethasone (dex) therapy is a standard therapy in patients with multiple myeloma. Elderly or unfit patients may reduce Len or dex doses to prevent toxicities that lead to treatment discontinuation. However, there have been few studies evaluating the efficacy and safety of lower doses of Len and dex. We conducted a phase II study of 1.5-year low-dose Len and dex therapy following melphalan and prednisolone (MP), the number of which cycles was determined by a response within 9 cycles. The Len dose was 10 mg daily and the dex dose was 20 mg weekly, which were continued for 1.5 years. Twenty-one patients were enrolled. The median number of cycles of MP was 3 (range, 2-9). The overall response rate was 81% and a very good partial response or better was achieved in 33.3% of patients. The median follow-up time for survivors was 70.5 months (range, 42-83 months), the median progression-free survival (PFS) was 27 months (95% CI, 21-33 months), and the median overall survival was not reached. Grade 3 or 4 adverse events were observed in 28.6% of patients. In conclusion, the low-dose Len and dex therapy safely achieved comparable efficacies to the standard-dose regimen in elderly patients with newly diagnosed multiple myeloma. UMIN000007889.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Febrile Neutropenia; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Lenalidomide; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisolone; Progression-Free Survival; Remission Induction; Treatment Outcome; Young Adult

The phase 3 FIRST (Frontline Investigation of REVLIMID + Dexamethasone Versus Standard Thalidomide) trial demonstrated that lenalidomide plus low-dose dexamethasone (Rd) until disease progression (Rd continuous) is an effective treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Given genetic differences between Asian and Western populations, this subanalysis of the FIRST trial examined the safety and efficacy of Rd (given continuously or for 18 cycles [Rd18]) and MPT (melphalan, prednisone, thalidomide) in 114 Asian patients from Mainland China, South Korea and Taiwan. Efficacy and safety with Rd continuous in Asian patients were consistent with those in the overall study population. The overall response rates were 77·8% for Rd continuous, 57·5% for MPT and 65·8% for Rd18. The risk of progression or death was reduced by 39% with Rd continuous versus MPT and by 35% with Rd continuous versus Rd18. Rd continuous improved the 3-year survival rate compared with MPT (70·2% vs. 56·4%) and Rd18 (58·1%). Common grade 3/4 adverse events in the Rd continuous and MPT arms were neutropenia (25·0% vs. 43·6%), infection (19·4% vs. 28·2%) and anaemia (19·4% vs. 15·4%), respectively. Thromboembolic event rates were low, and no second primary malignancies were observed. Rd continuous is safe and effective in transplant-ineligible Asian patients with NDMM.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Asia; Asian People; Dexamethasone; Disease Progression; Disease-Free Survival; Female; Humans; Infections; Lenalidomide; Male; Melphalan; Middle Aged; Multiple Myeloma; Neutropenia; Prednisone; Remission Induction; Thalidomide; Treatment Outcome

Bortezomib synergizes with melphalan in preclinical and early clinical studies. Updated data from our phase 1/2 study assessing the safety and efficacy of bortezomib plus melphalan in relapsed/refractory multiple myeloma (MM) are presented. Bortezomib (0.7, 1.0, or 1.3 mg/m(2)) on days 1, 4, 8, and 11 and oral melphalan (0.025-0.25 mg/kg) on days 1-4 of a 28-day cycle were administered. Hematologic toxicities defined the maximum tolerated dose as bortezomib 1.0 mg/m(2) and melphalan 0.10 mg/kg. Because dose-limiting toxicities were attributed to the more myelosuppressive melphalan, cohorts 9 and 10 with higher bortezomib (1.3 mg/m(2)) and lower melphalan (0.025 and 0.10 mg/kg) doses were added. Responses occurred in 32/46 (70%) evaluable patients: two complete (4%), five near-complete (11%), 16 partial (35%), and nine minimal (20%). Complete and near-complete responses were observed only with higher bortezomib doses. Response rates were similar in patients with prior melphalan or bortezomib. Median progression-free survival was 9 months (range, 1-24), and overall survival was 32 months (range, 1-54). The most common grade 3/4 hematologic adverse events (AEs) were neutropenia (31%/0%), thrombocytopenia (25%/2%), and anemia (13%/0%). Grade 4 tumor lysis syndrome was reported in one patient. Fewer grade 3/4 hematologic AEs were reported in cohorts 9 and 10 than in cohorts receiving lower bortezomib and higher melphalan doses. In conclusion, bortezomib plus melphalan is a steroid- and immunomodulatory drug-free regimen that may provide a treatment alternative for elderly patients and patients with significant comorbidity.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Neutropenia; Pyrazines; Thrombocytopenia

Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7 months: 26 (26.3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40.4%) showed an improvement >50% (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28.4 and 26 months respectively: median survival of CR + PR patients was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the non-responders (log-rank test, P =0.002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR = 2.4) and not achieving any type of response, either partial or complete (HR = 3.9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Alkylating; Female; Follow-Up Studies; Humans; Leukocyte Count; Male; Melphalan; Middle Aged; Primary Myelofibrosis; Prognosis; Survival Rate; Treatment Outcome

The objectives of the present study were to determine the following: (a) the maximum tolerated dose (MTD) of melphalan using a 24-h continuous infusion; (b) the clinical toxicity; and (c) the pharmacokinetic characteristics of melphalan at each dose level. Twenty-one patients with refractory solid tumors were enrolled in the study. Melphalan, packaged in 3% sodium chloride, was administered i.v. over a 24-h period. Patients were assigned to one of three escalating dose levels of melphalan: (a) 20 mg/m2 (n = 5); (b) 30 mg/m2 (n = 7); and (c) 40 mg/m2 (n = 6). Each patient underwent pharmacokinetic evaluation during the first cycle of treatment. Melphalan concentrations in plasma were determined by high-performance liquid chromatography. Toxicity was evaluated after each course of chemotherapy. All of the patients were assessable for toxicity and pharmacokinetics, and 20 patients were assessable for response analysis. A total of 50 courses of melphalan was studied. The MTD was 30 mg/m2. The dose-limiting toxicity was neutropenia and thrombocytopenia. Hematotoxicity was reversible (nadir, 14-15 days; recovery, 3.5 and 12.5 days for 30 and 40 mg/m2, respectively), cumulative, and related to the administered dose and to the history of previous therapy. There were six episodes of neutropenic sepsis. Individual pharmacokinetic parameters were estimated using a Bayesian approach and linear elimination kinetics. Data were compatible with a one-compartment model. Relationships have been found between the area under the plasma concentration-time curve and doses and between Css and doses. Moreover, clearance, t1/2 elimination, and volume of distribution did not change statistically with dose, which suggests linear kinetics. Two partial responses were observed in patients with ovarian carcinoma or adenocarcinoma of unknown primary origin, and another patient had stabilization disease. In conclusion, melphalan MTD was determined to be 30 mg/m2 when administered as a 24-h infusion. Hematological toxicity was the dose-limiting toxicity. The most important nonhematological toxicity encountered was nausea and vomiting. The recommended dose for Phase II studies was 30 mg/m2.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Agents, Alkylating; Area Under Curve; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Melphalan; Middle Aged; Neoplasms; Neutropenia; Regression Analysis; Thrombocytopenia

With the aim of developing an effective therapy for heavily pretreated refractory MM outpatients, we evaluated the OPPEBVCAD regimen, a Hodgkin's disease-derived protocol that includes many drugs effective in MM administered in a sequential schedule. Twenty-two pts aged 42-72 years, with symptomatic highly-pretreated refractory (18 cases), or primary resistant MM (four cases. including two pts with plasma cell leukemia-PCL) received this therapy every 28 days (2-4 cycles, followed by a maintenance program). Therapeutic response (Chronic Leukemia-Myeloma Task Force criteria) and performance status (PS) and pain (W.H.O.) were evaluated. All of the pts were evaluable for response. There were 9 (40%) objective responses (OR: stabilization of blood counts and bone lesions, serum calcium normalization, 50% or more reduction in the concentration of serum monoclonal component (MC), 90% reduction in Bence-Jones proteinuria), 8 (36%) partial responses (PR: 25-50% reduction in serum MC), 1 no response or stable disease (NR), and 4 (18%) cases of progressive disease (PD). OR plus PR were 77%. Of the 4 primary resistant tumors (2 PCL and 2 MM), 2 achieved PR, 1 OR (a PCL case) and 1 progressed. Median survival was 15 months for responding pts (OR plus PR) and 4.5 months for non-responders (NR plus PD). PS and pain improved in 15 pts and did not change in 9. The most frequent side effects were cytopenias, with one drug related infective death. The OPPEBVCAD regimen proved to be an effective therapy for refractory relapsing or primary resistant MM: in responders (two-thirds of the pts), survival was prolonged by about 10 months. Its efficacy in anthracycline-treated pts, as well as the feasibility of using it on an outpatient basis without any continuous drug infusions, make this regimen a promising third line salvage therapy.

Topics: Adult; Aged; Agranulocytosis; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cause of Death; Drug Administration Schedule; Drug Resistance, Neoplasm; Epirubicin; Humans; Lomustine; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Procarbazine; Salvage Therapy; Survival Rate; Thrombocytopenia; Treatment Outcome; Vinblastine; Vincristine; Vindesine

The acute-phase response and anaemia of chronic disease are characterized by hypoferraemia associated with an increased ferritin synthesis, which might be mediated by the activated cytokine cascade.. We examined the prolonged effects of isolated limb perfusion (ILP) with recombinant human tumour necrosis factor alpha (rTNF), recombinant human interferon gamma (rIFN-gamma) and melphalan on interleukin (IL) 6 and acute-phase protein levels, iron status and serum transferrin receptor (sTfR) levels in 12 patients with melanoma or sarcoma. Patients were treated with ILP during 90 min after pretreatment with rIFN-gamma during 2 days.. After ILP, leakage of TNF resulted in systemic peak levels at 3 min followed by an increase in IL-6 with maximum levels at 4h. C-reactive protein (CRP) rose at 4 h to peak levels at day 2, whereas alpha 1-antitrypsin and alpha 1-acid glycoprotein increased to maximum levels at day 3. Albumin and transferrin levels decreased after ILP and recovered after day 2. Serum iron and sTfR levels decreased during pretreatment and after ILP to minimum levels at 8 h and day 1 respectively. This was associated with an increase in serum ferritin levels, which paralleled CRP values.. Our data point to a central role for the cytokine network in the modulation of iron metabolism in the acute-phase response and anaemia of chronic disease. TNF, possibly via induction of IL-6, and IFN-gamma induce hypoferraemia, which may in part result from a decrease in tissue iron release based on a primary stimulation of ferritin synthesis. The fall in sTfR levels may reflect an impaired erythroid growth and/or TfR expression mediated by TNF and IFN-gamma.

Topics: Acute-Phase Proteins; Adult; Aged; alpha 1-Antitrypsin; Anemia; C-Reactive Protein; Chemotherapy, Cancer, Regional Perfusion; Female; Ferritins; Humans; Interferon-gamma; Interleukin-6; Iron; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Metastasis; Orosomucoid; Receptors, Transferrin; Recombinant Proteins; Sarcoma; Serum Albumin; Time Factors; Transferrin; Tumor Necrosis Factor-alpha

The use of intravenous melphalan at higher doses is limited by severe myelosuppression. It was postulated that GM-CSF would permit the use of higher dose melphalan with only moderate myelosuppression easily manageable in an outpatient setting. Therefore, a phase I study of intravenous melphalan utilizing GM-CSF (recombinant granulocyte-macrophage colony-stimulating factor) support was initiated. Intravenous melphalan at doses of 15-45 mg/m2 was administered every 28 days. GM-CSF was utilized at doses of 10-20 micrograms/kg/day subcutaneously Days 2-21 on a 28-day cycle. Twenty-five patients received 53 courses of therapy. The dose-limiting toxicities were severe or life-threatening granulocytopenia and thrombocytopenia. Utilizing 20 micrograms/kg/day GM-CSF, the maximum tolerated dose (MTD) of melphalan is 30 mg/m2 and, with 10 mg/kg/day GM-CSF, the maximum tolerated melphalan dose is only 20 mg/m2. One patient with ovarian cancer achieved a partial response. Because the reported MTD of intravenous melphalan without GM-CSF is 30 mg/m2, GM-CSF has not allowed sufficient escalation of the intravenous melphalan dose for routine outpatient use.

Topics: Adenocarcinoma; Adult; Agranulocytosis; Anemia; Drug Evaluation; Endometrial Neoplasms; Female; Genital Neoplasms, Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leiomyosarcoma; Melphalan; Ovarian Neoplasms; Recombinant Proteins; Thrombocytopenia

From May 1978 until November 1980, 169 previously untreated patients with advanced epithelial ovarian cancer were entered into a prospective randomized clinical trial comparing the combination of hexamethylmelamine, Adriamycin, and cyclophosphamide (HAC) to a combination of melphalan and cis-platinum. Eleven patients were excluded from analysis and another 5 patients were excluded from response analysis. Of 153 patients evaluable for response, there were 47, or 30.7%, complete responders (all determined surgically), 6 partial responders, and 100 nonresponders. The response rate for the HAC group was 31% and for the melphalan-platinum group was 37.8%. The overall response rate was 34.6%. Residual tumor diameter (less than or greater than 2 cm) exerted a statistically significant effect on response--47.8 vs 24.4%. Of the 47 complete responders, 7, or 14.9%, have relapsed, with the median duration of remission of 44+ months. Of the 158 patients evaluable for survival, 90 patients have died, with a median survival time of 27.9 months (HAC = 26.4 months, melphalan-platinum = 29.6 months). Age, FIGO stage, histologic grade, and residual disease all exerted a significant effect on survival time. Second-line therapy in the treatment failures was of no benefit. Hematologic toxicity was greater in the melphalan-platinum group. Gastrointestinal toxicity was severe in both groups. Other toxicities were minor and infrequent.

Topics: Adult; Altretamine; Anemia; Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leukopenia; Melphalan; Middle Aged; Ovarian Neoplasms; Prospective Studies; Random Allocation; Thrombocytopenia

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 effect of certain disease parameters on remission and survial time was evaluated in 482 patients with multiple myeloma treated with intermittent courses of melphalan-prednisone combinations. Increasing degrees of anemia, hypercalcemia, azotemia, and high serum myeloma protein levels were associated with progressive lifespan shortening. The short survival of patients with anemia and hypercalcemia was associated with short remissions in responding patients with these abnormalities. The extent of tumor mass was defined from specific laboratory parameters reported by Durie to be associated with large numbers of plasma cells. More advanced stages of myeloma were associated with higher frequencies and degrees of normal immunoglobulin depression. The response rate was not affected by the tumor mass grade, but increasing tumor mass was associated with a shorter lifespan. Greater degrees of tumor reduction were associated with longer remission and survival times. Patients in whom a marked tumor reduction was rapid had shorter survival and remission times than patients who responded more slowly.

Topics: Aged; Anemia; Drug Therapy, Combination; Female; Humans; Hypercalcemia; Immunoglobulins; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Plasma Cells; Prednisone; Prognosis; Remission, Spontaneous; Serum Albumin; Time Factors; Uremia

Topics: Amyloid; Amyloidosis; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infections; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Prognosis; Pyelonephritis

For treatment of metastatic lung lesions there was used the method of isolated chemoperfusion in combination with metastasectomy. The study included 74 patients (mean age 43 ± 13.4 years). There were performed 99 normothermic isolated chemoperfusions of the lung: with melphalan (39) and cisplatin (60). During surgery there were no lethality outcomes. In the immediate postoperative period it was recorded 1 (1.4%) death developed in 3 days after surgery. The cause of this death was postperfusion lung edema accompanied by increase of signs of respiratory insufficiency. There were following complications after isolated chemoperfusions of the lung: anemia--23 (23.1%), nausea--13 (13.1%), vomiting--5 (5.1%), atrial fibrillation--10 (10.1%), pneumonia-2 (2.0%), pulmonary infarction--2 (2.0%), chylothorax--1 (1.0%), pneumothorax--29 (29.3%), emphysema of soft tissues of the chest wall 73 (73.7% ). Thus isolated chemoperfusion of the lung with melphalan or cisplatin is a procedure reproducible and relatively safe.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Chemotherapy, Cancer, Regional Perfusion; Chylothorax; Cisplatin; Female; Humans; Lung Neoplasms; Male; Melphalan; Metastasectomy; Middle Aged; Nausea; Pneumothorax; Respiratory Insufficiency; Subcutaneous Emphysema; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Causality; Cladribine; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Female; Humans; Lenalidomide; Leukemia, Large Granular Lymphocytic; Male; Melphalan; Methotrexate; Middle Aged; Multiple Myeloma; Neutropenia; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Prednisone; Protease Inhibitors; Pyrazines; Registries; Retrospective Studies; Thalidomide

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Female; Fractures, Spontaneous; Hip Fractures; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Melphalan; Multiple Myeloma; Myeloma Proteins; Neoplastic Cells, Circulating; Prednisone

Immunoblastic lymphadenopathy is a recently described lymphoproliferative disorder, presumably of B-cell origin. It is characterized by regional or generalized lymphadenopathy, usually associated with hypergammaglobulinemia or dysproteinemia. Other findings may be hepatosplenomegaly, dermatitis, fever, malaise, weight loss, and various altered immunologic reactions. Histologically, the involved lymph nodes show immunoblast, plasmacytoid, and plasma cell proliferation. This may be extranodal as well. The case reported here is one of the few followed up prospectively. The patient's purpuric eruption was an apparent manifestation of a type II mixed cryoglobulinemia. Differing from what has usually been reported, we noted hypogammaglobulinemia and findings in part of altered cell-mediated immunity. Despite leukopenia and anemia there were no infectious episodes. Although a satisfactory treatment regimen has not been established, there was beneficial response to prednisone and short courses of melphalan.

Topics: Allopurinol; Anemia; B-Lymphocytes; Cryoglobulins; Female; Humans; Leukopenia; Lymphatic Diseases; Melphalan; Middle Aged; Paraproteinemias; Prednisone; Purpura, Hyperglobulinemic

Topics: Adult; Age Factors; Aged; Anemia; Blood Urea Nitrogen; Calcium; Cyclophosphamide; Drug Evaluation; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Prognosis; Remission, Spontaneous; Serum Albumin; Serum Globulins; Time Factors; Uric Acid

The experience of a solo practitioner suggests that the incidence of multiple myeloma is higher than the widely reported figure of 2.7/100,000. Only by early recognition and treatment will the survival rate be increased. Measurement of the sedimentation rate may be helpful in spotting the disease, for a rapid rate in patients with bone pain and anemia suggests multiple myeloma.

Topics: Adult; Anemia; Blood Sedimentation; Bone Diseases; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Pain; Prednisone

Patients with asymptomatic or smoldering multiple myeloma should not be treated but should be observed closely for progression. For symptomatic myeloma, chemotherapy is indicated. Melphalan, the agent of choice, should be given with prednisone for 1 week of every 6 weeks, If melphalan brings no response, or response and then relapse, cyclophosphamide (Cytoxan) should be give intravenously every 4 weeks or orally every day. BCNU, CCNU, and doxorubicin (Adriamycin) have also shown activity in myeloma. Hypercalcemia occurs in one-third of patients and should be countered with hydration, corticosteroids, Neutra-Phos, or mithramycin. Long-term hemodialysis has achieved some success. The combination of sodium flouride and calcium carbonate produces new bone formation; it seems a useful adjunct in treatment for myelomatous bone disease. Radiation should be utilized only for severe, localized pain or for solitary lesions. Survival with multiple myeloma varies, mean durations being 2 to 3 years. Multivariate analysis indicates that serum creatinine and calcium levels are the most significant indicators regarding 2-year survival. We have found monoclonal proteinuria not significantly more frequent with renal insufficiency than with normal renal function, renal insufficiency not significantly more frequent with lambda than with kappa chains, and survival not significantly greater with IgG myeloma than with IgA.

Topics: Anemia; Bacterial Infections; BCG Vaccine; Carmustine; Cyclophosphamide; Fractures, Bone; Humans; Hypercalcemia; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Mycobacterium bovis; Prognosis

Topics: Anemia; Blood Cell Count; Bone Marrow; Bone Marrow Cells; Cyclophosphamide; Edema; Female; Hemoglobins; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lymphography; Male; Melphalan; Middle Aged; Waldenstrom Macroglobulinemia

Topics: Anemia; Fluorouracil; Humans; Leukopenia; Melphalan; Nitrogen Mustard Compounds; Stomach Neoplasms; Thiotepa; Thrombocytopenia

Topics: Adolescent; Adult; Aged; Anemia; Cardiomyopathies; Chemotherapy, Cancer, Regional Perfusion; Child; Cyclophosphamide; Electrocardiography; Humans; Leg; Leukopenia; Melphalan; Middle Aged; Neoplasms; Tachycardia; Thiotepa; Vascular Diseases

Topics: Adult; Aged; Amyloidosis; Anemia; Bence Jones Protein; Cyclophosphamide; Female; gamma-Globulins; Humans; Hypercalcemia; Immunochemistry; Immunoglobulin M; Male; Melphalan; Middle Aged; Multiple Myeloma; Uremia

Topics: Anemia; Bence Jones Protein; Cyclophosphamide; Humans; Hypercalcemia; Immunoglobulin M; Kidney Failure, Chronic; Melphalan; Multiple Myeloma

Topics: Anemia; Humans; Hypercalcemia; Melphalan; Multiple Myeloma; Osteoporosis

Topics: Adult; Aged; Anemia; Bence Jones Protein; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Serum Albumin

Topics: Anemia; Bence Jones Protein; Female; Humans; Hypercalcemia; Male; Melphalan; Multiple Myeloma; Prognosis; Serum Globulins; Uremia; Urethane

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

Topics: Anemia; Cyclophosphamide; Humans; Leukopenia; Melphalan; Multiple Myeloma; Prednisone; Urethane