melphalan and Sepsis

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Clostridium Infections; Clostridium perfringens; Embolization, Therapeutic; Fatal Outcome; Hemolysis; Humans; Liver Neoplasms; Lung Neoplasms; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasms, Multiple Primary; Prednisone; Sepsis

High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of > or = 2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Drug Resistance, Neoplasm; Etoposide; Female; Follow-Up Studies; Gastrointestinal Diseases; Hodgkin Disease; Humans; Ifosfamide; Kaplan-Meier Estimate; Lymphoma; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Neutropenia; Peripheral Blood Stem Cell Transplantation; Recurrence; Remission Induction; Salvage Therapy; Sepsis; Survival Rate; Transplantation, Autologous; Treatment Outcome

This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma.. One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival.. Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012).. Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bronchiolitis Obliterans; Chemotherapy, Adjuvant; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Infant; Kidney Diseases; Life Tables; Male; Melphalan; Neoplasm Metastasis; Radiotherapy, Adjuvant; Remission Induction; Rhabdomyosarcoma; Sepsis; Soft Tissue Neoplasms; Survival Analysis; Treatment Outcome; Vincristine

The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483-487.

Topics: Antigens, CD34; Antineoplastic Agents, Alkylating; beta 2-Microglobulin; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Evaluation Studies as Topic; Fever; Graft Survival; Humans; Lymphocyte Count; Melphalan; Multiple Myeloma; Pneumonia; Prognosis; Sepsis; Stomatitis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

Autologous stem cell transplantation after high-dose melphalan for the treatment with multiple myeloma has resulted in prolonged progression-free survival and overall survival in patients under 65 years. We have examined the role of autologous transplantation in 17 patients with multiple myeloma over 65 years at our centre using a matched pair analysis with younger patients. The median age of this cohort of patients over 65 years was 67 years (65-74) and their outcome and transplant-related morbidity was compared with 17 younger pair mates with a median age of 55 years (31-64). Sixteen patients received high-dose melphalan, and one received busulphan with autologous stem cell rescue. The high-dose therapy was well tolerated in both elderly patients and the matched pairs, with comparable time to recover neutrophils and platelets. Treatment-related mortality also did not differ significantly in both the groups. Median overall survival of the elderly patients was 3.59 years similar to 3.01 years of the pair mates (P = 0.92). Autologous stem cell transplantation after high-dose melphalan conditioning was equally well tolerated in groups of patients above and below 65 years. There was no difference in relapse rate, OS and myelotoxicity in both the groups. These findings suggest that advanced age should not be an exclusion criterion from autologous transplant programmes. Bone Marrow Transplantation (2000) 25, 533-539.

Topics: Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carmustine; Chemical and Drug Induced Liver Injury; Cohort Studies; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Graft Survival; Heart Diseases; Hematopoietic Stem Cell Mobilization; Hospitalization; Humans; Interferons; Kidney Diseases; Male; Matched-Pair Analysis; Melphalan; Methylprednisolone; Middle Aged; Multiple Myeloma; Neutropenia; Neutrophils; Platelet Count; Recurrence; Sepsis; Survival Rate; Thrombocytopenia; Transplantation, Autologous; Vincristine

From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited.

Topics: Adolescent; Bone Marrow Transplantation; Cataract; Child; Child, Preschool; Disease-Free Survival; Female; Fever; Follow-Up Studies; Gonadal Disorders; Graft Survival; Human Growth Hormone; Humans; Infant; Male; Melphalan; Mouth Mucosa; Neutrophils; Platelet Count; Pneumocystis Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Sepsis; Stomatitis; Survival Rate; Thyroxine; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

High-dose chemotherapy with autologous stem cell rescue (ASCR) is a key component of high-risk neuroblastoma therapy. Resources required to support patients treated with ASCR conditioning regimens [carboplatin/etoposide/melphalan (CEM) and busulfan/melphalan (BuMel)] have not been directly compared.. An administrative database was used to analyze resource utilization and outcomes in a cohort of high-risk neuroblastoma patients. Patients were followed for 60 days from start of conditioning or until death. Length of hospitalization, length of intensive care unit (ICU) level of care, incidence of sepsis and sinusoidal obstruction syndrome (SOS), and duration of use of specific supportive care resources were analyzed.. Six of 171 CEM patients and zero of 59 BuMel patients died during the study period (P = 0.34). Duration of hospitalization was longer following BuMel (median 35 vs. 31 days; P = 0.01); however, there was no difference in duration of ICU-level care. Antibiotic use was longer following CEM (median 19 vs. 15 days; P = 0.01), as was antihypertensive use (median 5 vs. 1.6 days; P = 0.0024). Duration of opiate and nonnarcotic analgesic use was longer following CEM early in the study period. Resources consistent with a diagnosis of SOS were used in a higher proportion of BuMel patients. A higher proportion of BuMel treated patients required mechanical ventilation (17% vs. 6%; P = 0.03).. We used administrative billing data to compare resources associated with ASCR conditioning regimens. CEM patients required more extended use of analgesics, antibiotics, and antihypertensives, while duration of hospitalization was longer, and SOS and the use of mechanical ventilation were more frequent following BuMel.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Autografts; Busulfan; Carboplatin; Child; Child, Preschool; Critical Care; Databases, Factual; Etoposide; Female; Follow-Up Studies; Humans; Incidence; Infant; Length of Stay; Male; Melphalan; Neuroblastoma; Peripheral Blood Stem Cell Transplantation; Sepsis; Stem Cells; Transplantation Conditioning; United States

Topics: Capillary Leak Syndrome; Combined Modality Therapy; Drug Therapy, Combination; Humans; Hypotension; Immunoglobulins, Intravenous; Immunosuppressive Agents; Intestinal Perforation; Male; Melphalan; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Prednisone; Sepsis; Sympathomimetics; Terbutaline; Theophylline

Intermittent courses of melphalan and prednisone is still the standard chemotherapy for the initial treatment of multiple myeloma (MM) in patients who cannot undergo high-dose chemotherapy/radiotherapy with either allogeneic or autologous stem cell transplantation. However, the absorption of the drug from the gastrointestinal tract is highly variable from patient to patient and therefore, different plasma levels of the drug are reached in the blood of individual MM patients. In order to overcome this limitation we decided to use intermediate dose (15-30 mg/m2, day 1) intravenous melphalan in resistant or relapsing MM patients as well as in untreated patients not eligible for a more aggressive protocol. Moreover, considering the good results obtained by other investigators using dexamethasone alone or associated with interferon in the treatment of resistant or relapsing MM patients, dexamethasone (40 mg total dose, day 1) and the lymphoblastoid alpha interferon (3 MU, 3 times a week x 3 weeks, from day 8 to day 26 of each course) were added to intravenous melphalan. Courses were repeated every 5 weeks for a total of 6 cycles. We treated 62 MM patients obtaining a response (defined as reduction > 25% of the initial monoclonal component value associated with disappearance of the clinical symptoms) in 38 out 62 evaluable patients (61%) and stable disease (defined as a decrease of < 25% in the base-line serum monoclonal component level with disappearance of all symptoms present at diagnosis) in 9 (14.5%) more patients. The overall median response duration was 14 months and the overall median survival duration (from the time of inclusion in this protocol) for the 62 patients entered into the study was 34 months. No severe (Grade 3-4 of the WHO) hematological as well as non hematological toxicities were observed. This lack of severe toxicity allowed us to administer the drugs on an outpatient basis. In conclusion, the overall response and the low grade of toxicity in this category of patients are encouraging and suggest that this protocol is both effective and safe treatment for high risk MM patients.

Topics: Actuarial Analysis; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Dexamethasone; Disease-Free Survival; Drug Evaluation; Drug Resistance; Drug Therapy, Combination; Female; Humans; Interferon-alpha; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Recurrence; Risk Factors; Sepsis; Survival Rate; Thrombocytopenia; Treatment Outcome

Causes of treatment-related death were studied amongst 138 patients with acute myeloid (n = 90) or lymphoblastic (n = 48) leukemia allografted from HLA-identical siblings in first (n = 107) or second (n = 31) remission after a conditioning regimen comprising 110 mg/m2 melphalan and 1050 cGy single-fraction total-body irradiation (TBI) prescribed as maximum lung dose. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (n = 78) or cyclosporine-methotrexate (n = 60). Eighty-one patients died of causes other than relapse 16-2917 days (median 77) after transplantation. The actuarial probability of non-relapse mortality was 62% at 5 years. The major primary causes of death were pneumonitis (n = 38, 47%), GVHD (n = 18, 22%), and sepsis (n = 11, 14%). Pneumonitis contributed to 42 of the deaths (52%), and its etiology was infective (n = 27), idiopathic (n = 14), or a combination of the two (n = 1). On multivariate analysis, GVHD prophylaxis with cyclosporine alone was associated with a higher overall toxic death rate. The use of cyclosporine alone and a low infused cell dose (<2.5 x 10(8) total nucleated cells/kg or <0.6 x 10(8) mononuclear cells/kg) were associated with a higher risk of death from pneumonitis. We conclude that the use of cyclosporine alone as GVHD prophylaxis is associated with increased transplant-related toxicity, and the addition of methotrexate and infusion of a higher number of cells decrease the incidence of fatal pneumonitis.

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Child; Child, Preschool; Female; Graft vs Host Disease; Humans; Leukemia, Myeloid; Lung Diseases, Interstitial; Male; Melphalan; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sepsis; Transplantation Conditioning; Whole-Body Irradiation

To analyze the mechanism of vasodilation and circulatory shock occurring in patients who are treated with isolated limb perfusion with melphalan and recombinant tumor necrosis factor (TNF)-alpha for locally advanced malignant tumors. To determine the role of nitric oxide, if any, by measuring plasma nitrite and nitrate concentrations.. Observational survey.. A 12-bed surgical intensive care unit in a university referral hospital.. Eight patients treated with hyperthermic isolated limb perfusion.. Ninety minutes of hyperthermic isolated limb perfusion with recombinant TNF-alpha (3 or 4 mg) and melphalan (10 to 13 mg/L limb volume).. All patients developed sepsis syndrome due to leakage of recombinant TNF-alpha from the perfusion circuit to the systemic circulation. Despite the presence of very high systemic TNF-alpha concentrations during and immediately after perfusion, and despite definite signs of hyperdynamic circulatory shock (increased heart rate, increased cardiac index, decreased systemic vascular resistance), nitrite and nitrate concentrations, as measured in plasma at several time points, were not increased.. The hypothesis that in humans, TNF-alpha induces vasodilation and shock through activation of inducible nitric-oxide synthase and subsequent formation of excessive quantities of nitric oxide is not substantiated by our results. Normal nitric oxide metabolite concentrations were found in the presence of high TNF-alpha concentrations and shock. Other mechanisms that do not involve the nitric oxide pathway are likely to play a role in the generation of hypotension and septic shock in this setting.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Hemodynamics; Humans; Male; Melphalan; Middle Aged; Neoplasms; Nitrates; Nitric Oxide; Nitrites; Sepsis; Shock; Tumor Necrosis Factor-alpha

A study in 10 patients (eight male, two female; mean age 61.9 +/- 10.7 years) suffering from multiple myeloma (MM) and end-stage renal failure (ESRF) is detailed. Continuous ambulatory peritoneal dialysis (CAPD) was the preferred mode of chronic dialysis in all the patients. Survival after diagnosis was 32.2 +/- 23.9 months. Survival after starting dialysis was 24.6 +/- 20.6 months. All patients on CAPD were adequately dialyzed and in good fluid control. Peritonitis was the main problem on CAPD (one episode per 5.6 patient-months). The majority of peritonitis episodes responded to intraperitoneal antibiotic therapy. One patient with Staphylococcus aureus peritonitis, septicemia, and neutropenia secondary to chemotherapy, died. Recommendations for prophylaxis and treatment of peritonitis are given. Three patients were transferred to hemodialysis. The use of subclavian vein catheters during hemodialysis was associated with a high incidence of gram-positive septicemia. Alkylating agent-based chemotherapy resulted in hematological responses in five patients. Survival after diagnosis in those responders was 47.4 +/- 25.6 months, compared with 17.0 +/- 7.2 months in the nonresponders (P less than 0.05). All responders subsequently relapsed. Four patients died with progressive myeloma. Bone marrow suppression resulted in a high blood transfusion requirement, neutropenia, and thrombocytopenia associated with bleeding into the gastrointestinal tract and central nervous system. Uremic myeloma patients can be adequately dialyzed using CAPD. Those patients who do not have an initial hematological response have a poor prognosis.

Topics: Adult; Aged; Cyclophosphamide; Female; Humans; Kidney Failure, Chronic; Length of Stay; Male; Melphalan; Middle Aged; Multiple Myeloma; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prednisolone; Sepsis; Staphylococcal Infections; Survival Rate

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Drug Synergism; Female; Humans; Interferon Type I; Leukopenia; Male; Melphalan; Middle Aged; Multiple Myeloma; Myocardial Infarction; Prednisone; Sepsis

Described here is a 59 year old man with dermatomyositis and hypogammaglobulinemia. His muscle power improved after corticosteroid therapy, but extensive amyloidosis and repeated infections appeared. Bone marrow morphology suggested multiple myeloma, but treatment with cytotoxic drugs had no beneficial effect on the amyloidosis. Because of rapid progression of the amyloidosis and further infections, cytotoxic drug therapy was stopped, corticosteroid dosage was decreased, and supplementary immunoglobulin therapy was instituted. The infections occurred less frequently and the amyloidosis appeared to regress. This case suggests that immunosuppressive therapy may exacerbate amyloidosis. The literature is reviewed, and the possible role of humoral immunodeficiency in the pathogenesis of amyloidosis is discussed. It is suggested that supplementary immunoglobulin may be beneficial in amyloidosis.

Topics: Agammaglobulinemia; Amyloidosis; Bence Jones Protein; Dermatomyositis; gamma-Globulins; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Procarbazine; Sepsis; Skin Tests

Topics: Chemotherapy, Cancer, Regional Perfusion; Coccidioidomycosis; Dactinomycin; Drug Hypersensitivity; Drug Therapy; Hematologic Diseases; Humans; Melanoma; Melphalan; Mycetoma; Neoplasms; Sarcoma; Sepsis; Toxicology