melphalan and Acute-Kidney-Injury

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Chronic Disease; Combined Modality Therapy; Dexamethasone; Down-Regulation; Doxorubicin; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin lambda-Chains; Kidney Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Pyrazines; Remission Induction; Renal Dialysis; Transplantation, Autologous

A dramatic improvement in the prognosis of multiple myeloma has been obtained since treatment with alkylating agents was introduced in the sixties. In recent years much effort has been made to ameliorate the obtained results by employing polychemotherapy schedules of treatment. However, no significant improvements with respect to the conventional melphalan-prednisone treatment, in terms of survival duration, have been observed. New therapeutic approaches, such as the use of biological response modifiers and the autologous or allogeneic bone marrow transplantation offer new perspectives for multiple myeloma patients. In this paper we discuss current trends in the therapy of multiple myeloma and of related complications.

Topics: Acute Kidney Injury; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Humans; Hypercalcemia; Interferon Type I; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Prednisone; Recurrence

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

We conducted a phase I-II study of transplantation conditioning with clofarabine-melphalan-alemtuzumab for patients with advanced hematologic malignancies. Ten patients were accrued to the phase I portion, which utilized an accelerated titration design. No dose-limiting toxicity was observed, and clofarabine 40 mg/m(2) × 5, melphalan 140 mg/m(2) × 1, and alemtuzumab 20 mg × 5 was adopted for the phase II study, which accrued 72 patients. Median age was 54 years. There were 44 patients with acute myelogenous leukemia or myelodysplastic syndromes, 27 with non-Hodgkin lymphoma, and nine patients with other hematologic malignancies. The largest subgroup of 35 patients had American Society for Blood and Marrow Transplantation high-risk, active disease. All evaluable patients engrafted with a median time to neutrophil and platelet recovery of 10 and 18 days, respectively. The cumulative incidence of treatment-related mortality was 26% at 1 year. Cumulative incidence of relapse was 29% at 1 year. Overall survival was 80% (95% confidence interval [CI], 71-89) at 100 days and 59% (95% CI, 47-71) at 1 year. Progression-free-survival was 45% (95% CI, 33-67) at 1 year. Rapid-onset renal failure was the main toxicity in the phase II study and more frequent in older patients and those with baseline decrease in glomerular filtration rate. Grade 3-5 renal toxicity was observed in 16 of 74 patients (21%) treated at the phase II doses. Clofarabine-melphalan-alemtuzumab conditioning yields promising response and duration of response, but renal toxicity poses a considerable risk particularly in older patients.

Topics: Acute Kidney Injury; Adenine Nucleotides; Adult; Age Factors; Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Arabinonucleosides; Clofarabine; Female; Glomerular Filtration Rate; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Recurrence; Risk; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous

During March 1980 to February 1982, 73 out of 80 patients in renal failure admitted to the fourth MRC myelomatosis trial were managed by a planned policy of high fluid intake (greater than or equal to 3 1/24 h) in addition to receiving one of the two chemotherapeutic regimens being tested in the main trial. Patients were also randomised to receive either sodium bicarbonate to render their urine neutral or no supplement. Follow up continued till death or to April 1983. Of 49 patients who survived more than 100 days, 39 achieved reversal of their renal failure (18 complete, 21 partial). Recovery of renal function, as assessed by a fall in the serum creatinine concentration, was achieved even when light chain proteinuria persisted. Partial recovery of renal function was associated with prolonged useful life in several patients. In only 14 of the 80 patients studied was death directly attributable to renal failure. Survival of patients in the study was appreciably better than in equivalent groups of patients in other MRC trials in which less stringent policies of fluid intake were used. Patients randomised to receive alkali fared marginally better than the others, but the difference was not significant. These results show that in many cases patients with myelomatosis who develop renal failure may have this complication reversed by taking a high fluid intake. Furthermore, though light chain is an essential component of renal disease in these patients, other factors are also important and are accessible to treatment.

Topics: Acute Kidney Injury; Adult; Aged; Bicarbonates; Clinical Trials as Topic; Cyclophosphamide; Fluid Therapy; Humans; Melphalan; Middle Aged; Multiple Myeloma; Sodium Bicarbonate; Vincristine

Acute kidney injury (AKI) is a common complication after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with light chain (AL) amyloidosis. However, its incidence, predictors and outcomes are not well known.. This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT. AKI was defined as an increase in serum creatinine to ≥1.5 times the baseline occurring within the first 30 days of HDM/SCT.. The median age was 58 years (range: 30-77). Kidney and cardiac involvement were present in 86.1% and 56.8%, respectively. The median estimated glomerular filtration rate (eGFR) was 83.5 mL/min/1.73 m2 (range: 9-213) and proteinuria was 2899 mg/day (range: 0-19 966). AKI occurred in 29.1% of patients. Dialysis was initiated in 15 patients (6.7%) and of these 12 (80%) were able to discontinue dialysis. Most of the episodes of AKI occurred within the first 2 weeks; with a median follow-up of 4.5 years (range: 0.1-16.5), AKI was associated with increased overall mortality [hazard rato (HR) = 4.53, 95% confidence interval (CI) 2-10.23]. The 10-year overall survival was 87.1% without AKI, versus 56.9% with AKI. AKI was also associated with an increased risk for end-stage kidney disease (ESKD) (HR = 4.6, 95% CI 1.44-14.38). The risk of developing ESKD at 10 years was 18.9% with AKI, versus 8.1% without AKI. Several risk factors were found and using multivariate logistic regression, a prediction model was developed that included three readily available variables: eGFR <60 mL/min/1.73 m2, interventricular septal thickness in diastole >12 mm and albumin <3 g/dL. This model was able to predict AKI development with an area under the curve of 0.8.. AKI is common in the post-HDM/SCT period and it leads to increased risk for ESKD and death. Our prediction model is an easily deployable tool in clinical settings as part of the discussion with patients who are being prepared for HDM/SCT.

Topics: Acute Kidney Injury; Amyloidosis; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney Failure, Chronic; Melphalan; Middle Aged; Renal Dialysis; Retrospective Studies; Risk Factors; Transplantation, Autologous

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

Topics: Acute Kidney Injury; Aged, 80 and over; Anti-Infective Agents; Antineoplastic Agents, Alkylating; Critical Care; Drug Interactions; Fatal Outcome; Female; Humans; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Thrombotic thrombocytopenic purpura (TTP) is a particularly serious form of thrombotic microangiopathy (TMA) due to the risk of multiple organ dysfunction. Several etiological factors such as infection, auto-immune disease, certain medications and cancers have been associated with TTP.. A 74-year-old hypertensive woman with a history of thromboembolic disease was hospitalized for acute kidney injury (AKI) associated with pneumonia. Initial investigations were suggestive of Pneumocystis jirovecii infection and myeloma cast nephropathy. Several days later, the patient presented features of TTP. Von Willebrand factor-cleaving protease activity was less than 5% with a high level of IgG antibody directed against ADAMTS13. Treatment consisted of monthly 4-day cycles of dexamethasone and melphalan in combination with plasmapheresis and resulted in a favorable outcome. Three years after ceasing treatment, the patient presented no signs of hemolysis, but required chronic hemodialysis.. The association of TMA, especially TTP, and multiple myeloma is exceptional. The authors report such a case that induced irreversible renal damage, but with stable clinical and laboratory parameters with a follow-up of 4 years.

Topics: Acute Kidney Injury; ADAM Proteins; ADAMTS13 Protein; Aged; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Dexamethasone; Female; Humans; Immunoglobulin G; Melphalan; Multiple Myeloma; Plasmapheresis; Purpura, Thrombotic Thrombocytopenic; Renal Dialysis; Time Factors; Treatment Outcome

The presence of renal failure in patients with multiple myeloma (MM) has been considered an ominous prognostic factor associated with a significantly decreased life expectancy. The prognostic factors have seldom been analyzed to predict discontinuation of hemodialysis (HD) therapy in MM patients with renal failure after HD initiation. It is clinically very important to predict whether HD can be discontinued after introducing HD in such patients.. All medical and HD records were reviewed in MM patients who underwent HD in the National Center for Global Health and Medicine Hospital between January 1995 and May 2009. Thirty-two patients with MM had undergone HD. The clinical features and the factors that might be associated with recovery of renal function leading to discontinuation of HD in MM patients with severe renal failure were examined.. The factors associated with recovery of renal function and discontinuation of HD were: low International Staging System (ISS) score (p = 0.0034); high response to chemotherapy (p = 0.036); low serum Ca (p = 0.006); low Cr (p = 0.019), and low serum β₂-microglobulin (sβ₂M) (p = 0.002). On multivariate analysis, low serum Ca and sβ₂M were significantly associated with HD discontinuation. Moreover, discontinuing HD was the significant factor associated with improved overall survival in MM patients who required HD at least once.. sβ₂M and Ca were the laboratory parameters that were significant, independent prognostic factors for predicting the probability of recovery from severe renal failure and discontinuation of HD in MM patients who needed HD at least once.

Topics: Acute Kidney Injury; Aged; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Biomarkers; Calcium; Creatinine; Dexamethasone; Doxorubicin; Female; Humans; Kidney; Male; Melphalan; Middle Aged; Multiple Myeloma; Multivariate Analysis; Nitrosourea Compounds; Prednisolone; Prognosis; Recovery of Function; Renal Dialysis; Survival Analysis; Treatment Outcome; Vincristine

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Combined Modality Therapy; Etoposide; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Male; Melphalan; Neuroblastoma; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome; Tumor Lysis Syndrome

A 45-year-old woman was referred to our hospital with acute renal failure and pyrexia. In August 2005, the patient was diagnosed with IgA-λ type multiple myeloma with chromosome 13 deletion, and received three cycles of vinclistine, adriamycin and dexamethasone followed by high-dose melphalan-based autologous peripheral stem cell transplantation: this resulted in remission 2 months before admission to our hospital. Serum IgA concentration was within the normal limit, but an excess of myeloma cells in bone marrow was confirmed. Immunoelectrophoresis revealed BJP-λ production with no IgA-λ. The patient received several courses of chemotherapy with mechanical ventilation and regular hemodialysis. The progression of the illness was rapid: multiple organ failure promptly developed and the patient died 2 months after admission. Autopsy revealed deposition of light chain λ protein in multiple organs. We report this unusual case of aggressive myeloma recognized shortly after successful autologous transplantation.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 13; Dexamethasone; Doxorubicin; Female; Fever; Humans; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Remission Induction; Transplantation, Autologous; Vincristine

Acute renal failure (ARF) is a life-threatening complication after allogeneic stem cell transplantation (Allo-HSCT). Identification of ARF risk factors could be useful to develop preventive strategies for patients at high risk. The goal of this study was to evaluate the incidence and risk factors of ARF after reduced intensity conditioning Allo-HSCT (Allo-RIC). We included 188 consecutive patients who underwent Allo-RIC in our center between January 1999 and December 2006. ARF was defined as a decrease of at least 25% in baseline estimated glomerular filtration rate (GFR) calculated by modification of diet in renal disease (MDRD) equation. Conditioning consisted of fludarabine (Flu) 150 mg/m(2) in combination with busulfan (Bu) 8-10 mg/kg (n = 61), melphalan (Mel) 140 mg/m(2) (n = 115), cyclophosphamide (Cy) 120 mg/kg (n = 7) or low-dose total-body irradiation (TBI) 2 Gy (n = 5). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A (CsA) alone (n = 3) or in addition to methotrexate (MTX; n = 132) or mycophenolate mofetil (MMF; n = 51). The cumulative incidence of ARF at 1 year was 52% (n = 97 patients) after Allo-RIC. Most cases (86%) occurred within the first 3 months, and the main cause was the administration of CsA (71%). The risk factors associated with ARF in multivariate analysis were: administration of MTX (hazard ratio [HR] 1.9, P =.02), more than 3 lines of therapy prior to Allo-RIC (HR 1.8, P = .01), diabetes mellitus (HR 2.1, P < .01), and GVHD grade III-IV (HR 2.1, P = .015). In multivariate analysis, ARF was an independent risk factor for 1-year nonrelapse mortality (NRM) (HR 3, 95% confidence interval [CI]: 1.5-6, P = .002). Patients who experienced ARF had lower 1-year overall survival (OS; 53% versus 74%, P < .05). ARF is a frequent complication in patients after Allo-RIC, and it has a negative impact on outcome. Identification of ARF risk factors could help to avoid exposure to nephrotoxic drugs during the follow-up in patients at high risk.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cyclophosphamide; Cyclosporine; Female; Glomerular Filtration Rate; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Melphalan; Methotrexate; Middle Aged; Mycophenolic Acid; Premedication; Risk Factors; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation; Young Adult

Nonrelapse mortality (NRM) after reduced-intensity allogeneic transplants is likely to be influenced by abnormalities in renal function. We studied 141 patients diagnosed with acute myelogenous leukemia (AML) (n = 131) or high-risk myelodysplastic syndrome (MDS) (n = 10) who underwent allogeneic transplantation with fludarabine (Flu)/melphalan (Mel)-based regimens and hypothesized that moderate to mild renal function impairment increases NRM in this setting. Flu dose consisted of 25-30 mg/m(2) for 4 days and Mel dose was 100-180 mg/m(2). Donors were HLA-compatible siblings (n = 69) and matched unrelated donors (n = 72). Disease status at transplantation was complete remission (n = 56, 40%) or active disease (n = 85, 60%). The influence of the estimated glomerular filtration rate (GFR) measured before transplantation on outcomes was analyzed. GFR was estimated by both the Cockcroft-Gault (CG) and the modified diet in renal disease (MDRD) equations, using the creatinine value obtained prior to starting chemotherapy. Evaluated outcomes were overall survival (OS), NRM, and treatment-related mortality (TRM) at day 100 and 1-year posttransplantation. Median age was 55 years (range: 21-74 years); 59% of the patients were male. Estimated GFR by CG was > or =90 for 45 (32%), 60-89 for 78 (55%), and <60 for 18 (13%) patients. When estimated by MDRD, GFR was > or =90 for 65 (46%), 60-89 from 66 (47%), and <60 for 10 (7%) patients. The majority of patients by both estimations had a GFR between 60 and 89 (n = 78 by CG and n = 66 by MDRD) with no difference in the evaluated outcomes between this group and the subgroup of patients with a GFR <60 (P > .05). There were no differences in OS and NRM at day 100 and 1-year posttransplantation in the 3 groups by any GFR estimation method. In conclusion, a mild to moderate decrease in GFR was not associated with an increase in NRM.

Topics: Acute Kidney Injury; Adult; Aged; Glomerular Filtration Rate; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Myelodysplastic Syndromes; Remission Induction; Retrospective Studies; Transplantation Conditioning; Vidarabine; Young Adult

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

The treatment of AL amyloidosis was not successful until the advent of myeloablative chemotherapy consisting of high-dose intravenous melphalan followed by autologous peripheral blood stem cell transplantation. This new treatment has achieved better survival rates and, remarkably, it has obtained complete remission. Among patients with renal involvement, achievement of a complete hematological response was associated with a 50% reduction in proteinuria and stable creatinine clearance in more than 2/3 of patients. Despite of these excellent results, this new therapy is associated with significant toxicity, including the development of acute renal failure due to white blood cell lysis syndrome. We report a 59 year-old female with a nephrotic syndrome due to primary amyloidosis successfully treated autologous stem cell transplantation who developed acute renal failure caused by white blood cell lysis syndrome. The patient required treatment with granulocytic colony stimulating factor and intermittent hemofiltration and was discharged 23 days after melphalan administration with a satisfactory renal function and white blood cell count. After one year of follow up, she maintains a good glomerular filtration rate, a proteinuria of less than, 1 g/day and normal hematological values.

Topics: Acute Kidney Injury; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Melphalan; Middle Aged; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous; Tumor Lysis Syndrome

Patients with primary systemic amyloidosis (AL) have a poor prognosis. Median survival time from standard treatments is only 17 months. High-dose intravenous melphalan followed by peripheral blood stem cell transplant (PBSCT) appears to be the most promising therapy, but treatment mortality can be high. The authors have noted the development of acute renal insufficiency immediately after melphalan conditioning. This study was undertaken to further examine its risk factors and impact on posttransplant mortality.. Consecutive AL patients who underwent PBSCT were studied retrospectively. Acute renal insufficiency (ARI) after high-dose melphalan was defined by a minimum increase of 0.5 mg/dL (44 micromol/L) in the serum creatinine level that is greater than 50% of baseline immediately after conditioning. Urine sediment score was the sum of the individual types of sediment identified on urine microscopy.. Of the 80 patients studied, ARI developed in 18.8% of the patients after high-dose melphalan. Univariate analysis identified age, hypoalbuminemia, heavy proteinuria, diuretic use, and urine sediment score (>3) as risk factors. Age and urine sediment score remained independently significant risk factors in the multivariate analysis. Patients who had ARI after high-dose melphalan underwent dialysis more often (P = 0.007), and had a worse 1-year survival (P = 0.03).. The timing of renal injury strongly suggests melphalan as the causative agent. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. Development of ARI adversely affected the outcome after PBSCT. Effective preventive measures may help decrease the treatment mortality of PBSCT in AL patients.

Topics: Acute Kidney Injury; Adult; Aged; Amyloidosis; Drug Administration Schedule; Female; Humans; Male; Melphalan; Middle Aged; Retrospective Studies; Stem Cell Transplantation; Survival Rate

Topics: Acute Kidney Injury; Amyloidosis; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Kidney Function Tests; Melphalan; Middle Aged; Nephrotic Syndrome; Recovery of Function; Risk Assessment; Severity of Illness Index; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Purging; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Cyclophosphamide; Cystitis; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Infections; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Pilot Projects; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

To analyze causes of reversible and irreversible renal failure in myeloma patients, lethal outcomes, treatment policy.. 43 myeloma patients with renal failure entered the trial. The replacement therapy consisted of hemodialysis, hemofiltration, hemodiafiltration. All the patients received full-dose polychemotherapy according to the programs M-2 and VAD.. 69% of the patients retained normal renal function. 23% of the patients died. Partial recovery of renal function was observed in 1 patient who had to undergo dialysis once in 10-12 days. The patients survived from 5 days to 36 months (mean 20.6 months). The main causes of death in renal failure were sepsis (38%) and hemorrhagic stroke (14%).

Topics: Acute Kidney Injury; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Hemodiafiltration; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Peritoneal Dialysis; Prednisone; Renal Dialysis; Time Factors; Vincristine

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

Between June 1989 and June 1992, 12 patients with advanced multiple myeloma underwent peripheral blood stem cell autotransplantation after high-dose chemotherapy and radiotherapy. The conditioning regimen included melphalan (140 mg/m2), high-dose cyclophosphamide (120 mg/kg), methylprednisolone (2 g daily x 7), and total body irradiation (9-12 Gy). Transplant morbidity included severe mucositis (n = 7) and acute renal failure (n = 2) related to infusion of the stem cells. Engraftment was delayed (n = 4) in this heavily pretreated population, and two patients had complete graft failure. Despite the advanced nature and chemotherapy-refractory state of their disease, 11 of 11 evaluable patients achieved an objective response. Six patients survived to leave the hospital, and four remain alive--one died of acute leukemia induced by prior melphalan exposure. Three of the four are relapse-free at a median of 24.9 months (range, 18-28 months). Some patients with advanced refractory multiple myeloma can achieve objective responses from highdose chemoradiotherapy with peripheral blood stem cell rescue. Harvesting peripheral blood stem cells from high-risk patients early in their disease for later use may decrease the risk of graft failure. Peripheral blood stem cell transplantation after high-dose chemotherapy and total body irradiation can produce durable responses in patients with advanced refractory myeloma.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukapheresis; Male; Melphalan; Methylprednisolone; Middle Aged; Mucous Membrane; Multiple Myeloma; Pharyngitis; Recurrence; Whole-Body Irradiation

A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year-old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy.

Topics: Acute Kidney Injury; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Injections, Intravenous; Melphalan; Middle Aged; Multiple Myeloma; Oliguria; Renal Dialysis

Topics: Acute Kidney Injury; Humans; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisolone; Renal Dialysis; Waldenstrom Macroglobulinemia

Melphalan is widely used in the chemotherapeutic treatment of an ovarian cancer. Bone marrow depression, nail change, hypersensitivity, chronic pulmonary fibrosis, and nausea and vomiting, are the side effects reported as a result of the toxicity of Melphalan. So far as we know, renal toxicity caused by Melphalan has not been reported in the past literature. A case of acute renal failure induced by Melphalan in a patient with 3rd stage ovarian cancer is presented in this paper. This therefore is the first report of renal toxicity caused by Melphalan.

Topics: Acute Kidney Injury; Adenocarcinoma, Mucinous; Aged; Female; Humans; Kidney; Melphalan; Ovarian Neoplasms

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

Topics: Acute Kidney Injury; Adolescent; Humans; Male; Melphalan

Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.

Topics: Acute Kidney Injury; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Long-Term Care; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Procarbazine; Renal Dialysis; Time Factors; Vincristine

The technique of crossed immunoelectrophoresis (X-IEP) has been used to quantify free monoclonal light chains (LC) directly in the serum of patients with light chain disease, without preliminary gel or membrane filtration of serum to separate whole immunoglobulin. LC concentration is proportional to the area under an immunoprecipitin peak formed by LC in the patient's serum and an anti-LC antibody of appropriate specificity. Light chains of beta electrophoretic mobility can be processed in the standard X-IEP technique at pH 8.6. Light chains of gamma mobility must be processed in a modified technique using a pH of 5.0 and a carbamylated antiserum in the second dimension gel. Dose response curves obtained from the method in serial dilution experiments with sera from 18 patients gave correlation coefficients greater than or equal to 0.99. Replicate measurements of absolute LC concentration on the same specimens were within +/- 10%. The method can also detect polymerized light chains. Serum light chain levels were measured during the course of plasmapheresis therapy in three patients with light chain disease and renal failure. Light chain levels were shown to fall after plasmapheresis and to rise rather rapidly in the interval between treatments.

Topics: Acute Kidney Injury; Aged; Allopurinol; Calcitonin; Carmustine; Counterimmunoelectrophoresis; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Male; Melphalan; Paraproteinemias; Peritoneal Dialysis; Plasmapheresis; Prednisone; Vincristine

The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62% (P = 0.001). The lowest neutrophil counts following i.v. melphalan (1 mg/kg) averaged 4.9 x 10(3)/mm3 pre-nephrectomy and 0.9 x 10(3)/mm3 post-nephrectomy, respectively (P = 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 10(3)/mm3 in the pre-nephrectomized dogs, and 9.7 x 10(3/mm3 in those who had been nephrectomized (P = 0.002). Following nephrectomy, i.v. melphalan's terminal-phase plasma half-life and renal clearance were both raised (P = 0.02) to 75% over pre-nephrectomy values. These studies show that i.v. melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50% when used in myeloma patients with renal failure.

Topics: Acute Kidney Injury; Animals; Bone Marrow; Dogs; Kidney; Kinetics; Male; Melphalan; Metabolic Clearance Rate; Nephrectomy

A case of multiple myeloma with severe osteolytic destructions and myeloma kidney is presented, in whom a rapidly progressive renal insufficiency because of hyponatraemia and dehydration developed. After 5 months of regular dialysis treatment diuresis increased and a sufficient global kidney function recurred. Aetiological factors and the pathomechanisms of acute renal failure in multiple myeloma are discussed. We assume that acute renal insufficiency is - in rare cases - at least partly reversible. Therefore patients with acute renal failure and multiple myeloma should not be excluded from haemodialysis treatment because even complete rehabilitation can be achieved.

Topics: Acute Kidney Injury; Cyclophosphamide; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisolone; Renal Dialysis

Only four cases of immunoglobulin E (IgE) monoclonal "gammapathies" have been reported previously. Discussed here is a 57 year old man who presented with hypertension and the nephrotic syndrome. A monoclonal IgE-kappa component (0.6 mg/ml), which did not appear as an M spike on protein electrophoresis, was demonstrated by immunoelectrophoresis in the serum and urine. The patient's condition deteriorated rapidly due to renal failure, and he died five weeks after the diagnosis was made. Pathologic examination disclosed extensive glomerular lesions, but amyloid was not detected by light or electron microscopy. The possible relationship between the monoclonal gammapathy and kidney impairment is discussed.

Topics: Acute Kidney Injury; Fluorescent Antibody Technique; Humans; Hypergammaglobulinemia; Hypertension; Immunoglobulin E; Kidney; Male; Melphalan; Middle Aged; Prednisone

Topics: Acute Kidney Injury; Adult; Diuresis; Humans; Kidney Neoplasms; Male; Melphalan; Multiple Myeloma; Peritoneal Dialysis; Plasmapheresis

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

Our studies show that the malignant melanoma cell in human beings is more sensitive to the lethal effect of heat than its normal counterpart, the melanocyte. Malignant melanoma of the extremities presents unique problems; at times, local control can be extremely difficult. The addition of heat to regional perfusion with melphalan has dramatically improved the objective response of melanoma. Complications rise as the tempreature and duration of perfusion increase. These risks must be weighed carefully against the volume and extent of tumor. One hundred and eighty-five hyperthermic perfusions have been perfomed on 165 patients. When done with meticulous attention to details, this procedure is accompanied by minimal morbidity and mortality. Hyperthermic perfusion is currently the best treatment for recurrent melanoma of the extremities and has almost eliminated the necessity for amputation. Perfusion is recommended as a prophylactic measure for the more deeply invasive primary lesions. It reduces the incidence of regional recurrence. A retrospective statistical analysis of survival rates of patients treated with nonheated and heated perfusion for recurrent melanoma, State IIIA, was conducted. If the experience of the heated group continues, which from a clinical standpoint appears likely, then a striking advantage of heated perfusion over nonheated perfusion will be demonstrated. This superiority in survival rates for the heated group is now three to one or 300 per cent. The most reasonable explanation for the improvement in survival time of patients in State IIIA is stimulation of the immune response. As a result of our experience with heated perfusion of limbs, we are investigating the possibility that systemic hyperthermia may enhance the antitumor effects of various chemotherapeutic agents on melanoma.

Topics: Acute Kidney Injury; Age Factors; Aged; Cell Line; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Hot Temperature; Humans; Hyperthermia, Induced; Male; Melanocytes; Melanoma; Melphalan; Neoplasm Metastasis; Pulmonary Embolism; Recurrence; Sex Factors

Numerous plasma cells were transiently found in the urine of a patient with multiple myeloma. The patient was in acute renal failure, and she had K-type Bence-Jones proteinemia and proteinuria. A slide of stained urine sediment showed cells with freatures characteristic of plasma cells. Their cytoplasm was highly reactive with anti-K antiserum on immunofluorescence, suggesting that these were myeloma cells.

Topics: Acute Kidney Injury; Aged; Female; Humans; Hydrocortisone; Melphalan; Multiple Myeloma; Plasma Cells; Renal Dialysis; Urine

Two cases of acute renal failure complicating multiple myeloma are reported. In both, the renal failure preceded the diagnosis of multiple myeloma. In one case oliguria occurred after performance of a venogram; renal function returned to normal after two weeks of intermittent peritoneal dialysis, emphasizing the reversibility of the renal failure in some cases.

Topics: Acute Kidney Injury; Aged; Allopurinol; Female; Humans; Male; Melphalan; Multiple Myeloma; Peritoneal Dialysis; Prednisone; Radiography

Topics: Acute Kidney Injury; Aged; Bence Jones Protein; Blood Proteins; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Uremia

Topics: Acute Kidney Injury; Blood Proteins; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraplegia; Proteinuria; Renal Dialysis