melphalan and Kidney-Diseases

The monoclonal gammopathies of renal significance (MGRS) are a group of disorders characterized by monoclonal Ig deposition in the kidney, but are not associated with systemic lymphoma or overt multiple myeloma. The prevailing hypothesis is that the pathogenic paraproteins in MGRS are produced by underlying B cell or plasma cell clones. However, in the MGRS literature, the yield of detecting a clone has been variable, and progression to ESRD is common. Here, we present an "onco-nephrologic" approach to the MGRS disorders by highlighting recent advances in lymphoma and multiple myeloma that can be used in the evaluation and management of these patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Bortezomib; Cyclophosphamide; Dexamethasone; Humans; Immunoglobulins; Immunosuppressive Agents; Kidney Diseases; Lenalidomide; Melphalan; Oligopeptides; Paraproteinemias; Pentostatin; Rituximab; Thalidomide; Vidarabine

Various renal disorders are associated with monoclonal gammopathies, secondary to tissue deposition or precipitation of a monoclonal immunoglobulin (Ig) or a fragment thereof (isolated Ig light chain or heavy chain). They are classified according to the localization of renal lesions, either glomerular or tubular and to the pattern of ultrastructural organization of Ig deposits. Renal disease in monoclonal gammopathies may be isolated, or associated with various systemic symptoms particularly in AL amyloidosis, Randall-type monoclonal Ig deposition disease and monoclonal cryoglobulinemias. Except for myeloma cast nephropathy, which occurs in the setting of high-mass myeloma and is recognized after electrophoretic analysis of proteinuria and AL amyloidosis, which diagnosis is usually made after pathological examination of non-invasive tissue specimens (i.e. abdominal fat or minor salivary glands), a kidney biopsy is required to identify the other types of renal disorders associated with monoclonal gammopathies and to estimate renal prognosis. Renal pathological diagnosis is difficult and relies on careful examination of kidney biopsy samples, by light microscopy, immunofluorescence studies using conjugates specific for Ig light and heavy chains, IgG sub-classes and heavy chain constant domains and by electron microscopy. In some cases, additional studies are required to identify the nature of deposits, such as immuno-electron microscopy or mass spectrometric-based proteomic analysis after laser dissection. In patients with renal disorders related to Ig light chain precipitation or deposition (myeloma cast nephropathy, AL amyloidosis, Randall-type light chain deposition disease), measurement of serum free light chains at baseline and throughout follow-up is mandatory to evaluate clonal response to chemotherapy. A more than or equal to 50% decrease in serum free light chain levels is associated with increased renal and patient survival. In AL amyloidosis, serum levels of markers of cardiac disease (NT-proBNP and troponin) are also closely associated with prognosis. Efficient chemotherapy, tailored to the underlying plasma cell or lymphoproliferative disorder and adapted to renal function, should be promptly introduced, even in the absence of overt malignant haematological disease. Renal prognosis and patient survival (particularly in AL amyloidosis and cast nephropathy) are closely associated with the rapid achievement of an haematological response. The combi

Topics: Amyloidosis; Biopsy; Boronic Acids; Bortezomib; Dexamethasone; Heart Transplantation; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Kidney; Kidney Diseases; Kidney Transplantation; Melphalan; Paraproteinemias; Plasma Exchange; Pyrazines

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

During the past 10 to 15 years, there has been substantial progress in developing new treatments for the systemic amyloidoses. These advances have improved patient outcomes but have also raised new questions with direct clinical implications. For example, development of less intensive treatments for AL amyloidosis has made less certain the role of autologous stem cell transplantation, and new quantitative assays should now allow determination of the importance of fully eliminating amyloidogenic light chain production in AL disease. Additionally, observations from a clinical trial in AA amyloidosis have generated hypotheses about the relative contributions of amyloid precursors and mature fibrils to amyloidosis-associated kidney disease.

Topics: Amyloid; Amyloidosis; Humans; Kidney Diseases; Melphalan; Myeloablative Agonists; Stem Cell Transplantation; Transplantation, Autologous

We reviewed the literature in 2007 on 3 groups of systemic diseases affecting the kidney: lupic nephropathy (LN), small vessel vasculitis (SVV) and renal amyloidosis. A systematic review of 268 patients with LN pooled from 4 studies found that mycophenolic acid (MPA) in the induction phase caused more remissions and achieved greater renal survival than cyclophosphamide (CP), confirming it as a valid alternative to CP. Using a protocol including rituximab and MPA in the induction phase (14 days), MPA alone without corticoids is effective and safe in the maintenance phase. Rituximab has also been successfully used in CP-resistant forms of LN, where it reduces clinical activity and mesangial proliferation. Plasma exchanges achieve better results than bolus corticoids in SVS with severe renal failure. Complications are severe. Anti- TNF-alpha agents provide no benefit in this indication. Prolonged administration of low-dose corticoids reduces the incidence of relapses. MPA is an alternative to CP if this drug cannot be administered. Good results are achieved with rituximab in CP-resistant forms. According to a controlled trial, treatment of AL amyloidosis with dexamethasone and melphalan has equivalent results to highdose melphalan and rescue with hematopoietic stem cell transplant. In AA amyloidosis, eprosidate slows the rate of progression of renal failure.

Topics: Adrenal Cortex Hormones; Amyloidosis; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Combined Modality Therapy; Cyclophosphamide; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Failure, Chronic; Lupus Nephritis; Melphalan; Mycophenolic Acid; Plasma Exchange; Randomized Controlled Trials as Topic; Recurrence; Rituximab; Vasculitis

Renal involvement is common in multiple myeloma. Although several types of renal disease are observed, most of them are considered to be specifically related to monoclonal immunoglobulin light chains. Myeloma cast nephropathy is the most frequent and sometimes associated with acute renal failure. AL amyloidosis and monoclonal immunoglobulin deposit disease are often presented as a nephrotic syndrome. In this review, we describe the pathogenesis and diagnosis of these three renal diseases. We also focus on the treatment of renal disease in multiple myeloma, in the view points of the chemotherapy to reduce M-protein and the prevention to reduce the risks of promoting renal injury.

Topics: Amyloidosis; Biomarkers; Combined Modality Therapy; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Hypergammaglobulinemia; Immunoglobulin Light Chains; Kidney Diseases; Melphalan; Multiple Myeloma; Myeloma Proteins; Plasma Exchange; Prednisolone

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Humans; Immunoglobulin Light Chains; Kidney Diseases; Melphalan; Multiple Myeloma; Paraproteinemias; Stem Cell Transplantation

Between June 1991 and January 1995 we performed 67 peripheral blood progenitor cell transplants (PBPCT). Ten patients (group 1) were mobilised with 7 gm/m2 of cyclophosphamide followed by daily G-CSF injections (5 micrograms/kg, subcutaneously). When the white cell count reached 1 x 10(9)/1 they were leukapheresed for 5 days. After stem cell infusion they received G-CSF (10 micrograms/kg/day) until the neutrophil count reached 1.5 x 10(9)/1. Fifty-six patients had PBPCs mobilised with 3 gm/m2 of cyclophosphamide followed by daily subcutaneous G-CSF (5 micrograms/kg) and PBPCs were harvested on 2 consecutive days, when the white cell count rose to 4 x 10(9)/1. After stem cell infusion this group did not receive G-CSF. In 47 of the 56 patients (group 2) adequate MNC (> or = 4 x 10(8)/kg) and/or CFU-GM (> or = 10 x 10(4)/kg) were obtained. Insufficient MNC and/or CFU-GM were obtained in 10 patients. They were therefore transplanted using a combination of bone marrow and peripheral blood progenitor cells (group 3). Overall 64 patients successfully engrafted. Median days to neutrophils > or = 0.5 x 10(9)/1 were 9 (range 8-13), 12 (range 8-25) and 11 (range 9-16) and to platelets > or = 50 x 10(9)/1 were 11 (range 9-23), 13 (range 9-90) and 16 (range 13-99) in groups 1, 2 and 3 respectively. Patients in group 1 had a faster neutrophil recovery than patients in group 2 (P = 0.0002). The three patients who failed to engraft all received a combination of autologous peripheral blood and bone marrow cells.

Topics: Adolescent; Adult; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; Cell Movement; Colony-Forming Units Assay; Cyclophosphamide; Cytarabine; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Kidney Diseases; Leukapheresis; Leukocyte Count; Male; Melphalan; Middle Aged; Neoplasms; Podophyllotoxin; Retrospective Studies; Thiotepa; Transplantation Conditioning

Topics: Antineoplastic Agents; Drug Therapy, Combination; Humans; Hypercalcemia; Kidney Diseases; Melphalan; Multiple Myeloma; Myeloma Proteins; Pain; Prognosis

Topics: Amyloidosis; Arrhythmias, Cardiac; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney Diseases; Melphalan; Transplantation, Autologous

Treatment of mantle cell lymphoma (MCL) in younger patients remains a challenge. We report results of a phase 2 trial using cytarabine and rituximab as induction regimen before autologous stem cell transplantation. Patients younger than 66 years with stage 3 or 4 MCL were included. Treatment consisted of 3 courses of CHOP(21) with rituximab at the third one and 3 of R-DHAP. Responding patients were eligible for autologous stem cell transplantation with TAM6 or BEAM. Sixty patients were included. Median age was 57 years. Characteristics of patients were: BM involvement 85%, leukemic disease 48%, gastrointestinal involvement 52%, Performance Status > 16%, lactate dehydrogenase > 1N 38%, Mantle Cell Lymphoma International Prognostic Index (low 55%, intermediate 38%, high 13%). The overall response rate was 93% after (R)-CHOP and 95% after R-DHAP. Although uncommon after (R)-CHOP (12%), 57% of patients were in complete response after R-DHAP. With median follow-up of 67 months, median event-free survival is 83 months, and median overall survival is not reached. Five-year overall survival is 75%. Comparison with a previous study without rituximab shows improvement of outcome (median event-free survival, 51 vs 83 months). No toxic death or unexpected toxicities were observed. This study confirms that induction with rituximab and cytarabine-based regimens is safe and effective in MCL patients. This regimen is currently compared with R-CHOP(21) induction in a multicentric European protocol.

Topics: Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Kidney Diseases; Lymphoma, Mantle-Cell; Male; Melphalan; Middle Aged; Neoplasms, Second Primary; Peripheral Blood Stem Cell Transplantation; Prednisone; Rituximab; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine; Whole-Body Irradiation

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n=122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m(2) /d) and P (60 mg/m(2) /d) for 4d every 6 wk (n=62) or MP and thalidomide (100 mg/d) continuously (n=60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P=0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P=0.057). After 4 cycles of treatment (n=115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P=0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P=0.655; DFS 21.0 vs. 14.0 months, P=0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P=0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n=8, 14.0%) than in the MPT arm (n=2, 3.4%; P=0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P=0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cross-Over Studies; Female; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Opportunistic Infections; Prednisone; Survival Analysis; Thalidomide; Treatment Outcome

We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI (P = .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Female; Glomerular Filtration Rate; Humans; Induction Chemotherapy; Kidney Diseases; Maintenance Chemotherapy; Male; Melphalan; Multiple Myeloma; Neoadjuvant Therapy; Prednisone; Pyrazines; Survival Analysis; Thalidomide; Treatment Outcome

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach.

Topics: Adult; Aged; Amyloidosis; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Myeloablative Agonists; Remission Induction; Survival Rate; Transplantation, Autologous; Treatment Outcome

PURPOSE To assess bortezomib plus melphalan and prednisone (VMP) and melphalan and prednisone (MP) in previously untreated patients with multiple myeloma (MM) with renal impairment enrolled on the phase III VISTA study, and to evaluate renal impairment reversibility. PATIENTS AND METHODS Patients received nine 6-week cycles of VMP (bortezomib 1.3 mg/m(2), melphalan 9 mg/m(2), prednisone 60 mg/m(2)) or MP. Patients with serum creatinine higher than 2 mg/dL were excluded. Results In the VMP/MP arms, 6%/4%, 27%/30%, and 67%/66% of patients had baseline glomerular filtration rate (GFR) of < or = 30, 31 to 50, and higher than 50 mL/min, respectively. Response rates were higher and time to progression (TTP) and overall survival (OS) longer with VMP versus MP across renal cohorts. Response rates with VMP and TTP in both arms did not appear significantly different between patients with GFR < or = 50 or higher than 50 mL/min; OS appeared somewhat longer in patients with normal renal function in both arms. Renal impairment reversal (baseline GFR < 50 improving to > 60 mL/min) was seen in 49 (44%) of 111 patients receiving VMP versus 40 (34%) of 116 patients receiving MP. By multivariate analysis, younger age (< 75 years; P = .006) and less severe impairment (GFR > or = 30 mL/min; P = .027) were associated with higher reversal rates. In addition, treatment with VMP approached significance (P = .07). In both arms, rates of grade 4 and 5 adverse events (AEs) and serious AEs appeared higher in patients with renal impairment; with VMP, rates of discontinuations/bortezomib dose reductions due to AEs did not appear affected. CONCLUSION VMP is a feasible, active, and well-tolerated treatment option for previously untreated patients with MM with moderate renal impairment, resulting in 44% renal impairment reversal.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cohort Studies; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Melphalan; Multiple Myeloma; Multivariate Analysis; Prednisone; Prognosis; Pyrazines; Treatment Outcome

A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24-70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Leukapheresis; Male; Melphalan; Middle Aged; Prednisone; Survival Analysis; 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

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

Primary systemic amyloidosis is an uncommon disease characterized by the accumulation in vital organs of a fibrillar protein consisting of monoclonal light chains.. We treated 220 patients with biopsy-proved amyloidosis. The patients were randomly assigned to receive colchicine (72 patients), melphalan and prednisone (77), or melphalan, prednisone, and colchicine (71). They were stratified according to their chief clinical manifestations: renal disease (105 patients), cardiac involvement (46), peripheral neuropathy (19), or other (50).. The median duration of survival after randomization was 8.5 months in the colchicine group, 18 months in the group assigned to melphalan and prednisone, and 17 months in the group assigned to melphalan, prednisone, and colchicine (P<0.001). Among patients who had a reduction in serum or urine monoclonal protein at 12 months, the overall length of survival was 50 months, whereas among those without a reduction at 12 months, the overall length of survival was 36 months (P=0.03). Thirty-four patients (15 percent) survived for five years or longer.. Therapy with melphalan and prednisone results in objective responses and prolonged survival as compared with colchicine in patients with primary amyloidosis.

Topics: Aged; Amyloidosis; Antineoplastic Agents; Cardiomyopathies; Colchicine; Drug Therapy, Combination; Humans; Kidney Diseases; Melphalan; Middle Aged; Prednisone; Prospective Studies; Survival Analysis; Treatment Outcome

Between June 1991 and January 1995 we performed 67 peripheral blood progenitor cell transplants (PBPCT). Ten patients (group 1) were mobilised with 7 gm/m2 of cyclophosphamide followed by daily G-CSF injections (5 micrograms/kg, subcutaneously). When the white cell count reached 1 x 10(9)/1 they were leukapheresed for 5 days. After stem cell infusion they received G-CSF (10 micrograms/kg/day) until the neutrophil count reached 1.5 x 10(9)/1. Fifty-six patients had PBPCs mobilised with 3 gm/m2 of cyclophosphamide followed by daily subcutaneous G-CSF (5 micrograms/kg) and PBPCs were harvested on 2 consecutive days, when the white cell count rose to 4 x 10(9)/1. After stem cell infusion this group did not receive G-CSF. In 47 of the 56 patients (group 2) adequate MNC (> or = 4 x 10(8)/kg) and/or CFU-GM (> or = 10 x 10(4)/kg) were obtained. Insufficient MNC and/or CFU-GM were obtained in 10 patients. They were therefore transplanted using a combination of bone marrow and peripheral blood progenitor cells (group 3). Overall 64 patients successfully engrafted. Median days to neutrophils > or = 0.5 x 10(9)/1 were 9 (range 8-13), 12 (range 8-25) and 11 (range 9-16) and to platelets > or = 50 x 10(9)/1 were 11 (range 9-23), 13 (range 9-90) and 16 (range 13-99) in groups 1, 2 and 3 respectively. Patients in group 1 had a faster neutrophil recovery than patients in group 2 (P = 0.0002). The three patients who failed to engraft all received a combination of autologous peripheral blood and bone marrow cells.

Topics: Adolescent; Adult; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; Cell Movement; Colony-Forming Units Assay; Cyclophosphamide; Cytarabine; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Kidney Diseases; Leukapheresis; Leukocyte Count; Male; Melphalan; Middle Aged; Neoplasms; Podophyllotoxin; Retrospective Studies; Thiotepa; Transplantation Conditioning

The influence of renal insufficiency on melphalan-induced myelosuppression was examined during the initial 10 weeks of treatment in 295 patients with multiple myeloma. Patients were randomized to receive either oral melphalan (0.15 mg/kg/day for 7 days, followed by 0.05 mg/kg/day after recovery from the wbc count nadir) or iv melphalan (16 mg/m2 every 2 weeks for four doses, followed by a single dose every 4 weeks). All patients received a 6-week tapering course of prednisone. Patients with renal insufficiency (BUN greater than or equal to 30 mg/100 ml) had a significantly higher frequency of severe leukopenia (less than or equal to 1000 cells/mm3) following iv melphalan than did patients with normal renal function (50% vs 15%, respectively; P = 0.007). The latter effect resulted in an increased frequency of drug-related deaths secondary to infection. The frequency of severe thrombocytopenia (less than or equal to 25,000 cells/mm3) was also greater in patients with renal failure following iv melphalan therapy. Reduction of iv melphalan dose to 50% in patients with elevated BUN reduced the frequency of these complications to levels that were not significantly different from those observed in patients with normal renal function. The frequency of severe myelosuppression was independent of renal function in patients receiving oral melphalan. Possible explanations for these findings are discussed.

Topics: Blood Urea Nitrogen; Bone Marrow; Humans; Kidney; Kidney Diseases; Leukopenia; Melphalan; Multiple Myeloma; Random Allocation; Thrombocytopenia

Three hundred and seventy-two patients were randomized between 3 regimens of chemotherapy: cyclophosphamide, intermittent melphalan, and melphalan with prednisone, and were followed up to death or for at least 5 years. There was no difference in survival between the treatments, either overall or in any subgroup of patients. Therefore, the choice among these 3 treatments should be guided by the patient's comfort and convenience. The most important prognostic feature at presentation was the quality of renal function. It was possible to define good, intermediate and poor renal-function groups which were highly correlated with prognosis (X2 for trend = 62.6). The haemoglobin level at presentation was strongly correlated with prognosis among patients in the good renal-function group. Among 107 patients who presented with good renal function and with haemoglobin above 100 g/l, the 5-year survival was 43%. Other prognostic features were much less important when account was taken of renal function and haemoglobin level.

Topics: Aged; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Follow-Up Studies; Hemoglobinometry; Humans; Immunoglobulin M; Kidney Diseases; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Prognosis; Proteinuria; Urea

At present, a diverse array of treatment regimens are available for systemic amyloid light-chain (AL) amyloidosis. Both cyclophosphamide + thalidomide + dexamethasone (CTD) and melphalan + dexamethasone (MD) regimens have been recommended as first-line therapies, but no detailed comparative studies of the two have been performed. This study is the first to compare the efficacy and tolerability of the CTD and MD regimens in the treatment of AL amyloidosis.. We retrospectively reviewed data from consecutive patients with AL amyloidosis who were treated with MD or CTD as the initial regimen between June 2012 and January 2018.. In the final analysis, 38 patients received CTD, and 30 received MD. There were no significant differences in baseline characteristics, including age, sex, renal function, involved organs, level of free light chains, and Mayo Clinic amyloidosis prognostic staging. The overall hematologic response rates in the CTD and MD groups were 69.0% versus 68.0%, respectively (P = 0.94), including a complete response in 27.6% versus 8.0% (P = 0.14). Neither group reached the estimated median overall survival, and the difference between the 2 groups was not significant (P = 0.17). The median progression-free survival times were 36 versus 14 months (P = 0.24) in the CTD and MD groups, respectively. The CTD group achieved a numerically but not statistically higher prevalence of kidney response (52.9% vs 37.0%; P = 0.22). The most common adverse events in the 2 treatment groups were fatigue (48.5% vs 21.7%; P = 0.04) and constipation, anemia, nausea/vomiting, neutropenia, and syncope (all, P = NS). Deaths occurred in 6 patients in the CTD group and 9 patients in the MD group; none were considered by the investigators as related to the study treatments. There were no other serious adverse events observed in our study.. The CTD regimen may not be inferior to standard oral MD in terms of overall hematologic response and overall survival. Although this study was of retrospective and negative-control design with some additional limitations, it may provide a therapeutic option for use in developing countries where patients cannot afford bortezomib or melphalan.

Topics: China; Cyclophosphamide; Dexamethasone; Humans; Immunoglobulin Light-chain Amyloidosis; Immunosuppressive Agents; Kidney Diseases; Melphalan; Retrospective Studies; Thalidomide

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23-68 years). Median time from diagnosis to transplant was 7 months (3-79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9-144.7 months) and 73.8 months (95% C.I. 57.7-89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p = 0.024), while OS was better with CR/VGPR post-ASCT (p < 0.001) and lenalidomide maintenance therapy (p = 0.009). PFS was affected by CR/VGPR pre-ASCT (p = 0.021), CR/VGPR post-ASCT (p < 0.001), and transplant in first remission (p = 0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p = 0.007) and CR/VGPR response post-ASCT (p = 0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p = 0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p = 0.073).. Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Prognosis; Proportional Hazards Models; Remission Induction; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

We report our retrospective analysis of 40 patients who received high-dose melphalan and autologous stem cell transplantation for systemic immunoglobulin light-chain (AL) amyloidosis. Between 2006 and 2013, 40 patients with AL amyloidosis were transplanted at our medical center. Their median age was 54 years (range 32-70 years): 18 were male. The dominant organs involved were the heart in 13 patients, and kidney in 22: and other organs were involved in five. The median melphalan dose administered was 129 (range 50-200) mg/m(2), and the median infused CD34(+) cells was 2.69 (range 1.17-11.26) × 10(6)/kg. Of the 40 patients, 30 are alive after a median follow-up of 42 (range 12-94) months, and the 4-year estimated overall survival rate was 74% (95% CI 56-86%). Four patients died ≤ 100 days post-ASCT (heart failure in three patients, bacteremia in one). The 4-year estimated survival of the patients with cardiac involvement was 54%, significantly lower than that of the other patients (91%). Hematological and organ responses were 52 and 50%, respectively. Careful patient selection and experienced management are important, especially for patients with cardiac involvement. It is also important to develop additional treatment for patients who do not achieve a hematological and/or organ response.

Topics: Adult; Aged; Amyloidosis; Cardiomyopathies; Cohort Studies; Female; Follow-Up Studies; Humans; Immunoglobulin Light Chains; Kidney Diseases; Male; Melphalan; Middle Aged; Retrospective Studies; Stem Cell Transplantation; Survival Rate; Transplantation, Autologous; Treatment Outcome

The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ(2) or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Child; Child, Preschool; Cohort Studies; Etoposide; Female; Hepatic Veno-Occlusive Disease; Humans; Hypertension, Pulmonary; Infant; Kidney Diseases; Male; Melphalan; Mucositis; Myeloablative Agonists; Neuroblastoma; Pancytopenia; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Young Adult

High-dose melphalan with stem cell transplantation (HDM/SCT) extends survival and induces hematologic and clinical responses in patients with light chain (AL) amyloidosis. Eighty percent of melphalan is bound to plasma proteins (60% albumin-bound). We hypothesized that patients with profound hypoalbuminemia have a greater free melphalan fraction and more toxicity. Patients with AL amyloidosis treated with HDM/SCT between 2011 and 2014 with severe hypoalbuminemia (SH), defined as serum albumin ⩽2 g/dL were studied retrospectively. Sixteen patients with SH were identified. Forty-one patients without severe hypoalbuminemia (WSH) treated between 2011 and 2012 served as control. The incidence of acute renal failure requiring hemodialysis was 25% among patients with SH, compared with 5% among patients WSH (P=0.05). Not all patients who needed dialysis required it long term; 6.25% for SH and 2.44% for WSH (P=0.49). The rates of grade 3 or 4 febrile neutropenia and gastrointestinal toxicities were not significantly different between the groups. Engraftment kinetics were similar for both groups. Grade 4 renal toxicity and grade 3 lightheadedness were more frequent in patients with SH undergoing HDM/SCT for AL amyloidosis. Further studies into the mechanism of increased renal toxicity in patients with SH are warranted.

Topics: Case-Control Studies; Female; Hematopoietic Stem Cell Transplantation; Humans; Hypoalbuminemia; Immunoglobulin Light-chain Amyloidosis; Kidney Diseases; Male; Melphalan; Middle Aged; Renal Dialysis; Retrospective Studies; Transplantation, Autologous

To investigate the clinical characteristics and histopathological features of kidney disease in elderly patients.. We retrospectively analyzed the results of 4,185 consecutive renal biopsies, and 288 patients aged >60 years at the Second Hospital of Jilin University from January 1998 to December 2013 were finally included. All patients had been clinically and histologically diagnosed with kidney disease.. Nephrotic syndrome was the main clinical indication for biopsy. Twenty-four patients (8.33 %) experienced a minor complication related to their biopsy procedure. Among patients diagnosed as primary glomerulonephritis (GN), membranous nephropathy (MN) was the most frequent subclassification (24.7 %), followed by mesangioproliferative glomerulonephritis (MsPGN, 11.1 %) and IgA nephropathy (IgAN, 8.0 %). Amyloidosis (8.7 %) was the most common secondary GN, followed by antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune GN (5.2 %) and diabetic nephropathy (DN, 3.8 %). Based on renal biopsies results, 143/288 patients received immunosuppressive therapy and showed an overall remission rate (complete plus partial remissions) of 74.1 %. Among 71 MN patients, 29 patients received steroids plus cyclophosphamide and showed a remission rate of 79.3 %, while 42 patients received steroids and tacrolimus and showed a remission rate of 90.5 %. Among 25 patients with amyloidosis, 22 cases received melphalan plus dexamethasone and showed a remission rate of 40.9 %, while three patients received vincristine, adriamycin, and dexamethasone and showed a remission rate of 66.7 %.. Making an accurate pathologic diagnosis by renal biopsy is crucial for selecting the proper treatment for elderly patients with kidney disease.

Topics: Aged; Aged, 80 and over; Amyloidosis; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antineoplastic Agents, Alkylating; Autoimmune Diseases; Biopsy; Cyclophosphamide; Dexamethasone; Diabetic Nephropathies; Female; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Retrospective Studies; Tacrolimus; Treatment Outcome

High-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) for light chain amyloidosis (AL) was performed in 31 patients at Oregon Health and Science University between 2005 and 2012. Fifteen patients had cardiac involvement.. Patients received melphalan 200 mg/m(2) or dose-adjusted HDM (100-140 mg/m(2)) depending on high risk features. Thirteen patients proceeded directly to ASCT after diagnosis, 12 patients received a bortezomib-containing regimen, and 6 received a variety of other induction regimens.. The day 100 treatment-related mortality was 9.6%. Overall hematologic (ORR) and organ response rates (OR) in the whole cohort after ASCT were 77% and 58%. ORR and OR in the bortezomib pretreated group were 92% and 75% vs. 69% and 54% in the group that received no pretreatment. The median time to maximum hematologic response after ASCT was reduced in the group that received bortezomib induction (3 vs. 14 months). Overall cardiac response rate was 60%; 100% in patients pretreated with bortezomib and 43% in those without induction treatment. With a median follow-up of 2.9 years, the 3-year progression-free and overall survival rates in the entire cohort were 66% and 73% and in those with cardiac involvement, 73% and 80%.. We observed that bortezomib-based induction is well tolerated in patients with and without cardiac involvement and suggest that this approach be studied in prospective multi-institutional trials.

Topics: Adult; Aged; Amyloidogenic Proteins; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cardiomyopathies; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Kaplan-Meier Estimate; Kidney Diseases; Lenalidomide; Male; Melphalan; Middle Aged; Myeloablative Agonists; Proteasome Inhibitors; Pyrazines; Remission Induction; Retrospective Studies; Thalidomide; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

A 62-year-old female patient was admitted to our hospital for evaluation of nephrotic syndrome. Monoclonal gammopathy (IgG λ type) and urinary Bence Jones proteins were detected in the serum and urine by the immunofixation method. The initial renal biopsy revealed amyloid deposition in mesangial area, glomerular capillary walls and arterioles by Congo-red staining, and amyloid fibers were detected by electron microscopy. On the bone marrow test, plasma cells accounted for 8.6%. Based on these findings, we diagnosed as AL amyloidosis associated with multiple myeloma. We treated her by high-dose intravenous injection therapy of melphalan combined with autologous peripheral blood stem cell transplantation. She achieved complete hematologic response 27 months later, however. Urine M-protein disappeared 2 months after treatment, and proteinuria slowly disappeared 17 months after treatment. On the other hand, amyloid fibers remained in renal biopsied tissues at 17 and 53 months after therapy. Electron microscopic examination also revealed the similar amyloid fibers in glomeruli. These findings suggest that, in this case, immunoglobulin light chains may cause directly and/or indirectly glomerular epithelial injury and nephrotic range proteinuria rather than via amyloid fiber formation.

Topics: Amyloidosis; Combined Modality Therapy; Female; Humans; Kidney Diseases; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous

Topics: Amines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Boronic Acids; Bortezomib; Combined Modality Therapy; Creatine Kinase, MM Form; Cyclohexanecarboxylic Acids; Dexamethasone; Drug Synergism; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunologic Factors; Kidney Diseases; Lenalidomide; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Polyneuropathies; Pravastatin; Pyrazines; Rhabdomyolysis; Thalidomide

Renal impairment (RI) is a severe complication throughout the course of multiple myeloma (MM). Bortezomib has been shown to be highly active in MM patients with RI. We designed this retrospective analysis to investigate the safety and efficacy of bortezomib-based therapy in 117 MM patients with RI, 14 cases required dialysis. A total of 603 cycles of bortezomib were administered (median number, five cycles/patient). Ten patients required early discontinuation of bortezomib because of WHO grade IV toxicity. The rate of bortezomib discontinuation in cases with severe, moderate and mild RI was 11%, 5% and 0%, respectively (P = NS). Overall, 91 episodes of WHO grade III/IV toxicity were observed. At least a partial response was documented in 83/113 evaluable patients (73%), including complete response (19%) and near complete response (8%). The overall response rate was similar across RI subgroups. Reversal of RI was documented in 41% of patients after a median of 2.3 months (range 0.4-7.9). In three of 14 patients on dialysis, renal replacement therapy was discontinued after 1, 1 and 4 months. The 2-yr estimate of response duration and overall survival was 70% and 51%, respectively. In conclusion, bortezomib-based regimens are safe and effective and should be considered as appropriate treatment options for MM patients with any degree of RI.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cardiovascular Diseases; Clinical Trials as Topic; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; Gastrointestinal Diseases; Glomerular Filtration Rate; Hematologic Diseases; Humans; Italy; Kidney Diseases; Male; Melphalan; Middle Aged; Multicenter Studies as Topic; Multiple Myeloma; Neoplasm Proteins; Peripheral Nervous System Diseases; Protease Inhibitors; Proteasome Inhibitors; Pyrazines; Retrospective Studies; Survival Analysis; Thalidomide

Quantitative assay for serum free light chains (sFLC) is reported as a useful test for diagnosis and monitoring of patients with nonsecretory multiple myeloma (NSM). We performed serial sFLC assays in a patient with NSM with light chain cast nephropathy (LCCN) and light chain deposition disease (LCDD). After 3 cycles of VAD induction therapy, while plasma cells in the marrow decreased from 93.0% to 0.2%, sFLCkappa/lambda ratio remained abnormal. Flow cytometry assay also showed that these plasma cells were CD19 negative. After the subsequent high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation (PBSCT), the sFLCkappa/lambda ratio returned to normal and the patient achieved a stringent complete response (sCR). One year after PBSCT, the patient remained in sCR with improved renal function. The quantitative FLC assay was useful for the diagnosis and monitoring of NSM and LCDD in this patient.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Dexamethasone; Doxorubicin; Female; Humans; Immunoassay; Immunoglobulin Light Chains; Kidney Diseases; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Reagent Kits, Diagnostic; Vincristine

Treatment-related mortality (TRM) is not uncommon in patients after the first course of vincristine-doxorubicin-dexamethasone (VAD) chemotherapy,but quite rare after melphalan-prednisolone (MP). This motivated us to compare the rates of TRM after the first course of VAD with those after the first course of MP. We retrospectively assessed survival and TRM in 179 patients treated for multiple myeloma with either MP or VAD. Survival was similar in two groups (P 50.463 in log-rank test). However, TRM was significantly higher inpatients after the first course of VAD (11 in 100 patients, 11.0%) than that after the first course of MP (1 in 79, 1.3%; P 5 0.010). Poor performance status (P 5 0.004) and advanced age (P 5 0.009) before treatment were independent significant factors associated with TRM after the first course of induction therapy. Pyogenic infection was the major cause of TRM after VAD (9 in 11, 81.8%). We concluded that VAD should be cautiously used as induction therapy in multiple myeloma patients, especially in elderly and/or those with poor performance status.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Infections; Kidney; Kidney Diseases; Male; Melphalan; Multiple Myeloma; Neoplasm Staging; Prednisone; Retrospective Studies; Survival Analysis; Vincristine

Comorbidity factors have been reported in cancer patients to predict progression free survival (PFS) and overall survival (OS). Renal impairment (RI) is postulated as one negative prognostic factor in multiple myeloma (MM). The study aim was to detect the best way to define RI and the impact of different RI stages on MM outcome.. In this multicenter analysis, we determined RI [serum creatinine, estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) and Cockcroft-Gault] and other prognostic factors in 198 MM patients to ascertain their value on PFS and OS.. Median serum creatinine was 0.9 mg/dL in all patients, whereas the eGFR - being decreased with a median of 80 mL/min/1.73 m(2)- allowed to detect early stages of RI. Via univariate analysis, we observed increasing hazard ratios (HRs) for impaired OS with deteriorating eGFR: with eGFR(MDRD)<90 and <30, HRs were 1.3 and 2.9, respectively. Multivariate analysis determined RI with eGFR<30 and <50 as well as age >59 yr as most important variables for OS. By incorporating eGFR<30 as the most relevant factor determined via multivariate analysis and beta(2)-microglobulin (beta(2)-MG) in a novel MM-risk score, we identified patients with significantly differing OS: median survival with 0, 1 or 2 risk factors were 71, 48, and 24 months, respectively.. These findings demonstrate that RI is frequent in MM, best detected via eGFR determination and an important prognostic factor. eGFR in combination with beta(2)-MG allows definitive risk stratification with largely differing survival in MM.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Combined Modality Therapy; Comorbidity; Creatinine; Dexamethasone; Doxorubicin; Female; Glomerular Filtration Rate; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Prednisone; Prognosis; Retrospective Studies; Risk Assessment; Thalidomide; Treatment Outcome; Vincristine

Topics: Amyloidosis; Combined Modality Therapy; Female; Humans; Kidney Diseases; Melphalan; Middle Aged; Stem Cell Transplantation

No established treatments for systemic AL amyloidosis have been determined, and only four reports have described allogeneic stem cell transplantation for this disease. We report the case of a patient with orthostatic hypotension, diarrhea, nephrotic syndrome, and cardiac amyloidosis due to systemic AL amyloidosis. Reduced intensity allogeneic stem cell transplantation (RIST) was performed using a conditioning regimen comprising fludarabine 125 mg/m2 and melphalan 90 mg/m2. Hematologically complete remission and symptomatic improvement were obtained without severe transplantation-related complications. RIST may thus offer a useful treatment strategy for systemic AL amyloidosis complicated by cardiac amyloidosis.

Topics: Adult; Amyloidosis; Diarrhea; Drug Therapy, Combination; Heart Diseases; Humans; Hypotension; Japan; Kidney Diseases; Male; Melphalan; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Remission Induction; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

POEMS syndrome is a rare plasma cell disorder, characterized by polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein, and skin lesions. Although not included in the acronym, renal lesions also are characteristic of this disease and sometimes require dialysis therapy. We treated a 61-year-old woman with POEMS syndrome with high-dose melphalan therapy (HDT) supported by autologous blood stem cell transplantation (SCT), and clinical remission was achieved. A repeated renal biopsy showed the striking effectiveness of this therapy on renal lesions. Pathological features of the renal lesions, such as membranoproliferative glomerulonephritis-like lesions, microangiopathic glomerulopathy, and mesangiolytic lesions with microcapillaries, almost completely disappeared. This treatment also markedly decreased serum levels of vascular endothelial growth factor (VEGF). These findings indicate that HDT with SCT is effective, even on renal lesions in patients with POEMS syndrome, and suggest that high serum VEGF concentrations are associated closely with the development of renal lesions in patients with this type of plasma cell disorder.

Topics: Combined Modality Therapy; Female; Humans; Kidney Diseases; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; POEMS Syndrome; Remission Induction; Severity of Illness Index

Light chain deposition disease (LCDD) is caused by a clonal plasma cell disorder in which fragments of monoclonal immunoglobulin light chains form non-fibrillary deposits in various tissues resulting in organ dysfunction. Crystal storing histiocytosis (CSH) is another light chain deposition disorder in which monoclonal light chains form intracytoplasmic crystals. Both are uncommon diseases for which there is limited treatment experience. Between 2003 and 2005, five patients with LCDD and one with CSH were treated at Boston University Medical Center with high-dose melphalan and autologous peripheral blood stem cell transplantation (HDM/SCT). Five of the six patients had predominantly renal involvement, and one patient with LCDD had biopsy-proven deposits in the myocardium. Molecular characterization revealed that the pathologic light chains were kappa in four of the six patients, and sequence analysis revealed unusual germline donor genes and high rates of amino-acid substitutions. One light chain sequence encoded a new potential N-linked glycosylation site, and another showed evidence of antigen selection. All patients are alive and five of the six patients are in complete hematologic remission at a median follow-up of 12 months (range 4-29 months) after HDM/SCT. In our experience, HDM/SCT is a feasible and effective treatment approach for these disorders.

Topics: Adult; Histiocytosis; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Kidney Diseases; Male; Melphalan; Middle Aged; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Cardiac involvement occurs in up to 50% of patients with primary or A amyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic peptide (BNP) has been proposed as a guide for treatment of heart failure patients and as an index of myocardial dysfunction in patients with ALA. Data about BNP dosage for cardiovascular monitoring of patients with ALA on renal replacement therapy are lacking.. A 64 year old Caucasian man was admitted because of nephrotic syndrome in July 2003. Renal diagnosis was ALA. Melphalan and prednisolone were given but renal function worsened and in April 2004 standard bicarbonate hemodialysis was started. In March 2004 thalidomide was added to his therapy. During the follow-up ejection fraction was stable and was 65% on the contrary E/A ratio gradually increased and overtook 1. BNP plasma levels were increased and the values recorded during the follow-up were: 2505 pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005. In September 2005 BNP was 3380 pg/mL. The patient was still alive after a follow-up longer than two years.. In ALA patients a powerful prognostic role of BNP has been reported whose expression is increased in ventricular myocytes of patients with cardiac involvement. BNP level monitoring does not appear to be superior to standard echocardiography in evaluating cardiovascular status of uremic patients with ALA.

Topics: Amyloidosis; Anti-Inflammatory Agents; Bicarbonates; Buffers; Cardiac Output, Low; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Nephrotic Syndrome; Prednisolone; Renal Dialysis; Thalidomide; Treatment Outcome

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Drug Combinations; Female; Glucose Oxidase; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Kidney Diseases; Lactoperoxidase; Male; Melphalan; Middle Aged; Models, Theoretical; Multiple Myeloma; Muramidase; Myeloablative Agonists; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

To analyse the pharmacokinetics of melphalan in 52 children (0.3-18 years) and determine whether any clinical factors affect the pharmacokinetic parameters Additionally, to examine whether a test melphalan dose can predict the pharmacokinetics of a full dose, when there are 5 intervening days of carboplatin therapy.. Melphalan concentrations were measured in 14 blood samples collected from each child following doses ranging from 30 to 180 mg m(-2). The pharmacokinetics were analysed with Kinetica 4.0.. Children who did not have carboplatin (n = 27) had median melphalan clearance (CL) of 15.5 l h(-1) m(-2) (interquartile range: 12.4-19.9 l h(-1) m(-2)) and steady state volume of distribution (Vss) of 14.9 l m(-2) (interquartile range: 12.7-18.3 l m(-2)). Children who had carboplatin (n = 25) had 34% lower median CL (10.2 l h(-1) m(-2)) and 18% lower median Vss (12.2 l m(-2)) (P < 0.001). Melphalan elimination was impaired in a separate group of three children given concomitant carboplatin and etoposide. Stepwise multiple linear regression indicated that weight, carboplatin, glomerular filtration rate (GFR) and total body irradiation (TBI) significantly affected CL, while weight and carboplatin influenced Vss. A test dose (10 mg m(-2)) tended to underpredict the area-under-the-concentration-vs.-time-curve for a full (180 mg m(-2)) dose in 19 individuals given carboplatin.. In children, melphalan CL is influenced by weight, carboplatin, TBI and GFR. Vss is influenced by weight and carboplatin.

Topics: Adolescent; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Area Under Curve; Body Weight; Bone Marrow Transplantation; Carboplatin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Interactions; Glomerular Filtration Rate; Humans; Infant; Kidney Diseases; Melphalan; Neoplasms; Time Factors; Whole-Body Irradiation

We here report a case of a 50-year-old man who showed histologically evident resolution of primary amyloidosis by melphalan and prednisolone. The patient was admitted to our hospital for further evaluation of nephrotic syndrome and remarkable hepatomegaly with refractory ascites, on September 11, 1998. Laboratory tests at presentation showed nephrotic syndrome with slight renal impairment and elevation of the enzymes of the biliary system. Monoclonal light chains were not detected in the serum or urine by immunoelectrophoresis. A renal biopsy revealed global deposition of amyloid in all glomeruli, interstitium and blood vessels. Immunofluorescence staining was positive for kappa light chains. Liver biopsy specimens showed extensive deposition of amyloid along sinusoid walls. Bone marrow aspiration contained 7% plasma cells but no clusters or abnormal cells. Based on these findings, systemic AL- (amyloid light chain) amyloidosis was diagnosed, and the treatment with combinations of melphalan and prednisolone was started from October 1998 at intervals of 4-6 weeks. Renal impairment progressed, resulting in the initiation of maintenance hemodialysis in February 1999. Reinfusion of ascitic fluid into the hemodialysis circuit had been performed from March 1999 for refractory ascites, and ascites disappeared in July 1999. Furthermore, urinary output increased after 14 courses of chemotherapy. Renal function gradually ameliorated with a concomitant reduction in the enzymes of biliary system, and finally hemodialysis was discontinued in April 2001. Sixteen courses of chemotherapy were administered by April 2001. Proteinuria was negative in August 2001. A second renal biopsy was performed on November 20, 2001, which showed markedly decreased amyloid deposition and a proliferation of mesangial cells and increase in matrix in various degrees. We report a case of a patient with primary amyloidosis who was successfully treated by melphalan and prednisolone, resulting in marked resolution of renal amyloidosis.

Topics: Alkylating Agents; Amyloidosis; Drug Therapy, Combination; Glucocorticoids; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Prednisolone; Treatment Outcome

High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown.. In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow.. In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy.. Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.

Topics: Amyloid; Amyloidosis; Antineoplastic Agents, Alkylating; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Paraproteinemias; Remission Induction; Transplantation, Autologous

Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. From April 1992 to December 1998, 23 evaluable patients received HDC within the German Cooperative Wilms Tumor Studies. Nineteen were given melphalan, etoposide and carboplatin (MEC); the others received different regimens. The dose of carboplatin was adjusted according to renal function. Indications for HDC were high-risk relapse in 20 patients, bone metastases in two patients and no response in one patient. Fourteen of 23 patients are alive after a median observation time of 41 months, 11 of 14 in continuous complete remission, three in CR after relapse post HDC. The estimated survival and event-free survival for these patients are 60.9% and 48.2%. Twelve children relapsed after HDC; nine of them died within 12 months and three are surviving from 20 to 33 months after relapse. The main toxicities were hematologic, mucositis and renal (tubular dysfunction; intermittent hemodialysis in one patient). There were no toxic deaths. About half of the children suffering from Wilms tumor with very unfavorable prognostic factors survive disease-free after HDC for over 3 years. Besides hematological toxicity, mucositis and infections, renal function is at risk during HDC. With dose adjustment on glomerular filtration rate, however, no permanent renal failure was observed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Etoposide; Female; Germany; Hematologic Diseases; Humans; Ifosfamide; Infant; Kidney Diseases; Kidney Neoplasms; Life Tables; Lung Neoplasms; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; Prognosis; Stomatitis; Survival Analysis; Thiotepa; Transplantation, Autologous; Wilms Tumor

Despite significant efficacy of melphalan and prednisone in the therapy of systemic AL(light chain amyloid)amyloidosis the prognosis of the disease is poor. In patients with severe renal manifestation the reported results of low-dose melphalan therapy are inconclusive with respect to relief of clinical symptoms and overall prognosis.. We report our results of therapy in a group of 22 patients (8 women, 14 men, mean age 60 years) with renal involvement as the main manifestation of systemic AL-amyloidosis without overt myeloma.. Ten patients were treated with low doses of melphalan and prednisone. No significant clinical improvement was observed in any case: the patients died an average of 12 months after diagnosis of the disease. Three patients were treated with high doses of melphalan followed by autologous stem cell transplantation. One patient died due to septicaemia after high-dose chemotherapy. Two of the patients experienced significant remission and live virtually free of clinical symptoms 12 and 18 months after therapy. Nine patients were treated only symptomatically: four of them were alive an average of 30 months after diagnosis of systemic AL-amyloidosis.. Only high-dose melphalan therapy offered a realistic chance of amelioration of clinical symptoms in our group of patients, although therapy-associated risks seem to be high. In patients with severe renal amyloidosis, who are not considered for high-dose therapy, particularly careful consideration of potential benefits and possible risks of conventional melphalan therapy is necessary, because the results of this approach are in doubt.

Topics: Adult; Aged; Amyloidosis; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Prednisone; Risk Factors; Time Factors; Transplantation, Autologous

Carboplatin and melphalan are two drugs whose toxicity profile makes them suitable for use in high doses followed by stem cell rescue. We report the use of high-dose carboplatin, with the dose based on glomerular filtration rate (GFR), combined with melphalan followed by autologous stem cell rescue in children with advanced stage or chemoresistant solid tumours. Thirty children were treated. After multiagent induction chemotherapy before BMT, 13 were in CR, five in VGPR, 11 in PR and one had progressive disease. They received melphalan, 180 mg/m2 and carboplatin, followed by autologous stem cell rescue. The dose of carboplatin was varied by GFR rather than fixed by surface area. The dose given ranged from 0.7 to 2.6 g/m2. Haematological and gastrointestinal toxicities were severe. Life-threatening or fatal toxicity was attributable to opportunistic infection in two cases and regimen-related in two cases. Of the 30 patients, 15 are alive and 13 disease-free at 4-36 months post-BMT. This simple two-drug combination has been used as consolidation of initial remission for patients with high-risk tumours. The toxicity is severe but tolerable. Use of a carboplatin dose based on GFR should optimise effectiveness in patients with good renal function and avoid excessive toxicity where renal function is impaired.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Carboplatin; Child; Child, Preschool; Disease-Free Survival; Female; Glomerular Filtration Rate; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infections; Kidney Diseases; Male; Melphalan; Neoplasms; Neuroblastoma; Treatment Outcome

Topics: Combined Modality Therapy; Cyclophosphamide; Humans; Kidney; Kidney Diseases; Melphalan; Multiple Myeloma; Plasmapheresis; Prednisolone

Nineteen patients with light-chain deposition disease (LCDD) were studied retrospectively. This report presents data on long-term patient and renal survival and the response to intermittent administration of melphalan and prednisone. Immunoelectrophoresis or immunofixation demonstrated a monoclonal protein in the serum of 78% and in the urine of 84% of the patients; 16% had no demonstrable monoclonal protein in serum or urine. The median age at presentation was 51 years (range, 37 to 77 years). Twelve (63%) of the patients had a monoclonal protein of undetermined significance without evidence of myeloma. The typical glomerular lesion was a diffuse mesangial nodular lesion that was positive for periodic acid-Schiff (PAS) stain with acute and chronic tubulointerstitial changes. Fifteen patients had kappa light-chain deposition and four had lambda light-chain deposition. Five-year actuarial patient survival and survival free of end-stage renal disease were 70% and 37%, respectively. Seventeen patients received melphalan and prednisone, and one patient received chlorambucil and prednisone. All of the patients had some impairment of renal function at presentation, and 58% had a serum creatinine concentration greater than 354 mumol/L (4.0 mg/dL). There was either stabilization or improvement in renal function after chemotherapy in five of eight patients who had a serum creatinine concentration less than 354 mumol/L (4.0 mg/dL) at the initiation of therapy. Of the 11 patients with a high serum creatinine concentration (greater than 354 mumol/dL [4.0 mg/dL]), 82% progressed to end-stage renal disease despite therapy. Follow-up urine protein studies demonstrated at least a 50% decrease in urine protein excretion in five of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypergammaglobulinemia; Immunoglobulin Light Chains; Kidney Diseases; Male; Melphalan; Middle Aged; Prednisone; Retrospective Studies; Survival Analysis; Time Factors

Topics: Animals; Bence Jones Protein; Blood Viscosity; Cat Diseases; Cats; Dog Diseases; Dogs; Hemorrhagic Disorders; Hypercalcemia; Hypergammaglobulinemia; Kidney Diseases; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Waldenstrom Macroglobulinemia

Topics: Adult; Amyloidosis; Antigens; Cadaver; Colchicine; Female; Humans; Immune Complex Diseases; Immunoglobulin Light Chains; Kidney; Kidney Diseases; Kidney Transplantation; Male; Melphalan; Middle Aged; Postoperative Complications; Remission, Spontaneous; Renal Dialysis; Transplantation, Homologous

A 41-year-old woman, presenting with renal failure, renal glucosuria and moderate anemia, was found to have light chain myeloma, indicated by a kappa chain M-component in the serum, heavy urinary excretion of kappa chains and plasma cell infiltration of the bone marrow. After administration of one course of melphalan, resulting in transient pancytopenia, the light chains disappeared completely, renal function returned to normal, glucosuria disappeared and the Hb concentration normalized. During an observation period of six years she has remained in good health and there has been no sign of relapse.

Topics: Adult; Female; Glycosuria; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Kidney Diseases; Leukopenia; Melphalan; Multiple Myeloma; Remission, Spontaneous; Time Factors

This group of proliferative diseases of the plasma cell line, in which manifestations of abnormal immunoglobulin production are associated with variable degrees of depressed antibody synthesis, pose fascinating problems crossing many clinical and research disciplines. The present state of diagnosis and clinical management is assessed.

Topics: Alkylating Agents; Amyloidosis; Antibodies, Anti-Idiotypic; Bence Jones Protein; Blood Cell Count; Blood Proteins; Bone Marrow; Bone Marrow Cells; Cyclophosphamide; Drug Therapy, Combination; Heavy Chain Disease; Humans; Immunoelectrophoresis; Immunoglobulins; Kidney Diseases; Melphalan; Multiple Myeloma; Prednisone; Proteinuria

Topics: Amyloidosis; Cyclophosphamide; Humans; Kidney Diseases; Male; Melphalan; Middle Aged

Topics: Allopurinol; Bence Jones Protein; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Male; Melphalan; Multiple Myeloma; Myeloma Proteins; Prednisone; Proteinuria

Topics: Adult; Aged; Amyloid; Amyloidosis; Bence Jones Protein; Biopsy; Blood Protein Disorders; Electrophoresis; Female; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Proteinuria; Time Factors

Topics: Adolescent; Antibodies, Antinuclear; Autoantibodies; Betamethasone; Female; Hepatitis; Humans; Immune Tolerance; Immunosuppressive Agents; Kidney Diseases; Lupus Erythematosus, Systemic; Melphalan; Methotrexate; Neutrophils; Prednisone; Splenectomy