melphalan and Kidney-Failure--Chronic

Systemic AL amyloidosis is a rare complication of monoclonal gammopathies. Renal manifestations are frequent, mostly characterized by heavy proteinuria, with nephrotic syndrome and renal failure in more than half of the patients at diagnosis. Without treatment, median survival does not exceed 12 months. Amyloid heart disease and diffusion of amyloid deposits are associated with reduced survival. Treatment of systemic AL amyloidosis has been profoundly modified with the introduction of international criteria for the definition of organ involvement and hematologic response, and with the use of sensitive tests for the measurement of serum-free light chain levels. Melphalan plus dexamethasone is now established as the gold standard for first line treatment of systemic AL, with similar efficacy and reduced treatment-related mortality compared to high-dose therapy. Modern chemotherapy regimens, based on the use of novel agents such as bortezomib and lenalidomide, might further improve patient survival.

Topics: Amyloid; Amyloidosis; Biomarkers; Boronic Acids; Bortezomib; Cardiomyopathies; Consensus Development Conferences as Topic; Dexamethasone; Drug Therapy, Combination; Heart Transplantation; Humans; Immunoglobulin Light Chains; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Transplantation; Lenalidomide; Melphalan; Natriuretic Peptide, Brain; Paraproteinemias; Paraproteins; Peptide Fragments; Prognosis; Pyrazines; Randomized Controlled Trials as Topic; Renal Dialysis; Thalidomide

Renal failure, mostly related to myeloma cast nephropathy (MCN), is a frequent complication of multiple myeloma (MM), which occurs in up to 50% of patients during the course of the disease. Persistent renal failure in MM is associated with poor survival. Treatment of MCN relies on urgent symptomatic measures (alkalinisation, rehydration, correction of hypercalcemia, and withdrawal of nephrotoxic drugs), with rapid introduction of chemotherapy to efficiently reduce the production of monoclonal light chains (LC). Recent studies suggest that, in patients with MM and severe renal failure due to MCN, rapid removal of circulating LC, through intensive hemodialysis sessions using a new generation high cut-off dialysis membrane, might result in dialysis withdrawal in most patients. If the development of intensive therapy and new efficient chemotherapy agents (thalidomide, bortezomib, lenalidomide) has transformed the care and prognosis of MM, the modalities and safety of these therapeutic regimens in patients with renal failure remain to be defined. The association of bortezomib with dexamethasone should be considered currently as first-line treatment in patients with MM and impaired renal function.

Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Clinical Trials as Topic; Contraindications; Cyclophosphamide; Dexamethasone; Fluid Therapy; Humans; Hypercalcemia; Immunoglobulin Light Chains; Kidney Failure, Chronic; Lenalidomide; Melphalan; Multicenter Studies as Topic; Multiple Myeloma; Myeloma Proteins; Prospective Studies; Protease Inhibitors; Pyrazines; Randomized Controlled Trials as Topic; Renal Dialysis; Thalidomide

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

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

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

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

Topics: Alkylating Agents; Amyloidosis; Anemia; Anemia, Refractory; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Blood Transfusion; Bone and Bones; Bone Marrow Examination; Bone Marrow Transplantation; Bone Neoplasms; Calcium; Combined Modality Therapy; Diagnosis, Differential; Heavy Chain Disease; Humans; Immunoglobulin D; Immunotherapy; Interferons; Kidney Failure, Chronic; Leukemia; Melphalan; Mice; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Myeloma Proteins; Osteolysis; Osteosclerosis; Paraproteinemias; Plasma Cells; Plasmacytoma; Prednisone; Radionuclide Imaging; Waldenstrom Macroglobulinemia

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

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

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

The basic pathologic process in multiple myeloma is the neoplastic proliferation of a single clone of plasma cells. Although the events which trigger autonomous cell growth are not well understood, the secretion of an M component, a serum or urinary immunoglobulin molecule or a light chain fragment by the vast majority of myeloma cells has provided a biologic marker which has greatly facilitated the study of this disease Some of the more recent clinical concepts which have evolved from studies on the plasma cell and the immunoglobulin molecule are discussed.

Topics: Alkylating Agents; Amyloidosis; Bacterial Infections; Blood Viscosity; Bone Diseases; Clone Cells; Hemostasis; Humans; Hypercalcemia; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Paraproteins

The impact of high dose dexamethasone containing regimens with or without the novel agents thalidomide and bortezomib on the reversal of renal failure (RF) was evaluated in 41 consecutive newly diagnosed patients with multiple myeloma (MM) treated in a single institution. RF was reversed in 73% of all patients within a median of 1.9 months. In patients treated with dexamethasone and novel agents (thalidomide and/or bortezomib) the reversibility rate was 80% within a median of 0.8 months. Severe RF and significant Bence Jones proteinuria were associated with a lower probability of RF reversal. Patients who responded to treatment achieved RF reversal more often than in those who did not (85% versus 56%, p=0.046). In conclusion, RF is reversible in the majority of newly diagnosed MM patients treated with high-dose dexamethasone containing regimens. The addition of novel agents induces a more rapid RF reversal.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Boronic Acids; Bortezomib; Dexamethasone; Doxorubicin; Female; Humans; Hypercalcemia; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Proteinuria; Pyrazines; Thalidomide; Treatment Outcome; Vincristine

Haematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan-prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3-4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of >50, 30-50 and <30 ml/min respectively. WHO grades 3-4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a clearance of < or =10 ml/min no conclusions can be drawn for this subgroup.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Retrospective Studies; Survival Rate

The development of end-stage renal disease (ESRD) is common among patients with amyloid light-chain AL amyloidosis-associated renal disease and survival of these patients is poor. High-dose intravenous melphalan and autologous stem cell transplantation induce remission of the plasma cell dyscrasia in a significant proportion of patients with AL amyloidosis. The efficacy and tolerability of such treatment for patients with AL amyloidosis-associated ESRD are unknown.. Between June 1994 and June 2000, 15 patients with AL amyloidosis-associated ESRD were treated with intravenous melphalan (70 to 200 mg/m2) and autologous peripheral blood stem cell transplantation. Clinical and laboratory data were prospectively collected prior to treatment, during the peritransplant period, and at 3 months, 12 months, and annually thereafter. Treatment outcomes and toxicities were compared with 180 non-ESRD patients treated during the study period.. Eight of 15 patients (53%) had a hematologic complete response following treatment. Two patients (13%) died during the peritransplant period. Transfusion requirements were greater and there was a trend toward increased severity of mucositis in the ESRD patients compared with the non-ESRD patients. Median survival for the ESRD patients with a hematologic complete response was 4.5 years. Five patients with hematologic complete response have either undergone or are awaiting renal transplantation.. High-dose intravenous melphalan with stem cell transplantation is an effective treatment in selected patients with AL amyloidosis-associated ESRD. Although the toxicity profile is greater in ESRD patients, the treatment offers the possibility of successful renal transplantation if hematologic remission is achieved. This treatment should be considered for patients with AL amyloidosis-associated ESRD.

Topics: Adult; Aged; Amyloidosis; Antineoplastic Agents, Alkylating; Female; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Prospective Studies; Remission Induction; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous

36 MM pts in advanced stage, 17 recently diagnozed (group I) and 19 in the progression of the disease (group II) were examined. 10 pts of group I and 12 of group II had renal failure. Levels of II-6, sII-6R and TNF-alpha were measured in pts sera before cytostatic therapy or plasma exchange (PE) and after 4-week therapy. The plasma concentration of II-6, sIl-6R and TNF-alpha before chemotherapy were 47-426 pg/ml, 33-III ng/ml and 19-350 pg/ml respectively and were significantly higher than in healthy control (group III) but no significant changes were observed between group I and group II. Patients with renal failure showed significantly higher II-6 and sIl-6R plasma levels than those with normal renal function. After 4 weeks of chemotherapy plasma concentration of the examined parameters decreased only in those pts of both groups, who later, after 6 mos disclosed a therapeutic response. Median survival time (m-ST) of recently diagnosed MM pts was 38 mos and in those with progression of underlying disease-43 mos. M-ST of 5 pts whose levels of Il-6 > 150 pg/ml, sIl-6R > 55 ng/ml and TNF-alpha-150 pg/ml was only 18 mos, but when only one of them was so much elevated it attained 55 mos. (p = 0.01).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Disease Progression; Female; Humans; Interleukin-6; Kidney Failure, Chronic; Male; Melphalan; Methylprednisolone; Middle Aged; Multiple Myeloma; Prednisone; Receptors, Interleukin; Receptors, Interleukin-6; Recombinant Fusion Proteins; Survival Rate; Tumor Necrosis Factor-alpha; 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

The kidney is the most common organ affected by immunoglobulin light-chain (AL) amyloidosis and monoclonal immunoglobulin deposition disease (MIDD), often leading to end-stage renal disease (ESRD). High-dose melphalan and stem cell transplantation (HDM/SCT) is effective for selected patients with AL amyloidosis, with high rates of complete hematologic response and potential for improved organ dysfunction. Data on tolerability and response to HDM/SCT in patients with ESRD due to AL amyloidosis and MIDD are limited. We analyzed data on toxicity, efficacy, and hematologic and renal response of HDM/SCT in 32 patients with AL amyloidosis and 4 patients with MIDD who were dialysis-dependent for ESRD treated at Boston Medical Center between 1994 and 2016. The most common grade 3/4 nonhematologic toxicities were infections (75%), metabolic abnormalities (56%), mucositis (42%), constitutional symptoms (39%), pulmonary complications (39%), and diarrhea (28%). Treatment related mortality (defined as death within 100 days of SCT) occurred in 8% (3 of 36). A complete hematologic response was achieved in 70% of evaluable patients (19 of 27) at 1 year after HDM/SCT. In the entire cohort, median overall survival (OS) after HDM/SCT was 5.8 years; median OS was 1 year for those who did not achieve a complete hematologic response and 8 years for those who did achieve a complete hematologic response. Twelve patients (33%) underwent kidney transplantation after successful treatment with HDM/SCT at a median of 2.4 years after SCT. HDM/SCT is safe and effective in inducing hematologic complete responses and prolonging survival in patients with ESRD from AL amyloidosis and MIDD. Achievement of a durable hematologic response can make these patients possible candidates for renal transplantation.

Topics: Adult; Aged; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney Failure, Chronic; Kidney Transplantation; Male; Melphalan; Middle Aged; Renal Dialysis; Stem Cell Transplantation; Treatment Outcome

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

The following case shows corneal crystal formation in a patient in whom thee systemic work-up led to the diagnosis of a monoclonal gammopathy with increased monoclonal immunoglobulin G (IgG). We present the corneal signs and subsequent haematological investigations undertaken to establish this important association.. Systemic work-up of a patient with corneal deposits showed a monoclonal gammopathy with increased monoclonal immunoglobulin (IgG-type kappa). Corneal crystals, a rare, but significant, clinical finding, may be the initial presentation in a patient with monoclonal gammopathy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Combined Modality Therapy; Corneal Opacity; Crystallization; Cyclophosphamide; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin kappa-Chains; Kidney Failure, Chronic; Lenalidomide; Male; Melphalan; Middle Aged; Paraproteinemias; Paraproteins; Phacoemulsification; Postoperative Complications; Prednisone; Slit Lamp; Thalidomide

Topics: Antineoplastic Combined Chemotherapy Protocols; Benzylamines; Combined Modality Therapy; Cyclams; Dexamethasone; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds; Humans; Kidney Failure, Chronic; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Receptors, CXCR4; Renal Dialysis; Thalidomide; Transplantation Conditioning

Light-Chain Deposition Disease (LCDD) frequently recurs after renal transplantation, displaying a pernicious course. Herein we have described a 39-year-old Caucasian man with a history of immunoglobulin G-kappa multiple myeloma who failed two chemotherapy regimens, but ultimately responded to the combination of thalidomide, bortezomib, and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation 3 years prior to transplantation, during which time he showed no evidence of persistent or recurrent disease. At 3 days following spousal living related renal transplantation, he displayed a rapid deterioration of renal function requiring dialysis therapy. This episode failed to respond to empiric antirejection therapy including anti-thymocyte globulin, plasmapheresis, and anti-CD20 monoclonal antibody. Increasing evidence suggested recurrence of LCDD, including positive immunofluorescence staining of basement membranes and vessels for kappa light chains as well as free kappa light chains in his urine and serum. Following suspension of sirolimus, he was initiated on and responded to bortezomib (1.3 mg/m(2)) with discontinuation of dialysis within 3 weeks and progressively improving renal function. His maintenance therapy, in addition to six 2-week-long cycles of bortezomib separated by 1-week rest periods, includes cyclosporine (50 mg twice daily), prednisone (10 mg daily), and curcumin (9 g daily). In sum, bortezomib rescue therapy salvaged a spousal renal transplant afflicted with recurrent LCDD.

Topics: Adult; Antilymphocyte Serum; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Pyrazines; Recurrence; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Multicentric Castleman disease is a systemic lymphoproliferative disease with incomplete understood etiology. The various renal complications of this disease may include minimal change disease, mesangial proliferative glomerulonephritis, membranous glomerulonephritis and nephrotic syndrome, caused by secondary amyloidosis. In several reported cases of localized Castleman disease associated with renal amyloidosis and nephrotic syndrome, resection of organs involved by lymphoid proliferation resulted in complete remission. However, therapy of multicentric Castleman disease with renal amyloidosis is not well-established. We treated a case of a 39-year-old woman with multicentric Castleman disease complicated by nephrotic syndrome caused by secondary AA amyloidosis. The patient underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), achieving complete remission. Autologous stem cell transplantation may be an attractive choice in therapy for refractory multicentric Castleman disease.

Topics: Adult; Amyloidosis; Castleman Disease; Female; Humans; Kidney Failure, Chronic; Melphalan; Myeloablative Agonists; Nephrotic Syndrome; Peripheral Blood Stem Cell Transplantation

To analyse clinical picture of multiple myeloma (MM) and treatment results in MM patients on programmed dialysis (PD).. Case histories of 22 MM patients were analysed. They had a terminal stage of chronic renal failure (CRF) in the onset of the disease. Chemotherapy (CT) was performed in 20 patients (10 patients received VAD program, the other 10--melfalan).. Early lethality was 28%. The patients died of septic complications. Neutropenia was observed significantly more frequently on melfalan treatment than on VAD therapy (9 and 2 patients, respectively; chi-square 5.6; p = 0.009). Survival median, excluding early lethality, was 16 months. Differences by therapy were not registered. Three patients on MP program survived more than 3 years. Function of the kidneys improved in 4 (20%) patients. Hemodialysis was avoided in 2 patients. Survival of patients with reestablished renal function was maximal (44 and 84 months).. Standard CT for MM with terminal CRF is associated with high toxicity and frequent septic complications. Survival is better if renal function improves and HD discontinues. Reversibility of CRF at a terminal stage in MM does not depend on completeness of hematological response. Programs with melfalan CT provoke more frequent myelotoxic cytopenia, early lethality is higher but the number of longer survivals is more.

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Renal Dialysis; Retrospective Studies; Survival Rate; Treatment Outcome

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

Topics: Amyloidosis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Melphalan; Stem Cell Transplantation; Transplantation, Autologous

To evaluate the role of high-dose melphalan and autologous transplant (AT) in reversing dialysis-dependent renal failure, 59 patients still on dialysis at the time of AT were analyzed. A total of 37 patients had been on dialysis < or =6 months. A 5-year event-free and overall survival rate of all patients after AT was 24 and 36%, respectively. Of 54 patients evaluable for renal function improvement, 13 (24%) became dialysis independent at a median of 4 months after AT (range: 1-16). Dialysis duration < or =6 months prior to first AT and pre-transplant creatinine clearance >10 ml/min were significant for renal function recovery: 12 of 36 (33%) < or =6 months vs one of 18 patients (6%) >6 months on dialysis recovered renal function; 10 of 26 (38%) with >10 ml/min vs three of 28 (11%) with < or =10 ml/min of creatinine clearance (both P<0.05). Quality of response after autotransplant was also significant: 12 of 31 (39%) being greater than partial remission after AT vs one of 21 patients (5%) attaining partial remission or less became independent of dialysis (P<0.05). Our data suggest that significant renal failure can be reversible and AT should be considered early in the disease course.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Prognosis; Renal Dialysis; Transplantation, Autologous

Specific treatment of light-chain deposition disease has been reported as ineffective in altering the course of the severe or end-stage renal failure it causes. The authors describe a case of biopsy-proven primary light-chain deposition disease of the kidney, severe renal failure, and incipient dialysis dependency, treated by autologous peripheral blood stem cell transplantation, that led to reversal of dialysis dependency and sustained improvement in renal function.

Topics: Antineoplastic Agents, Alkylating; Humans; Immunoglobulin Light Chains; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Remission Induction; Renal Dialysis; Transplantation, Autologous

The disease-free survival of patients with myeloma and severe renal failure after high-dose melphalan and autologous stem cell rescue is similar to those with normal renal function at the time of the autograft. However, recovery of renal function after intensive treatment is uncommon and patients with end-stage renal failure continue to be dialysis-dependent. We report two patients with myeloma who required regular haemodialysis from diagnosis, but became dialysis-independent after a high-dose melphalan autograft. Thus, in some patients, renal function may be partially salvageable despite the requirement for dialysis at the time of autografting.

Topics: Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Melphalan; Middle Aged; Multiple Myeloma; Transplantation, Autologous

Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15 microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/microI and 20000 platelets/microI were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cholangiocarcinoma; Combined Modality Therapy; Creatinine; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Immunologic Factors; Interferon-alpha; Kidney Failure, Chronic; Male; Melphalan; Metabolic Clearance Rate; Middle Aged; Multiple Myeloma; Neoplasms, Second Primary; Remission Induction; Renal Dialysis; Safety; Stomatitis; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Vincristine

Renal function is one of the most important prognostic factors in multiple myeloma (MM). Patients with renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy schemes. The aim of this study was to analyze the outcome of MM patients with renal insufficiency undergoing autologous stem cell transplantation (ASCT), including the evaluation of the quality of PB stem cell collections, kinetics of engraftment, transplant-related mortality, response to high dose chemotherapy and survival.. From a total of 566 valuable patients included in the MM Spanish ASCT registry, three groups of patients were defined: group BA, patients with abnormal renal function at diagnosis but normal at transplant (73 cases); group BB, patients with abnormal function both at diagnosis and at transplant (14 cases); and group AA (control group, 479 cases), patients who constantly had normal renal function.. Patients from groups BA and BB presented with a significantly higher number of adverse prognostic factors, reflecting that we were dealing with high tumor MM cases, as compared with patients from group AA. The number of mononuclear cells, CD34+ cells and CFU-GM cells collected in patients with non-reversible renal insufficiency was similar to those harvested in MM patients with normal renal function. Moreover, neutrophil and platelet engraftments were identical in patients with and without renal failure (days +11 and +12, respectively). By contrast, transplant-related mortality (TRM) was significantly higher in group BB patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate analysis only three variables showed independent influence on TRM: poor performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine > or =5 mg/dl. The response to high dose therapy was independent of renal function. Interestingly, 43% of patients from group BB showed an improvement in renal function (creatinine < 2 mg/dl) after transplant. The three-year overall survival from transplantation was 56, 49 and 61% for the BB, BA and AA groups, respectively, with a statistically significant difference favoring group AA (P<0.01). PFS did not differ significantly between the three groups of patients. In multivariate analysis the only unfavorable independent prognostic factors for overall survival were poor performance status either at diagnosis or at transplant, high beta(2)-microglobulin levels, and no response to transplant. According to these results, ASCT is an attractive alternative for MM patients with renal insufficiency, and it should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl).

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Staging; Registries; Retrospective Studies; Spain; Transplantation, Autologous; Treatment Outcome

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

Despite significant effects of melphalan and prednisone in the therapy of systemic AL-amyloidosis, overall prognosis is poor and remission of clinical symptoms cannot generally be expected. The course of the disease and results of therapy are possibly influenced by the degree and distribution of organ manifestation at the time of diagnosis. We report a group of patients with renal involvement as the main manifestation of disease.. Fifteen patients with systemic Al-amyloidosis without symptomatic myeloma (4 women, 11 men, median age 61 [34 to 71] years) have been attended to at our department and were treated throughout the course of the disease.. Since primary symptoms were frequently unspecific, the maximum time to diagnosis came to 28 months. Renal involvement was primarily evident at the time of diagnosis when all patients manifested proteinuria or renal insufficiency. Ten patients were treated with a melphalan and prednisone containing chemotherapeutic protocol. A significant clinical improvement was observed in no case. One patient in an advanced stage of disease died after the administration of a high-dose regimen of melphalan with blood stem-cell support subsequent to sepsis.. We do not see an absolute indication for chemotherapy. The unfavorable prognosis--14 patients died an average of 13 months after diagnosis--requires a particularly careful consideration of potential benefits and possible risks accompanying cytostatic therapy.

Topics: Adult; Aged; Amyloidosis; Edema; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Paresthesia; Prednisone; Prognosis; Proteinuria; Survival Rate

High dosage melfalan chemotherapy with subsequent autologous blood stem cell transplantation in suitably selected patients with multiple myeloma greatly increases the probability that complete remission will be achieved and it prolongs the mean survival period as compared with classical chemotherapy. Till recently patients with multiple myeloma and renal insufficiency were not included in transplantation programmes. Only recently several papers were published abroad which indicate the possibility to implement transplantations also in these patients. The authors describe the treatment, incl. the first autologous transplantation of blood stem cells in a patient with multiple myeloma and renal insufficiency.

Topics: Adult; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Kidney Failure, Chronic; Male; Melphalan; Multiple Myeloma

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.

Topics: Adolescent; Adult; Aged; Amyloidosis; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Melphalan; Middle Aged; Multiple Myeloma; Peritoneal Dialysis, Continuous Ambulatory; Prednisolone; Renal Dialysis; Retrospective Studies; Survival Rate

Overall 30 patients with multiple myeloma (MM) were examined for immunological and rheological parameters. MM was shown to be marked by imbalance of immunobiological reactivity, with the greatest changes being seen in the B cell immunity system. MM is also characterized by marked rheological shifts related to the immunological alterations and underlying the hyperviscosity syndrome and heart failure. Administration of polychemotherapy resulted in a decrease of the count of B lymphocytes, circulating immune complexes; a tendency toward normalization of the rheological blood properties was observed. Introduction of plasmapheresis into the treatment program of the patients noticeably raised the treatment efficacy.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Viscosity; Chronic Disease; Cyclophosphamide; Daunorubicin; Female; Heart Failure; Humans; Immunity, Cellular; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Nitrogen Mustard Compounds; Prednisolone; Vincristine

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

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

The pharmacokinetics of the alkylating agent melphalan was determined in a dialysed patient, 30 years old, who underwent unilateral orchidectomy for a malignant testicular tumor. Melphalan was included in a polychemotherapy treatment with eight 1-h infusions of 230 mg of etoposide (VP 16), then one 5-min infusion of 370 mg of melphalan (200 mg/m2) followed by autologous bone marrow grafting (ABMG). In this patient, melphalan pharmacokinetics was different from that of patients without important renal dysfunction for the area under the concentration curve (1,324 mg.l-1.min). However, with a melphalan elimination half-life of 80 min, ABMG could be performed, as usually, 24 h after melphalan administration. Plasma alpha-fetoprotein (AFP) concentrations showed that chemotherapy was efficient. Furthermore, we observed a modification of etoposide kinetics due to melphalan.

Topics: Adult; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Humans; Kidney Failure, Chronic; Male; Melphalan; Teratoma; Testicular Neoplasms

The presenting clinical features, response to treatment and survival duration of 26 consecutive multiple myeloma patients with renal failure at diagnosis were investigated. All but 1 of the patients had high tumour cell mass stage, as identified by one (3 cases) or more (22 cases) of the criteria defined by Durie and Salmon. Survival length of azotaemic patients was significantly shorter than that of stage III patients with normal renal function (median: 4 months vs 41 months, respectively, P less than 0.0005), and was positively affected by reversal of renal failure following treatment (P less than 0.0005). Of the 26 patients, 56% achieved reversal of renal failure. Recovery of normal renal function was prompt in most of the cases and appeared to be independent from both M component type and pretreatment serum creatinine levels. Finally, it was shown that patients with reversible renal impairment but with myeloma unresponsive to alkylating agents had early recurrence of impaired renal function and a shorter life expectancy than patients with a significant decrease in tumour cell mass.

Topics: Adrenal Cortex Hormones; Adult; Aged; Calcium; Female; Follow-Up Studies; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Prognosis

A series of nine consecutive patients with multiple myeloma and renal failure is presented. All patients were treated with urinary alkalinisation with sodium bicarbonate and/or acetazolamide, diuresis with saline, mannitol and/or furosemide, pulse melphalan and prednisone and, where indicated, allopurinol and aluminium hydroxide. A substantial and sustained improvement in renal function has been achieved in all nine patients. Of five patients with a urea more than 25 mmol/L at presentation, the median survival to date is 64 weeks. Of these patients only one has died --not from renal failure but pneumonia, eighteen months after presentation. The others are alive and well. The results confirm the effectiveness of these measures in both improving renal function and prolonging survival, and suggest a more optimistic prognosis for patients with multiple myeloma and renal failure.

Topics: Adult; Aged; Creatinine; Diuretics; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Peritoneal Dialysis; Prednisone; Prognosis; Time Factors; Urea

A rarely diagnosed nodular glomerulopathy is presented arising secondary to kappa light chain deposition and clinically characterized by hypertension, congestive heart failure, massive proteinuria and slowly progressive azotemia. Kappa light chains were detected in the urine, the glomerular nodules, and the basement membranes of both glomeruli and tubules. A malignant proliferation of plasma cells could not be detected. Two morphologic features were unusual: the presence of microaneurysms, and the deposition of immunoglobulin and complement in a similar pattern to the kappa light chains. Noteworthy clinical aspects included the elusiveness of the proper diagnosis, the massive proteinuria in the absence of amyloid deposits, and the remarkable improvement in renal function following intermittent chemotherapy.

Topics: Aged; Female; Humans; Immune Complex Diseases; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Kidney Failure, Chronic; Kidney Glomerulus; Melphalan; Prednisone; Renal Dialysis; Vincristine

The patients entered into the Medical Research Council's First Myelomatosis Trial (MRCI) have been followed up for a minimum of 12 years, and an attempt has been made to define features recorded at presentation that might predict long-term survival and to estimate the risk of acute myeloid leukaemia (AML) induced by treatment with either of the alkylating agents, melphalan or cyclophosphamide. In this series, the chance of a patient surviving 5 years was strongly related to the haemoglobin, blood urea concentration (BUC) and performance status at presentation. Other features, including paraprotein levels, type of heavy or light chain, bone lesions and recovery of polyclonal immunoglobulin added little useful information. Six patients died of AML, all after more than 4 years in the trial; the incidence of AML among 4-year survivors was 10%. All six patients had been treated with continuous melphalan and the implications of this for future chemotherapy for myelomatosis are discussed.

Topics: Aged; Bence Jones Protein; Cyclophosphamide; Female; Hemoglobins; Humans; Immunoglobulin G; Kidney Failure, Chronic; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteins; Prognosis; Time Factors; Urea

Topics: Adult; Aged; Cyclophosphamide; Drug Evaluation; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloma Proteins; Neoplasm Staging; Time Factors

Plasmocytoma is generally a systemic disorder and has to be differentiated from solitary plasmocytoma of bones and connective tissue. Diagnosis is based on the typical bone marrow findings, the demonstration of monoclonal paraprotein and the radiological skeletal changes. Prognosis is poor, life expectancy limited to about 18 months. Specific therapy with cytotoxic drugs leads in many cases to marked improvement of the general condition, relative freedom of pain and a decreased complication rate.

Topics: Aged; Aging; Bence Jones Protein; Bone Marrow Cells; Cyclophosphamide; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Osteoporosis; Plasma Cells; Plasmacytoma; Prognosis; Vincristine

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

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

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

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

Topics: Aged; Antineoplastic Agents; Female; Humans; Kidney Failure, Chronic; Leukemia, Plasma Cell; Male; Melphalan; Microscopy, Electron; Microscopy, Fluorescence; Microscopy, Phase-Contrast; Middle Aged; Neoplastic Cells, Circulating; Prednisolone

Topics: Blood Urea Nitrogen; Creatinine; Cyclophosphamide; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma; Proteinuria; Renal Dialysis

Topics: Adrenal Cortex Hormones; Aged; Androgens; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Multiple Myeloma

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