melphalan and Heart-Diseases

Intensive therapy and autologous marrow or peripheral blood stem cell transplantation is often utilized in Hodgkin's disease patients whose disease has progressed after primary conventional chemotherapy. A number of studies have described long-term disease-free survival in up to 50% of transplanted patients. High-dose chemotherapy conditioning regimens such as "CBV" or "BEAM" have been used more often than regimens containing total body irradiation. Usually unpurged autologous bone marrow has been utilized as the source of hematopoietic stem cell reconstitution, although recently the use of "primed" peripheral blood stem cells has increased markedly. The challenges of transplant-related toxicity and recurrence of disease post-transplant are discussed, as well as possible strategies to reduce these problems. The use of autologous transplantation is discussed in three clinical settings: patients who have failed to enter a complete remission (CR) after primary chemotherapy, those who have relapsed within 12 months of attaining a CR and those who have relapsed after a longer (i.e., > or = 12 months) first CR. When compared with conventional salvage chemotherapy, transplantation appears to produce a higher long-term disease-free survival rate in all of these patient groups. However, assessment of an advantage for autotransplantation, particularly in patients with long first remissions, is difficult without a Phase III trial. On the other hand, recently updated results from our center indicate that 72% of patients relapsing after long initial remissions benefit from autotransplantation at this point in their disease course, and that transplant-related mortality is low in this setting. Other issues addressed include the potential role of autologous transplantation as consolidation therapy in selected high-risk patients in an initial CR, as well as the utility of conventional chemotherapy and involved-field radiotherapy in conjunction with autotransplantation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Digestive System Diseases; Etoposide; Heart Diseases; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lung Diseases; Melphalan; Multicenter Studies as Topic; Podophyllotoxin; Recurrence; Remission Induction; Salvage Therapy; Survival Rate; Treatment Outcome; Whole-Body Irradiation

Cardiac involvement in light-chain amyloidosis (AL) predicts poor prognosis and is associated with higher TRM and morbidity during high-dose therapy and auto-SCT (HDT-ASCT). We studied the outcomes of 30 patients with cardiac amyloidosis undergoing HDT-ASCT at our center between January 1998 and March 2012. The median age of the patients was 53 years (range, 36-74) with a median follow-up of 35 months (range, 0.4-97 months). Twenty-seven patients (90%) had more than one organ involved besides the heart with 37% with cardiac stage ⩾3. Melphalan-based conditioning regimen (140-200 mg/m(2)) was used for HDT-ASCT. One-year TRM is 10%. Three-year OS and EFS from HDT-ASCT was 83% and 56.8%, respectively. Cumulative incidence of relapse at 3 years was 38.5%. Negative factors affecting survival included age >60 years, lack of novel induction therapy and BM plasmacytosis >10%. We conclude that HDT-ASCT is well tolerated in patients with high-risk cardiac amyloidosis and can lead to improved overall outcomes.

Topics: Adult; Aged; Amyloidosis; Autografts; Disease-Free Survival; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Recurrence; Stem Cell Transplantation; Survival Rate; Transplantation Conditioning

In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

Topics: Aged; Amyloidosis; Biomarkers; Female; Follow-Up Studies; Heart Diseases; Hematopoietic Stem Cells; Humans; Immunoglobulin Light-chain Amyloidosis; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Retrospective Studies; Stem Cell Transplantation; Time Factors; Treatment Outcome; Troponin I

Immunoglobulin light chain amyloidosis remains incurable despite recent therapeutic advances, and is particularly difficult to treat in patients with amyloid cardiomyopathy. Based on evidence of activity in multiple myeloma, we designed a pilot study of an oral regimen of lenalidomide in combination with dexamethasone and low-dose melphalan in order to evaluate its safety and efficacy in patients with amyloidosis, including those with advanced cardiac involvement. Twenty-five patients were enrolled. Ninety-two percent of patients had cardiac involvement by amyloidosis, and 36% of patients met the criteria for Mayo Clinic cardiac stage III disease. Patients received up to nine cycles of treatment, consisting of lenalidomide 10 mg/day orally on days 1 - 21 (28-day cycle); melphalan 0.18 mg/kg orally on days 1-4; and dexamethasone 40 mg orally on days 1, 8, 15, and 22. High rates (33%) of cardiac arrhythmias and low rates of treatment completion (12.5%) were observed. Ten patients died during the study, all within the first several months of treatment due to acute cardiac events. The overall hematologic response rate was 58%, however organ responses were seen in only 8% of patients. The overall survival rate at 1 year was 58%. While we confirmed the hematologic response rates observed with similar regimens, front-line treatment with melphalan, lenalidomide and dexamethasone was toxic, ineffective, and did not alter survival outcomes for patients with high-risk cardiac disease. Our data highlight the importance of developing novel treatment approaches for amyloid cardiomyopathy. This trial was registered at www.clinicaltrials.gov (NCT00890552).

Topics: Aged; Aged, 80 and over; Amyloidosis; Cohort Studies; Dexamethasone; Drug Therapy, Combination; Female; Heart Diseases; Humans; Immunoglobulin Light Chains; Lenalidomide; Male; Melphalan; Middle Aged; Pilot Projects; Survival Rate; Thalidomide

Patients with primary (AL) amyloidosis and heart failure have a very poor prognosis and cannot tolerate aggressive therapy, such as autologous stem cell transplantation and high-dose dexamethasone-based regimens. We prospectively treated 22 patients with advanced cardiac amyloidosis combining oral melphalan, thalidomide, and reduced intensity dexamethasone (MTD). Six patients died due to cardiac amyloidosis before completing cycle 3. Early death was associated with reduced ejection fraction. Eight patients achieved a hematological response and four achieved a durable improvement of cardiac dysfunction. Treatment with MTD is feasible in patients with advanced cardiac AL amyloidosis and effective in subjects with preserved systolic function.

Topics: Aged; Amyloidosis; Dexamethasone; Drug Therapy, Combination; Female; Heart Diseases; Heart Failure; Humans; Male; Melphalan; Middle Aged; Stroke Volume; Survival Rate; Thalidomide; 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

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

High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated mainly because of the high treatment-related mortality (24% in a randomised study comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long-term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden between 1994 and 2009. Seventy-two patients were treated at eight Swedish centres. Median follow-up was 67.5 months. At least partial response (organ or haematological) was seen in 64% of the patients. Median overall survival was 98 months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In patients with cardiac involvement or multiple organ involvement, survival was significantly shorter, median overall survival 49 and 56 months, respectively. All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in the patients with cardiac involvement. For patients treated in the earlier time period (1994-2001), 100-day mortality was 23.8% compared with 7.8% in the later period (2002-2009). In conclusion, long survival times can be achieved in patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres. Early mortality is high, but with a decreasing trend over time.

Topics: Adult; Disease-Free Survival; Female; Follow-Up Studies; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Multiple Organ Failure; Survival Rate; Sweden; Time-to-Treatment; Transplantation, Autologous; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Atrial Fibrillation; Combined Modality Therapy; Disease-Free Survival; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Melphalan; Middle Aged; Multiple Myeloma; Multivariate Analysis; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduced-dose melphalan (100-160 mg/m(2)). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplantation; only low serum albumin predicted early deaths. Overall, hematologic response (HR) and cardiac responses were seen in 66% and 41% of patients, respectively. The median OS for patients with and without HR was not reached and 22 months, respectively (P < .01); and for those with any decrease and no decrease in N-terminal-pro-brain natriuretic peptide was not reached and 26 months, respectively (P < .01). In multivariate analysis of baseline factors, only reduced-dose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of HR and organ response is associated with improved survival.

Topics: Adult; Aged; Amyloidosis; Dose-Response Relationship, Drug; Feasibility Studies; Female; Follow-Up Studies; Heart Diseases; Humans; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Survival Analysis; Transplantation Conditioning

High-dose melphalan and autologous stem cell transplantation (HDM) is an effective treatment for systemic amyloid light chain (AL) amyloidosis but the eligibility criteria exclude many patients with this disorder. The aim of this study was to determine appropriate treatment strategies for systemic AL amyloidosis according to each patient's clinical condition in Japan.. Historical cohort study. Fifty-three patients with systemic AL amyloidosis (those with malignancies were excluded) were treated in our hospital with HDM (15 patients), melphalan + prednisolone (MP) (17 patients), vincristine + adriamycin + dexamethasone (VAD) (11 patients), or supportive treatment (no chemotherapy, 10 patients). We compared the survival rates among these treatment groups.. Mean survival was significantly longer in the HDM group than in the other three groups (P < 0.01, log-rank test). This trend remained the same when patients were divided into those with and without cardiac amyloid involvement. Furthermore, in patients with heart involvement, survival in the VAD therapy group was significantly inferior to that in the MP therapy group (P < 0.01 by log-rank test). Significant factors related to the survival rate included the presence or absence of heart involvement and treatment modality.. HDM should be considered the treatment of choice in eligible patients with systemic AL amyloidosis even in the presence of cardiac amyloidosis. If HDM is not eligible, indications for VAD therapy should be carefully evaluated in patients with cardiac amyloidosis.

Topics: Adult; Aged; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Combined Modality Therapy; Dexamethasone; Doxorubicin; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Diseases; Male; Melphalan; Middle Aged; Prognosis; Survival Rate; Vincristine

The prognosis in amyloid light chain (AL)-amyloidosis and multiorgan involvement is poor, with a high-treatment-related mortality after high-dose melphalan and autologous stem cell transplantation (HDM/SCT). Some patients, however, might benefit from the therapy. We report a case of cardiac AL-amyloidosis with multiorgan involvement where the progressive cardiomyopathy was halted after successful treatment with HDM/SCT in 2001. The patient is in an excellent cardiac condition with a good quality of life, receiving treatment with angiotensinogen receptor blockers and a flexible diuretics regimen at follow-up after 10 years.

Topics: Amyloidosis; Female; Follow-Up Studies; Gastrointestinal Diseases; Heart Diseases; Humans; Immunoglobulin Light Chains; Liver Diseases; Melphalan; Middle Aged; Myeloablative Agonists; Myocardium; Stem Cell Transplantation

Treatment with oral melphalan and dexamethasone (M-Dex) was reported to be effective and feasible in patients with systemic light chain amyloidosis (AL) not eligible for high-dose melphalan. We report on 61 patients with advanced AL who were treated with intravenous M-Dex as first-line therapy. Estimated median overall survival (OS) was 17.5 months. Seventeen patients (28%) died within 3 months, mostly of disease-related complications. In addition, nonhematologic toxicity of Common Terminology Criteria grade 3 or 4 was observed in 20 patients, whereas hematologic toxicity was low. Twenty-seven patients (44%) had hematologic response, including complete in 7 patients (11%) and partial remission in 20 patients (33%). Organ response was observed in 15 patients (25%). The amount of the involved free light chains in serum and Karnofsky Index at diagnosis significantly influenced OS. Plasma levels of the cardiac biomarkers before start of treatment and their increase after the third M-Dex cycle also were strong negative predictors of OS. These parameters might help to identify patients who will not benefit from M-Dex chemotherapy.

Topics: Adult; Aged; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Female; Heart Diseases; Humans; Immunoglobulin Light Chains; Injections, Intravenous; Lymphoproliferative Disorders; Male; Melphalan; Middle Aged; Prognosis; Retrospective Studies; Severity of Illness Index; Survival Analysis

The prognosis of advanced cardiac light-chain amyloidosis is poor. Heart transplantation might enable causative therapy and ultimately improve prognosis.. Nineteen patients with cardiac amyloidosis but no obvious involvement of other organs were scheduled for heart transplantation. Four to 6 months later, high-dose melphalan chemotherapy and autologous stem cell transplantation (HDM-ASCT) was planned in patients not in complete remission. Seven of nineteen patients died while waiting for heart transplantation. The remaining 12 patients (complete remission, n = 4) underwent surgery. Chemotherapy in patients not in complete remission consisted of HDM-ASCT (n = 5/12; subsequent complete remission, n = 2; partial remission, n = 3) or melphalan-prednisolone (partial remission, n = 1). Two of twelve patients were ineligible for any chemotherapy. Three of twelve patients died [423.5 (105-2131) days] from progressive disease, relapse, or sepsis. The 1- and 3-year survival rates were 83 and 83%, respectively, similar to those of patients undergoing heart transplantation for standard indications. Corresponding survival rates stratified by haematological response were 100 and 100% for complete remission (partial remission, 100 and 100%; progressive disease, 0 and 0%).. Heart transplantation in advanced cardiac amyloidosis is a promising approach to interrupting the vicious circle of ineligibility for potential curative chemotherapeutic treatment and extremely poor prognosis of cardiac amyloidosis without chemotherapy. Highly urgent heart transplantation combined with subsequent HDM-ASCT appears to offer a successful treatment option to improve the poor outcome of cardiac amyloidosis. However, it should be restricted to highly selected patients in specialized centres.

Topics: Amyloidosis; Cohort Studies; Combined Modality Therapy; Disease-Free Survival; Female; Graft Rejection; Graft Survival; Heart Diseases; Heart Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Male; Melphalan; Probability; Prognosis; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival Rate; Transplantation, Autologous; Treatment Outcome; Waiting Lists

Tandem autologous hematopoetic stem cell transplantation (HSCT) is an effective treatment in patients with multiple myeloma (MM). Patients receive high-dose cyclophosphamide (CY) followed by two myeloablative dosages of melphalan (MEL). Cardiotoxicity treatment related data are scanty. In 30 patients with MM chemotherapy was followed by high-dose CY (cycle CY), and two autologous tandem HSCT treatments with MEL (cycles MEL I and MEL II). During each 15-day treatment troponin I (TnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were controlled at six time points. All patients underwent conventional and tissue Doppler echocardiography prior to CY therapy (Eho 0), before cycle MEL I (Eho 1), before cycle MEL II (Eho 2), and 3 months after the completion of therapy (Eho 3). None of the patients developed clinical signs of heart failure. The peak TnI concentrations were noted at days 8, 11, and 15 during all three chemotherapy cycles. During all three cycles there was a significant increase in baseline BNP concentrations and BNP levels measured at day 1 after treatment with CY and MEL (CY: P = 0.0001, MEL I: P = 0.001, MEL II: P = 0.001). The highest BNP concentration occurred during CY treatment (0.517 +/- 0.391 microg/L). During cycles MEL I and MEL II we noted the peak BNP concentrations at day 4 following chemotherapy (MEL I 0.376 +/- 0.418 microg/L; MEL II 0.363 +/- 0.379 microg/L). During all three cycles the highest ET-1 levels occurred at day 1 after chemotherapy (CY 1.146 +/- 1.313 ng/L; MEL I 1.054 +/- 2.242 ng/L; MEL II 0.618 +/- 0.539 ng/L). A significant increase in ET-1 concentrations relative to the basal values occurred only in cycle MEL II (P = 0.003). The duration of wave a in the Doppler pulmonary vein flow increased significantly (Eho 0/Eho 1: P = 0.008, Eho 0/Eho 3: P = 0.026). There was a significant decrease in the A/a ratio in flow velocities during chemotherapy (Eho 0/Eho 1: P = 0.002, Eho 0/Eho 3: P < 0.0001). Early diastolic tissue Doppler velocities (Em) decreased significantly during individual cycles of chemotherapy (P = 0.006). A significant post-treatment increase in the incidence of mitral regurgitation was observed (Eho 0/Eho 3: P = 0.003). Treatment of MM patients with tandem autologous HSCT is cardiotoxic. Our patients did not develop clinically overt heart failure or myocardial necrosis. Increased plasma levels of BNP and ET-1 were compatible with transient neurohormonal activation of heart failure. Doppler echo

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Combined Modality Therapy; Cyclophosphamide; Echocardiography; Endothelin-1; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Natriuretic Peptide, Brain; Troponin I

We report the case of a 51-year old man with symptoms of heart failure due to severe cardiac amyloidosis, in whom treatment with melphalan and dexamethasone yielded significant improvement in clinical status and both systolic and diastolic left ventricular (LV) function over a 12-week follow-up. The improvement in LV performance was detected by Tissue Doppler (TD) and strain analysis, despite no changes in standard indices such as ejection fraction and Doppler pattern of mitral inflow. Color TD-derived myocardial velocity and deformation indices also revealed a reduction in intra-ventricular early diastolic asynchrony after therapy. In addition, an improvement in intra-ventricular systolic synchrony was detected by strain rate and strain, but not by color TD velocity imaging. These findings suggest that treatment with melphalan and dexamethasone may improve symptoms of heart failure and LV performance in subjects with cardiac amyloidosis, and that TD and particularly strain imaging could represent useful techniques to monitor the effect of therapy on LV function in the follow-up of these patients.

Topics: Amyloidosis; Dexamethasone; Drug Therapy, Combination; Echocardiography, Doppler; Heart Diseases; Humans; Male; Melphalan; Middle Aged; Ventricular Function, Left

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

A 57-yr-old woman with multiple myeloma received an autologous tandem transplant at a 4-month interval. She was conditioned twice with 225 mg/m2 melphalan. After the second transplant, interstitial pneumonitis (IP) ensued. The clinical course was life threatening and mechanical ventilation was required for 32 d. All attempts to identify an infectious agent failed. A presumptive diagnosis of idiopathic IP, possibly related to melphalan toxicity, was made. High-dose methylprednisolone administration led to rapid and durable improvement. Melphalan was employed for conditioning in the tandem setting with an interval of only 3-4 months between two courses or a dose elevation to 225 instead of 200 mg/m2, may have induced IP which responded favorably to methylprednisolone.

Topics: Anthracyclines; Female; Heart Diseases; Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases, Interstitial; Melphalan; Methylprednisolone; Middle Aged; Multiple Myeloma; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Topics: Aged; Amyloidosis; Fatal Outcome; Glucocorticoids; Heart Diseases; Humans; Male; Melphalan; Prednisolone

Median survival of patients with AL amyloidosis with clinically significant cardiac involvement is 5 months when treated with cyclic melphalan and prednisone. We investigated a regimen of continuous oral melphalan as a single agent for patients with cardiac amyloidosis who were unable to tolerate prednisone or more aggressive chemotherapy. Thirty patients with amyloid cardiomyopathy were treated with continuous oral melphalan. Seven of 13 patients, evaluable after 3-4 months of treatment, achieved a partial haematological response and three achieved a complete haematological response; six patients have survived for > 1 year. This regimen appeared to be effective in inducing haematological responses in patients who received total doses of melphalan > 300 mg.

Topics: Aged; Aged, 80 and over; Amyloidosis; Antineoplastic Agents, Alkylating; Drug Administration Schedule; Female; Heart Diseases; Humans; Male; Melphalan; Middle Aged; Survival Analysis

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Evaluation; Female; Heart Diseases; Humans; Interferon Type I; Leukocyte Count; Male; Melphalan; Middle Aged; Multiple Myeloma; Platelet Count; Prednisone

Topics: Doxorubicin; Heart Diseases; Humans; Melphalan

Topics: Adult; Amyloidosis; Antibody Formation; Antigen-Antibody Complex; Azathioprine; Chloramphenicol; Cysteine; Heart Diseases; Humans; Intestinal Obstruction; Malabsorption Syndromes; Male; Melphalan; Penicillamine; Prednisone; Time Factors; Vascular Diseases

Topics: Adult; Aged; Amyloidosis; Electrocardiography; Female; Heart Diseases; Humans; Male; Melphalan; Middle Aged