melphalan and Heart-Failure

Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis and 25% of patients with amyloid transthyretin (ATTR) amyloidosis die within 24 months of diagnosis. Effective therapy exists but is ineffective if end-organ damage is severe.. To provide evidence-based recommendations that could allow clinicians to diagnose this rare set of diseases earlier and enable accurate staging and counseling about prognosis.. A comprehensive literature search was conducted by a reference librarian with publication dates from January 1, 2000, to December 31, 2019. Key search terms included amyloid, amyloidosis, nephrotic syndrome, heart failure preserved ejection fraction, and peripheral neuropathy. Exclusion criteria included case reports, non-English-language text, and case series of fewer than 10 patients. The authors independently selected and appraised relevant literature.. There was a total of 1769 studies in the final data set. Eighty-one articles were included in this review, of which 12 were randomized clinical trials of therapy that included 3074 patients, 9 were case series, and 3 were cohort studies. The incidence of AL amyloidosis is approximately 12 cases per million persons per year and there is an estimated prevalence of 30 000 to 45 000 cases in the US and European Union. The incidence of variant ATTR amyloidosis is estimated to be 0.3 cases per year per million persons with a prevalence estimate of 5.2 cases per million persons. Wild-type ATTR is estimated to have a prevalence of 155 to 191 cases per million persons. Amyloidosis should be considered in the differential diagnosis of adult nondiabetic nephrotic syndrome; heart failure with preserved ejection fraction, particularly if restrictive features are present; unexplained hepatomegaly without imaging abnormalities; peripheral neuropathy with distal sensory symptoms, such as numbness, paresthesia, and dysesthesias (although the autonomic manifestations occasionally may be the presenting feature); and monoclonal gammopathy of undetermined significance with atypical clinical features. Staging can be performed using blood testing only. Therapeutic decision-making for AL amyloidosis involves choosing between high-dose chemotherapy and stem cell transplant or bortezomib-based chemotherapy. There are 3 therapies approved by the US Food and Drug Administration for managing ATTR amyloidosis, depending on clinical phenotype.. All forms of amyloidosis are underdiagnosed. All forms now have approved therapies that have been demonstrated to improve either survival or disability and quality of life. The diagnosis should be considered in patients that have a multisystem disorder involving the heart, kidney, liver, or nervous system.

Topics: Algorithms; Benzoxazoles; Dexamethasone; Diagnosis, Differential; Gene Silencing; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Transplantation; Melphalan; Prognosis; Proteinuria; Stem Cell Transplantation

AL amyloidosis is a systemic disease characterised by pathogenetic proteins produced by malignant plasma cells and the deposition of them in different organs of the body. Amyloidogenic protein is the light chain of the monoclonal immunoglobulin, which becomes water insoluble, precipitates and deposites in the extracellular space resulting damage of organ function. AL amyloidosis belongs to plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases. Diagnosis - such as in case of other types of amyloidosis - is based on histology. Identification of the amyloidogenic protein often needs special examinations. The goal of the therapy is the eradication of the malignant cell clone. Therapeutical armamentarium has been largely flared in the past few decades, several drugs with new mechanisms of action are available (thalidomide, lenalidomide, bortezomib). The standard treatment is high dose chemotherapy followed by autologous stem cell transplantation in case of eligible patients. Transplantation uneligible patients can be treated with a low dose alkylating agent with or without dexamethasone, or with the new agents. The therapeutical decision must be preceded by very thorough risk assessment. Early diagnosis and the prompt beginning of the treatment has great significance because the evolving functional abnormalities of parenchymal organs (mainly cardiac failure) prevents the effectivity of the treatment. Amyloidosis is an orphan disease, special centers play a significant role in the field of clinical trials.

Topics: Algorithms; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Dexamethasone; Diagnosis, Differential; Heart Failure; Humans; Lenalidomide; Melphalan; Myocardium; Palliative Care; Patient Selection; Prognosis; Pyrazines; Quality of Life; Risk Assessment; Risk Factors; Stem Cell Transplantation; Thalidomide; Transplantation, Autologous

Topics: Aged; Amyloidosis; Anti-Inflammatory Agents; Dexamethasone; Diagnosis, Differential; Disease Progression; Early Diagnosis; Fatal Outcome; Female; Heart Failure; Humans; Immunosuppressive Agents; Mass Screening; Melphalan; Myeloablative Agonists; Nurse's Role; Patient Education as Topic; Pleural Effusion; Proteinuria; Rare Diseases; Stem Cell Transplantation; Thalidomide

The primary cardiac lymphoma (PCL) is an extremely infrequent tumor suffered by immunocompetent patients with a difficult diagnosis and slow progress leading to a serious prognosis and few therapeutically possibilities. It's a primary-cardiac non-Hodgkin's lymphoma (NHL) in a patient of 46-year-old, immunocompetent, who started with a congestive heart failure and atrial flutter. Some examinations were carried out such as a transesophageal echocardiography (TEE), a computed tomography (TC) and a magnetic resonance imaging (MRI) and an intracardiac tumor placed in the interauricular septum was detected. The diagnosis was based on a pleural fluid cytological examination. It was decided to follow a chemotherapy treatment and the autologous peripheral blood stem cells transplantation was carried out. The patient remains in full remission thirty-six months after diagnosis and twenty-nine months after the autotransplant. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate and aggressive antilymphoma therapy can thus help in obtaining a long survival in patients with PCL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Atrial Flutter; Carmustine; Cyclophosphamide; Cytarabine; Doxorubicin; Echocardiography, Transesophageal; Etoposide; Heart Failure; Heart Neoplasms; Heart Septum; Hematopoietic Stem Cell Transplantation; Humans; Hydrocortisone; Immunocompetence; Injections, Spinal; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Male; Melphalan; Methotrexate; Middle Aged; Pleural Effusion; Prednisone; Remission Induction; Tomography, X-Ray Computed; Transplantation Conditioning; Transplantation, Autologous; Vincristine

A 59-year-old female was admitted to Tsukuba University Hospital and diagnosed as IgA-lambda multiple myeloma (stage IIIA). No cardiovascular disorder with the exception of minor ischemic changes in ECG was revealed before treatment. Recombinant human alpha-interferon (IFN) at a dose of 3 million units combined with melphalan and prednisolone was administrated. Sixteen hours after the first administration of IFN, IFN was suspended by the symptoms of congestive heart failure (CHF). Treatment with diuretics and catecholamine products showed almost complete recovery from CHF in 3 weeks. An adverse reaction to IFN was strongly suspected as the cause of CHF.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiotonic Agents; Combined Modality Therapy; Cyclophosphamide; Diuretics; Female; Heart Failure; Humans; Immunologic Factors; Interferon Type I; Melphalan; Middle Aged; Multiple Myeloma; Plasmapheresis; Prednisolone; Recombinant Proteins; Vindesine

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

Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy.. We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation.. Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics.. As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Cyclophosphamide; Drug Administration Schedule; Female; Heart Failure; Humans; Melphalan; Middle Aged; Paclitaxel; Thiotepa

Topics: Aged; Amyloidosis; Antineoplastic Agents; Bortezomib; Cyclophosphamide; Dexamethasone; Erythema; Female; Heart Failure; Humans; Melphalan; Monoclonal Gammopathy of Undetermined Significance

Nearly half of AL amyloidosis patients have cardiac involvement, an independent predictor of poor prognosis. High-dose melphalan and autologous stem-cell transplantation (HDM/SCT) can induce complete hematologic responses and prolong survival in AL amyloidosis. Granulocyte colony-stimulating factor (G-CSF)-induced mobilization of peripheral blood stem cell (PBSC) in AL amyloidosis patients is associated with volume overload, arrhythmias and capillary leak syndrome. Plerixafor has a different mechanism of action and has non-overlapping toxicities with G-CSF. We describe our experience in five patients with AL amyloidosis and cardiac involvement who received plerixafor with G-CSF for PBSC mobilization. Median age was 56 years; two patients had undergone heart transplantation within the year prior to HDM/SCT. Three patients received plerixafor after an initial trial of mobilization with G-CSF alone. No patient had any significant toxicities during mobilization and PBSC collection. The median total yield of PBSCs collected was 5.9 × 10(6) CD34+ cells/kg; the median number of leukapheresis days was 2. Neutrophil engraftment after HDM/SCT occurred at a median of nine days, platelet engraftment at a median of 13 days. Plerixafor was effective and well tolerated when used upfront or as rescue for PBSC mobilization in AL amyloidosis patients with cardiac involvement.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Benzylamines; Cyclams; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Heterocyclic Compounds; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Remission Induction; Transplantation, Autologous

We experienced the case of a 67-year-old man with refractory heart failure. He presented with dyspnea and progressive pitting edema of the lower limbs. Diuretics were insufficient to improve his symptoms. Cardiac catheterization demonstrated pulmonary hypertension. Additional examinations confirmed polyneuropathy, organomegaly, endocrinopathy and monoclonal gammopathy. The plasma vascular endothelial growth factor (VEGF) level was 1,340 pg/mL. The patient was diagnosed with Crow-Fukase (POEMS) syndrome. Echocardiography detected left ventricular hypertrophy and diastolic dysfunction. Polysomnography demonstrated severe sleep-disordered breathing. We herein describe a case of pulmonary hypertension with Crow-Fukase syndrome accompanied by left ventricular diastolic dysfunction and sleep-disordered breathing.

Topics: Aged; Dexamethasone; Diuretics; Drug Resistance; Edema; Furosemide; Heart Failure; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Melphalan; POEMS Syndrome; Polysomnography; Prednisolone; Pulmonary Wedge Pressure; Sleep Apnea Syndromes; Thalidomide; Ultrasonography; Vascular Endothelial Growth Factor A; Ventricular Dysfunction, Left

To characterize patients with cardiac amyloidosis using echocardiography, electrocardiogram (ECG) and right heart catheterization (RHC).. Fourteen patients with biopsy verified light chain or transthyretin cardiac amyloidosis were included. All patients had heart failure with markedly elevated NT-proBNP. Echocardiography demonstrated biventricular hypertrophy, left atrial enlargement and normal to slightly reduced left ventricular ejection fraction. Tissue Doppler septal é was low and median E/é was high. Within 6 months RHC was performed in eight of the patients. The restrictive filling pattern demonstrated by echocardiography corresponded well to median pulmonary wedge pressure (21 mmHg). Systolic pulmonary artery pressure (SPAP) was increased, whereas cardiac output and stroke volume were seen to be decreased with both methods. ECG demonstrated: low voltage (36%), abnormal R-progression (65%), ST-T abnormalities (71%) and high incidence of fibrillation (36%). In addition, a case report following the treatment of melphalan and dexamethasone is presented with improvement of hypertrophy, SPAP, left ventricular mass and é.. These findings should lead to a suspicion of cardiac amyloidosis and suggest further investigation.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Cardiac Catheterization; Cardiomegaly; Dexamethasone; Echocardiography, Doppler; Electrocardiography; Female; Heart Failure; Humans; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Function, Left

Long-term survival remains poor for patients with cardiac amyloidosis. High-dose melphalan (MEL) with stem cell transplantation (HDM/SCT) is an effective treatment for AL amyloidosis, but patients with cardiac involvement are ineligible because of high therapy-related mortality. Here we report detailed HDM/SCT outcomes of 9 patients with cardiac failure. Their median age was 56 years (range, 45∼66). After a median follow-up of 15 months (range 9∼32), three died of multiorgan failure within the early phase after HDM/SCT, and the other six including poor risk patients are alive at present. Their symptoms of cardiac decompensation have improved. Decreases in interventricular septum thickness were confirmed in 4 patients 6∼12 months after HDM/SCT by echocardiography. One-year overall survival rate was 67%, longer than previously reported rates. HDM/SCT may lead to improvements in quality of life and extended survival in cardiac amyloidosis patients. Meanwhile, the median dosage of MEL in our procedure was 103 mg/m(2) (range 68∼180), less than the recommended dose, and patients were maintained on miscellaneous therapies. Further studies are required to clarify an effective MEL dose and to refine selection criteria for patients undergoing HDM/SCT.

Topics: Aged; Amyloidosis; Cardiomyopathies; Female; Heart Failure; Heart Function Tests; Humans; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Transplantation, Autologous; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Amyloidosis; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Boronic Acids; Bortezomib; Calcium Channel Blockers; Dexamethasone; Diuretics; Drug Therapy, Combination; Female; Heart Failure; Humans; Lenalidomide; Melphalan; Middle Aged; Myocardium; Prealbumin; Pyrazines; Severity of Illness Index; Stem Cell Transplantation; Thalidomide; Treatment Outcome

Patients with light chain (AL) amyloidosis who present with severe heart failure due to cardiac involvement rarely survive more than 6 months. Survival after cardiac transplantation is markedly reduced due to the progression of amyloidosis. Autologous stem-cell transplantation (ASCT) has become a common therapy for AL amyloidosis, but there is an exceedingly high treatment-related mortality in patients with heart failure.. We developed a treatment strategy of cardiac transplant followed by ASCT. Twenty-six patients were evaluated, and of 18 eligible patients, nine patients underwent cardiac transplantation. Eight of these patients subsequently received an ASCT.. Six of seven evaluable patients achieved a complete hematologic remission, and one achieved a partial remission. At a median follow-up of 56 months from cardiac transplant, five of seven patients are alive without recurrent amyloidosis. Their survival is comparable with 17,389 patients who received heart transplants for nonamyloid heart disease: 64% in nonamyloid vs. 60% in amyloid patients at 7 years (P=0.83). Seven of eight transplanted patients have had no evidence of amyloid in their cardiac allograft.. This demonstrates that cardiac transplantation followed by ASCT is feasible in selected patients with AL amyloidosis and heart failure, and that such a strategy may lead to improved overall survival.

Topics: Adult; Aged; Alanine; Amyloidosis; Aspartate Aminotransferases; Cardiotonic Agents; Female; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Stem Cell Transplantation; Stroke Volume; Transplantation, Autologous

We evaluated the capability of soluble cardiac biomarkers to predict tolerability and outcomes of IMiD-containing treatments among 106 patients treated on clinical trials. Baseline elevations in troponin T (TnT) and N-terminal brain naturietic protein (NT-proBNP) predicted for an inability to tolerate IMiD-based regimens. The best predictors for early attrition during cycle 1 were TnT ≥ 0.07 μg/L and NT-proBNP ≥ 11,939 ng/L. NT-proBNP-response underperformed TnT-response as a predictor for overall survival (OS), but both predicted for early protocol attrition. Despite hematologic response, IMiD-treated patients were at higher risk for NT-proBNP rises and early drug discontinuation than a control population but not for early death. These observations prompt two questions: (1) does IMiD-based therapy lead to increased fluid retention and/or cardiac toxicity and (2) is an NT-proBNP-driven cardiac response system valid in IMiD-treated amyloidosis patients? Recognition of potential drug-induced cardiac toxicity is important so that increased cardiac surveillance and drug dose-adjustment or discontinuation may be implemented.

Topics: Amyloid; Amyloidosis; Biomarkers; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Drug Therapy, Combination; Heart Failure; Humans; Immunoglobulin Light Chains; Immunologic Factors; Lenalidomide; Melphalan; Natriuretic Peptide, Brain; Patient Dropouts; Peptide Fragments; Stem Cell Transplantation; Thalidomide; Troponin T

A 60-year-old woman was admitted with acute heart failure and was diagnosed as having primary systemic AL amyloidosis with cardiac involvement by endomyocardial biopsy. Electrophoresis revealed an IgG-lambda monoclonal component and amyloidosis was evident in the gastric and rectal mucosa. Her cardiac function at diagnosis was poor, including an ejection fraction of 59% and IVS of 19 mm, and serum cardiac troponin T (cTnT) was elevated (0.12 ng/ml). She was treated with melphalan-dexamethasone (Mel-Dex) therapy once a month. After more than a year, cardiac function and performance status were maintained, with decreasing levels of cTnT, indicating that Mel-Dex represents a feasible and effective therapeutic option for patients with AL amyloidosis with cardiac dysfunction.

Topics: Acute Disease; Amyloidosis; Biomarkers; Dexamethasone; Female; Heart Failure; Humans; Melphalan; Middle Aged; Treatment Outcome; Troponin T

Cardiac amyloidosis (CA) is associated with a poor prognosis and a survival rate of less than 30% 2 years after clinical manifestation. Considered as a semi-malignant disease, CA is often a contraindication for HTx; however, depending on the type of CA, there are excellent treatment regimes that can be combined with HTx. In AL-amyloidosis, chemotherapy and stem cell transplantation are necessary and in TTR-amyloidosis, where the liver is the source of the pathologic protein, liver transplantation is recommended after HTx.. More than 60 patients with AL-amyloidosis and more than 25 patients with ATTR-amyloidosis have been investigated at our centre. Eighteen patients showed signs of end-stage heart failure. Four patients died within 1 month after listing for HTx. Seven patients with AL (mean age 41.8 years) and five patients with ATTR-amyloidosis (mean age 42.6 years) were successfully transplanted with an actual survival rate of 91.6%. One patient died 8 months after HTx due to infection. Five AL patients received chemotherapy and SCT and one ATTR patient was liver transplanted. Three AL patients showed complete remission of amyloidosis.. Cardiac amyloidosis is a potentially curative disease after HTx when combined with either chemotherapy and SCT or LiverTx depending on the type of the amyloidosis. Due to the natural course of the disease, urgent HTx after cardiac manifestation is mandatory. With this approach, excellent survival rates and even remission of the underlying disease is possible.

Topics: Adult; Amyloidosis; Cardiomyopathies; Decision Trees; Disease Progression; Female; Heart Failure; Heart Transplantation; Humans; Liver Transplantation; Male; Melphalan; Middle Aged; Myeloablative Agonists; Severity of Illness Index; Stem Cell Transplantation; Survival Analysis

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

Topics: Amyloidosis; Dexamethasone; Drug Therapy, Combination; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Paraproteinemias; Peripheral Nervous System Diseases; Secondary Prevention

A 63-year-old man, known to have Bechterev's disease was admitted because of weight gain and nocturnal sweating. He also had signs of heart failure with progressive exertional dyspnoea. Many months previously numerous bleedings had occurred in the skin, predominantly the face (periorbital and perioral), the inguinal region and the penis.. Extensive diagnostic test failed to find any evidence of tumor. The Rumpel-Leede tourniquet test was positive, while platelet functions was normal, suggesting vascular disease. The skin biopsy showed many perivascular amyloid deposits (AL). Immunochemical differentiation also demonstrated the same amyloid in rectal and hepatic biopsies. But there was AA amyloid in a hepatic artery. Immunophoresis indicated a biclonal gammopahty of unknown significance.. These findings indicated the diagnosis of primary AL amyloidosis associated with a gammopathy of unknown significance and a secondary AA amyloidosis in the presence of chronic Bechterev s disease. The clinical picture also showed cardiac complications, predominantly heart failure and numerous previous myocardial infarctions without S-T elevations. Echocardiography, which revealed marked thickening of the left ventricle with a restrictive filling pattern, suggested cardiac co-morbidity. The patient underwent chemotherapy with melphalan and prednisone but had a sudden cardiac death.. In a case of bleeding of unknown cause systemic amyloidosis should be considered in the differential diagnosis. A tendency towards bleeding, as in this patient, may be the first sign of amyloidosis, which ist often diagnosed quite late in the course of the disease.

Topics: Amyloidosis; Death, Sudden, Cardiac; Diagnosis, Differential; Fatal Outcome; Glucocorticoids; Heart Failure; Hemorrhagic Disorders; Humans; Male; Melphalan; Middle Aged; Myocardial Infarction; Paraproteinemias; Prednisone; Spondylitis, Ankylosing

A 47 years old woman was admitted with severe congestive heart failure. Cardiac echography showed increased intra-ventricular septum thickness, and there was a serum Ig G lambda monoclonal component. Cardiac biopsies confirmed diffuse amyloidosis of Al type. To avoid cardiac toxicity of chemotherapy, the patient received first a heart transplantation (HT), followed six months later by melphalan 200 mg/m(2) and autologous peripheral blood stem cell support (PBSCT). This case suggests that such strategy is feasible with a favorable outcome, and HT may be an appropriate procedure for some patients with Al amyloidosis who meet the criteria for PBSCT.

Topics: Amyloidosis; Fatal Outcome; Female; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Middle Aged; Transplantation, Autologous

Amyloidosis may be primary or myeloma-associated. Skeletal lesions and the percentage of bone marrow plasma cells (<10% in primary, >20% in myeloma) account for the major differences between the two varieties. In the literature there are rare cases of primary amyloidosis presenting without myeloma and followed by development of myelomatous manifestations. Usually, the primary disease (i.e. the myeloma) is advanced, when amyloidosis is diagnosed. We describe a patient who had presented with a severe and progressive systemic amyloidosis and was diagnosed later to have a mild light chain myeloma. Aggressive treatment with melphalan, prednisone and colchicine resulted in a temporary partial remission, followed by a rapid downhill course, and the patient's death. The point of relatively mild myeloma following a rapidly progressive course of advanced amyloidosis is emphasized. Awareness of the possibility of such a combination may lead to early diagnosis, a more aggressive or novel therapeutic approach and, possibly, to a better prognosis.

Topics: Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Colchicine; Disease Progression; Fatal Outcome; Female; Heart Failure; Humans; Melphalan; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Prednisone

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Female; Heart Failure; Humans; Melphalan; Middle Aged

Patients with AL amyloidosis and congestive heart failure have a very poor prognosis. To date, the recovery of these patients has not been described in detail.. To determine the frequency and characteristics regression of disease in patients with congestive heart failure due to AL amyloidosis.. Review of patients with systemic AL amyloidosis.. An international referral center for amyloidosis in the United States.. 140 patients with congestive heart failure due to Al amyloidosis who were seen between 1983 and 1994.. Functional status, Doppler echocardiography, and objective measurements of disease activity.. 3 of 140 patients (2.1%) had marked resolution of congestive heart failure and evidence for remission of disease activity. All 3 had been treated with melphalan.. Melphalan appears to have had a favorable effect in 3 patients with AL amyloidosis and heart failure. The abolition of light chains that was seen in these 3 patients suggests that light-chain toxicity may play a role in the genesis of heart failure in patients with AL amyloidosis.

Topics: Amyloidosis; Colchicine; Drug Therapy, Combination; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Melphalan; Middle Aged; Remission Induction

A 42-year-old Japanese male was admitted to our hospital because of congestive heart failure (CHF). A diagnosis of primary amyloidosis was made on the basis of a heavy deposition of amyloid in the gastric submucosal tissue in addition to the hematological and immunological findings. Intermittent chemotherapy in combination with daily oral dimethylsulfoxide (DMSO) resulted in a dramatic decrease of plasma cells in the marrow as well as a gradual improvement of CHF. With this therapy, the cardiac ejection fraction was markedly improved. This case indicates that the long-standing administration of DMSO combined with cytoreductive chemotherapy is therefore effective in treating some cases with primary amyloidosis.

Topics: Adult; Amyloidosis; Dimethyl Sulfoxide; Drug Therapy, Combination; Heart Failure; Hepatomegaly; Humans; Male; Melphalan; Prednisone

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