melphalan and Atrial-Fibrillation

With the eventual goal of reducing relapse and thus improving overall survival in selected lymphoma patients, a Phase I study was performed using the cytoprotectant amifostine to permit safe dose-augmentation of melphalan in the carmustine (BCNU), etoposide, cytarabine (arabinosylcytosine), and melphalan (BEAM) regimen before autologous hematopoietic stem cell transplantation. Between 30 July 2003 and 25 November 2008, a total of 32 lymphoma patients were entered, of which 28 were evaluable. We found the melphalan dose in BEAM could be safely escalated to at least 260 mg/m², a substantial increase from the usual dose of 140 mg/m² in BEAM while the trial was terminated early due to poor accrual, no maximal tolerated dose or dose-limiting toxicity was found. A Phase II trial is planned.

Topics: Adult; Aged; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Carmustine; Combined Modality Therapy; Cytarabine; Cytoprotection; Dose-Response Relationship, Drug; Etoposide; Female; Humans; Lymphoma; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Mucositis; Pancytopenia; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Transplantation Conditioning; Transplantation, Autologous; Young Adult

Amyloid light chain (AL) amyloidosis is a rare hematologic disease that may involve multiple organs. Amongst the organs, cardiac involvement causes the greatest concern as its treatment is challenging. Diastolic dysfunction rapidly progresses to decompensated heart failure, pulseless electrical activity, and atrial standstill due to electro-mechanical dissociation resulting in death. High-dose melphalan plus autologous stem cell transplantation (HDM-ASCT) is the most radical treatment but its risk is very high and thus only less than 20% of patients can receive this therapy under criteria that can suppress treatment-related mortality. In substantial proportion of patients, levels of M protein remain elevated, and organ response cannot be achieved. Moreover, relapse may occur, making prediction of treatment response and judgement of disease eradication very difficult. Herein we report a case of AL amyloidosis who was treated with HDM-ASCT, resulting in preserved cardiac function and resolution of proteinuria for more than 17 years after HDM-ASCT ensuing atrial fibrillation and complete atrioventricular block required management by catheter ablation and pacemaker implantation 10 years and 12 years after transplantation, respectively.

Topics: Amyloidosis; Atrial Fibrillation; Atrioventricular Block; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Neoplasm Recurrence, Local; Transplantation, Autologous

Topics: Adult; Aged; Atrial Fibrillation; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Incidence; Male; Melphalan; Middle Aged; Stem Cell Transplantation

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

For treatment of metastatic lung lesions there was used the method of isolated chemoperfusion in combination with metastasectomy. The study included 74 patients (mean age 43 ± 13.4 years). There were performed 99 normothermic isolated chemoperfusions of the lung: with melphalan (39) and cisplatin (60). During surgery there were no lethality outcomes. In the immediate postoperative period it was recorded 1 (1.4%) death developed in 3 days after surgery. The cause of this death was postperfusion lung edema accompanied by increase of signs of respiratory insufficiency. There were following complications after isolated chemoperfusions of the lung: anemia--23 (23.1%), nausea--13 (13.1%), vomiting--5 (5.1%), atrial fibrillation--10 (10.1%), pneumonia-2 (2.0%), pulmonary infarction--2 (2.0%), chylothorax--1 (1.0%), pneumothorax--29 (29.3%), emphysema of soft tissues of the chest wall 73 (73.7% ). Thus isolated chemoperfusion of the lung with melphalan or cisplatin is a procedure reproducible and relatively safe.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Chemotherapy, Cancer, Regional Perfusion; Chylothorax; Cisplatin; Female; Humans; Lung Neoplasms; Male; Melphalan; Metastasectomy; Middle Aged; Nausea; Pneumothorax; Respiratory Insufficiency; Subcutaneous Emphysema; Treatment Outcome

Cardiotoxicity of aggressive chemotherapeutic regimens includes cardiomyopathy and arrhythmias. Although cardiomyopathy is a well-recognized entity, arrhythmias are poorly studied.. Certain chemotherapeutic regimes are associated with supraventricular arrhythmias, particularly atrial fibrillation.. We retrospectively reviewed the data on patients who received hematopoietic stem cell transplant (bone marrow transplant; BMT) from 1998 to 2005 and developed supraventricular tachycardia (SVT) during the same hospital admission. The Fisher χ2 test and the Student t test were used for comparison of categorical and continuous variables, respectively.. During the period of 1998-2005, there were 1221 BMTs, 62 (5.1%) of which were complicated by SVT. Melphalan-based regimens demonstrated a significantly higher rate of SVT than any other chemotherapy. Out of 438 patients who received melphalan, 48 (11%) developed atrial fibrillation (n = 35) or SVT (n = 13) during the same hospital admission, and 390 did not. Patients with SVT were older, had higher baseline creatinine, larger size of the left atrium, and more cardiac comorbidities. Incidence of SVT was associated with greater length of stay (24.9 ± 8.9 d vs 19.6 ± 5.8 days, P<0.0001), even after adjustment for comorbidities.. Supraventricular tachycardia, mostly atrial fibrillation, complicates about 5% of chemotherapeutic treatments used with BMT. Melphalan is the most arrhythmogenic agent, and is associated with SVT in 11% of patients. Development of SVT results in about a 4-day increase in the length of hospital stay.

Topics: Adult; Atrial Fibrillation; Chi-Square Distribution; Female; Florida; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Length of Stay; Linear Models; Male; Melphalan; Middle Aged; Myeloablative Agonists; Retrospective Studies; Risk Assessment; Risk Factors; Tachycardia, Supraventricular; Time Factors

Twenty-seven patients with advanced multiple myeloma received high-dose therapy with 220 mg/m2 i.v. melphalan (HDM220) followed by autologous stem cell transplantation. At the time of HDM220, nine patients had primary refractory disease and 18 were in relapse after having responded to prior high-dose therapy. No toxic deaths were observed. The major adverse side-effect was grade 4 mucositis in 63% of patients. Two patients experienced reversible paroxysmal atrial fibrillation after HDM220. For the whole group of patients, the actuarial 3-year overall survival (OS) and event-free survival (EFS) are 36.1 and 16.9%, respectively. The probability of OS and EFS was significantly lower in patients treated for refractory relapse (22.9 and 0% at 2 years, respectively) as compared to primary refractory patients (66.7 and 64.3% at 2 years, respectively) or patients treated for chemosensitive relapse (42.9% at 2 years) (P = 0.0001). Low beta2-microglobulin and CRP levels at the time of HDM220 were associated with a better OS and EFS. Our data suggest that HDM220 followed by ASCT should be considered in patients with primary refractory disease or chemosensitive disease relapsing after prior intensive therapy.

Topics: Aged; Antineoplastic Agents, Alkylating; Atrial Fibrillation; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mucous Membrane; Multiple Myeloma; Pilot Projects; Recurrence; Transplantation Conditioning; Transplantation, Autologous

Among the drugs used in conditioning regimens for stem cell transplantation, high-dose melphalan (HDM) plays an important role for both its strong myeloablative effect and for its favourable dose-response ratio. Here we report five cases of high frequency atrial fibrillation (AF) developing after HDM. Duration of the arrhythmia was always very short, beginning at variable intervals after the administration of HDM, in the absence of other factors potentially able to trigger AF. In all patients sinus rhythm was restored within 72 h and the follow-up did not show any cardiac damage. To the best of our knowledge, this side-effect has never been reported to occur after HDM.

Topics: Antineoplastic Agents, Alkylating; Atrial Fibrillation; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Transplantation Conditioning; Transplantation, Autologous