melphalan and Pneumonia--Pneumocystis

From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited.

Topics: Adolescent; Bone Marrow Transplantation; Cataract; Child; Child, Preschool; Disease-Free Survival; Female; Fever; Follow-Up Studies; Gonadal Disorders; Graft Survival; Human Growth Hormone; Humans; Infant; Male; Melphalan; Mouth Mucosa; Neutrophils; Platelet Count; Pneumocystis Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Sepsis; Stomatitis; Survival Rate; Thyroxine; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

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

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bleomycin; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Deoxycytidine; Dexamethasone; Doxorubicin; Etoposide; Fatal Outcome; Gemcitabine; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases, Fungal; Male; Melphalan; Neoplasm Recurrence, Local; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Prednisone; Procarbazine; Salvage Therapy; Skin; Transplantation, Homologous; Vinblastine; Vincristine