melphalan and Renal-Insufficiency--Chronic

In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th Allogeneic Stem Cell Transplantation Clinical Practices Harmonization Workshop Series. Our work group focused on chemotherapy drug dose adaptation for hematopoietic stem cell transplantation patients presenting a comorbidity. The purpose of this workshop was to provide recommendations on chemotherapy drug dose adaptation for patient populations receiving hematopoietic stem cell transplantation who also had the following comorbidities: obesity, chronic kidney disease and hepatopathy.

Topics: Adult; Age Factors; Busulfan; Child; Comorbidity; Cyclophosphamide; Etoposide; France; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Liver Diseases; Melphalan; Obesity; Renal Insufficiency, Chronic; Societies, Medical; Surveys and Questionnaires; Thiotepa; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

High-dose melphalan 140 mg/m2 is the standard of care for patients with multiple myeloma (MM) with renal insufficiency (RI). Palifermin as a cytoprotective agent has demonstrated efficacy in reducing the intensity and duration of oral mucositis (OM) in patients who receive intensive chemotherapy/radiotherapy. There is no prospective data on the use of palifermin in patients with MM with RI.. creatinine clearance ≤60 mL/minute/1.73 m2, age >18 years, no dialysis, no active OM, and a suitable candidate for autologous stem cell transplant (ASCT). Melphalan dose ranged from 140 to 200 mg/m2 and escalated at the increment of 20 mg/m2. Six dosages of palifermin 60 mcg/kg/day were given intravenously between day -5 to day +3. Dose escalations were to stop if dose-limiting toxicities (DLTs) occurred at melphalan dose in ≥2 of 3 patients, with that dose declared as the maximal administered dose and the level below where ≤1 of 6 patients had DLTs was considered the maximally tolerated dose (MTD). Nineteen patients were enrolled from June 2007 to June 2011. Data on 15 evaluable patients is reported as 4 patients were removed. Median age was 59 years (range, 36-67 years). The overall incidence of OM ≥ grade 3 was 53% (8 of 15) and a median duration of ≥grade 3 OM was 6.5 days (range, 3-42 days). One patient in L2 (melphalan 160 mg/m2) developed atrial fibrillation on day +9. Two patients in L4 (melphalan 200 mg/m2) developed grade 4 OM, hence reaching DLT. No DLT was observed in 6 patients enrolled in L3 (melphalan 180 mg/m2). Palifermin has permitted safe dose escalation of melphalan up to 180 mg/m(2) in patients with RI.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Creatinine; Cytoprotection; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibroblast Growth Factor 7; Hematopoietic Stem Cell Transplantation; Humans; Injections, Intravenous; Male; Melphalan; Middle Aged; Multiple Myeloma; Renal Insufficiency, Chronic; Stomatitis; Transplantation Conditioning; Transplantation, Autologous