Melphalan on day -1 versus day -2 in patients with plasma cell disorders undergoing autologous stem cell transplant

Abstract

High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts ( p = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, p = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice.

Impact of melphalan day -1 vs day -2 on outcomes after autologous stem cell transplant for multiple myeloma

“…D-2 dosing was historically used to avoid potential effects of residual melphalan on the stem cell graft. Two retrospective studies of MM patients undergoing ASCT observed no difference in time to platelet and neutrophil engraftment between D-1 and D-2 melphalan dosing ( 7 – 9 ), whereas a study of 367 patients showed delays in both platelet and neutrophil engraftment with D-1 melphalan ( 10 ).…”