Outcomes after Melphalan-Based Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Renal Impairment.

Abstract

Renal impairment is associated with poor outcomes following allogeneic hematopoietic cell transplantation (HCT). Although melphalan-based reduced-intensity conditioning (RIC) is demonstrated to be safe and feasible in older HCT patients, the impact of renal impairment on outcomes and toxicities following melphalan-based RIC is not well described. To evaluate how pretransplant renal function influences toxicity and survival after fludarabine/melphalan (FM) RIC and to compare measured 24-h urine creatinine clearance (UCrCl) with calculated creatinine-based renal function estimates as prognostic markers. Herein, we describe long-term outcomes of 561 HCT patients aged 55 to 74 years who received FM conditioning and tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis prior to matched donor HCT, between July 2009 and December 2019. Patients were divided based on pre-HCT UCrCl: creatinine clearance (CrCl) <90 mL/min (UCrCl 2 to 3, n = 184) and CrCl ≥90 mL/min (UCrCl 0 to 1, n = 377). CrCl for all patients was also calculated by the Cockcroft-Gault and the 2021 Chronic Kidney Disease Epidemiology Collaboration equations for comparison. UCrCl 2 to 3 correlated with higher 4-year non-relapse mortality (31% versus 19%, P < .01) and lower 4-year overall survival (55% versus 62%, P = .03) without differences in relapse rates. Neither CrCl calculation method correlated with any survival endpoint. UCrCl 2 to 3 was associated with higher severity and incidence of melphalan-related adverse events. Lower UCrCl was associated with less melphalan-induced severe GVHD- and gastrointestinal toxicity-free survival (MGTFS), a composite endpoint for severe melphalan-related morbidity and mortality at day +30 post-HCT and an early correlate of long-term survival outcomes (UCrCl 2 to 3: 18% versus UCrCl 0 to 1: 31%, P < .01). Patients with poor baseline UCrCl receiving melphalan-based RIC are at risk for significant conditioning-related toxicity and GVHD and, consequently, increased mortality. MGTFS quantified the early effect of FM RIC-related toxicities on post-HCT survival in this renally impaired HCT population.