Clofarabine and High-Dose Melphalan Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation

Introduction Fludarabine makes up the cornerstone of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplant (alloHCT). However, during the nationwide fludarabine shortage in 2022, many institutions used fludarabine-free RIC regimens out of necessity though data is extremely limited. We report results of our experience with a clofarabine-based RIC conditioning for adult patients with non-Hodgkin lymphoma and myeloid malignancies. Methods In this retrospective matched cohort study at Stanford Health Care, we compared adult RIC alloHCT recipients receiving clofarabine and melphalan (CloMel) to a matched cohort receiving fludarabine and melphalan (FluMel) between 1/2022 to 12/2022. CloMel consisted of clofarabine 30 mg/m2 on days -6 to -2 followed by melphalan 140 mg/m2 on day -1, while FluMel consisted of fludarabine 30 mg/m2 on days -5 to -2 followed by melphalan 140 mg/m2 on day -1. Dose adjustments were made in patients with baseline renal dysfunction according to institutional guidelines. Patients received graft versus host disease (GvHD) prophylaxis with tacrolimus and methotrexate. Results We identified 9 matched pairs for a total of 18 patients, with most patients receiving alloHCT for a myeloid malignancy. All patients received a peripheral blood stem cell transplant, with 89% receiving a matched unrelated donor and 11% receiving a matched related donor. Baseline characteristics were balanced between groups. There was no difference in median time to neutrophil engraftment (14 vs 14 days; p=0.42), median time to platelet engraftment (16 vs 24 days; p=0.33), or 100% donor whole blood chimerism (71% vs 78%; p=0.32) at 6 months in the CloMel and FluMel groups, respectively. No statistically significant difference was observed for the overall incidence of acute (22% vs 0%; p=0.13) and chronic (0% vs 44%; p=0.09) GvHD at 6 months between the CloMel group compared to the FluMel group.At 6 months, 2 patients the CloMel group and no patients in the FluMel group experienced early non-relapse mortality. Both patients who died experienced acute renal failure secondary to conditioning chemotherapy with a median onset of renal dysfunction 6 days after initiation of clofarabine, followed by sepsis and multi-organ failure. Both patients required initiation of external renal replacement therapy and ultimately passed 12 days and 29 days post-transplant, prior to engraftment. Notably, both patients had a history of kidney dysfunction prior to transplant. Conclusion CloMel demonstrated similar efficacy outcomes at 6 months and represents a feasible alternative to FluMel as a RIC regimen. However, given the notable occurrence of renal failure and early death in the CloMel group, careful consideration and extra caution in administering to patients with a prior history of renal disease is warranted.