Myeloablative Vs Reduced-Intensity Conditioning for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Among Patients over 50 Years Old Who Achieved Negative Minimal Residual Disease

Abstract

Reduced-intensity conditioning (RIC) regimen for allogeneic hematopoietic cell transplantation (HCT) has widely used in elderly patients to reduce the risk of treatment-related toxicities. Previous studies showed that RIC lead to lower non-relapse mortality (NRM), but higher relapse rate compared to myeloablative conditioning (MAC). Over the last decade, tyrosine kinase inhibitor (TKI) has dramatically improved the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) and many patients achieved negative results of minimal residual disease (MRD) at HCT. However, available data regarding the impact of conditioning intensity in patients with negative-MRD are limited. In this nationwide retrospective cohort study, we included patients over 50 years old with Ph-positive ALL who received TKI before HCT, achieved negative-MRD at HCT, and underwent their first allogeneic HCT between 2008 and 2017. Patients who received in vivo T-cell depletion or post-transplant cyclophosphamide were excluded. In this study, 90 and 136 patients received MAC and RIC regimen, respectively. MAC consisted of the vast majority of cyclophosphamide and total-body irradiation. Fludarabine and melphalan with or without low dose total-body irradiation (less than 4 Gy) were the majority of RIC regimen. The median age of patients with MAC and RIC was 54 and 60, respectively. Patient characteristics were not significantly different except for patient age and donor source between MAC and RIC groups. There were no significant differences on overall mortality, hematological relapse, and NRM, respectively (Figure). Even in multivariate analyses, RIC was not significantly associated with overall mortality (hazard ratio [HR], 1.09; 95% confidential interval [CI], 0.67-1.77; P = 0.724), hematological relapse (HR, 1.97; 95% CI, 0.75-5.15; P = 0.170), and NRM (HR, 0.84; 95% CI, 0.49-1.45; P = 0.540), respectively. Post-hoc analyses suggested that RIC resulted in the superior overall survival due to lower incidence of NRM in patients with poor performance status or high HCT comorbidity index. In conclusion, RIC is a reasonable option for patients over 50 years with negative-MRD at HCT.