Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Significant Increase in Survival in the Post-Targeted Immunotherapy Era

Abstract

Background The management of adult acute lymphoblastic leukemia (ALL) has evolved over the last five years with the FDA approval of targeted immunotherapies, routine incorporation of minimal residual disease, and uptake of the pediatric regimen in young adults. However, allogeneic hematopoietic cell transplantation (HCT) remains an important treatment modality for this population and progress has concomitantly occurred in the field of HCT. We hypothesized that a combination of these advancements would translate into significant improvements in post-HCT survival in adult ALL. Methods Successive patients >= 18 years who had undergone first allogeneic HCT for ALL at Stanford University between January 1, 2005 and January 30, 2019 were included and were categorized as Cohort 1 or Cohort 2 based upon time period of HCT: 2005-2013 vs 2014-2019, respectively. For survival analyses, patient post-HCT follow-up times in Cohort 1 were truncated to the maximum follow-up time in Cohort 2 (approximately 5 years) in order to account for differences in long-term follow-up between the cohorts. Results 308 adults (163 in Cohort 1; 145 in Cohort 2) with ALL underwent HCT. The median follow-up from HCT was 738 and 588 days in Cohorts 1 and 2, respectively. Median age was 39 years (range, 19-70) and did not differ between groups; 50-55% were men and 30-35% were Hispanic across time periods. Most patients (79-85% across time periods) received myeloablative conditioning (MAC) with a TBI-based regimen; a slight increase in non-TBI based MAC was observed in Cohort 2. Relative to Cohort 1, patients transplanted in Cohort 2 received cord blood units more frequently and were also more likely to enter HCT in CR1. The estimated six month, one, and two-year HCT outcomes are depicted in Table 1. The 2-year cumulative incidence of relapse (31% vs 25%) and TRM (23% vs 17%) were not significantly different between the two time cohorts but trended in favor of Cohort 2. Significant improvement in OS following HCT was observed in Cohort 2 (Figure 1) with estimated 2-year OS of 51% vs 70% in Cohorts 1 and 2, respectively. Conclusions In this large single center analysis of adult ALL outcomes following HCT over time, we demonstrate that OS following HCT has substantially improved since 2014, coinciding with a number of advancements in the fields of ALL and HCT. These data, if confirmed in a multi-center analysis, should provide new benchmarks for outcomes following HCT in adult ALL.