Evidence into Practice: Changes in Haploidentical Versus Umbilical Cord Blood Graft Utilization for Hematopoietic Cell Transplantation in the U.S. in Relation to a Pivotal Randomized Clinical Trial

Abstract

Introduction

Umbilical cord blood (UCB) and haploidentical (haplo) relatives are donor sources for hematopoietic cell transplant (HCT) patients who do not have a fully matched donor. The BMT-CTN-1101 trial (2012-2018) compared outcomes of double UCB and haplo bone marrow (BM) transplants after reduced intensity conditioning. The trial showed a similar two-year progression-free survival but a lower two-year overall survival after UCB compared to haplo.

Objectives

Here, we quantified the change in graft utilization in the U.S. after the trial's publication.

Methods

11,190 HCT patients 18-70 years of age who received either UCB (single or double units) or haplo transplants (BM or peripheral blood stem cells), for leukemia, lymphoma, myelodysplastic syndrome, myeloproliferative neoplasm, were analyzed by 3 time periods: 2010-2012 (pre-study), 2013-2018 (during study), and 2019-2022 (post-study). We also expanded our analyses to a cohort of 61,880 patients to include patients who received MUD, mMUD, and HLA-matched and 1-antigen mismatched related donor transplants to assess the growth in all donor sources.

Results

There was a practice change with an increase in haplo versus UCB transplants (number of haplo transplants on average per year, pre-study: 153, during-study: 561, post-study: 1,098; 32%, 68%, 91% haplo of the total haplo and UCB transplants for pre-, during- and post-period, respectively) (Fig. 1). Increased haplo utilization began in 2013 during the CTN-1101 study and further accelerated post-study (odds ratio (OR) of 4.6 and 20.8 during-study and post-study compared to pre-study, respectively, p<0.001; OR of 4.5 post-study compared to during-study, p<0.001). Compared to non-Hispanic White (NHW) patients, Black patients were more likely to receive haplo (OR=1.74, p<0.001), and Asian patients were less likely to receive haplo (OR=0.75, p=0.002). Latinx patients received haplo similarly to NHW patients (OR=1.03, p=0.665). In expanded analyses of the 61,880 patients, transplants from all graft sources increased (the number of transplants of any graft on average per year was: pre-study: NHW: 3191, Black: 242, Latinx: 380, Asian: 141; during-study: NHW: 3597, Black: 304, Latinx: 525, Asian: 187; post-study: NHW: 3585, Black: 362, Latinx: 701, Asian: 236), particularly from mismatched grafts (mMUD, mMRD, haplo, UCB) for all racial/ethnic groups (Fig. 2).

Conclusions

Practice change toward haplo graft utilization had begun before the CTN-1101 trial's publication and continued to significantly increase after its publication, suggesting an important impact of the randomized trial. Collectively, utilization of all graft sources increased over time, particularly from mismatched grafts for patients of diverse race/ethnicity. The CTN 1101 and subsequent studies have allowed patients of diverse race/ethnicity to have increased access to a potentially curative HCT.