Younger donor age in haploidentical hematopoietic cell transplantation (HCT) with posttransplant cyclophosphamide (PTCy) for graft vs host disease (GVHD) prophylaxis was associated with improved overall survival (OS) compared with older donor age in HLA-matched unrelated donor (MUD) HCT with conventional prophylaxis in patients with acute lymphoblastic leukemia (ALL), according to research published in Blood Advances.
Researchers investigated the impact of donor age and donor type on OS, as the primary outcome of interest, in adult patients with ALL using a previously published dataset of donors and patients from the Center for International Blood and Marrow Transplant Research (CIBMTR). Secondary outcomes included grade 2 to 4 acute GVHD (aGVHD), grade 3 to 4 aGVHD, chronic GVHD (cGVHD), relapse, and nonrelapse mortality (NRM).
An initial multivariate analysis of the entire cohort by donor age (younger than 35 years, n=868 vs at least 35 years, n=418) and donor type (haploidentical, n=373, vs MUD, n=913) revealed that older donor age, but not donor type, was independently associated with poorer OS (hazard ratio [HR], 1.29; 95% CI, 1.01-1.66; P =.043).
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The researchers then directly compared outcomes in a cohort of 419 patients, with 187 in the younger haploidentical donor group and 232 in the older MUD group. More patients in the haploidentical donor group than the MUD group had B-cell immunophenotype (89% vs 77%; P <.001), received bone marrow graft (42% vs 16%; P <.001), and had reduced-intensity conditioning (45% vs 23%; P <.001).
In a multivariate analysis of this cohort, they showed the older MUD group (compared with the younger haploidentical donor group) had a significantly higher risk of chronic GVHD (HR, 1.91; 95% CI, 1.28-2.85; P =.002), higher NRM (HR, 2.75; 95% CI, 1.51-4.99; P =.001), lower relapse (HR, 0.50; 95% CI, 0.31-0.82; P =.006), and poorer OS (HR, 1.77; 95% CI, 1.16-2.71; P =.008).
“Among adult patients with ALL in CR, our data suggest that despite a higher risk of relapse, a younger haploidentical donor (age <35 years) with PTCy prophylaxis may be preferred over an older MUD (≥35 years) with conventional GVHD prophylaxis in patients for whom a younger MUD is not available. This recommendation is based on a significantly lower risk of cGVHD, lower NRM, and improved OS with a younger haploidentical donor,” the study authors explained in their report.
Limitations of the study included variability in the groups in conditioning intensity, graft type, and immunophenotype and lack of data on HLA-DPB1 matching in the MUD group. There were also limitations regarding individual HLA allele mismatches in the haploidentical group, donor parity and natural killer cell killer immunoglobulin-like receptors, and some prognostic factors.
Reference
Mehta RS, Marin D, Alousi A, et al. Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type. Blood Adv. 2023;7(8):1594-1603. doi:10.1182/bloodadvances.2022009240
