Large-scale studies have demonstrated that increasing donor age is correlated with worse outcomes after hematopoietic cell transplantation (HCT). In two recently published studies in Blood Advances and The American Journal of Hematology, researchers from University of Texas MD Anderson Cancer Center have found that HCT performed with younger haploidentical donors (age < 35 years) using PTCy was associated with improved overall survival (OS) compared with HCT using older HLA-matched unrelated donors (MUDs). The first, which evaluated registry data on patients with acute lymphoblastic leukemia, found that although the risk of relapse was higher in the MUD group with conventional graft-versus-host disease (GVHD) prophylaxis, there was an approximately 2-fold increase in chronic GVHD (cGvHD), 2.75-fold increased risk of non-relapse mortality (NRM), and an overall 77% higher risk of all-cause mortality in the older group. The second study, which was a retrospective analysis in patients with AML and myelodysplastic syndrome (MDS) who underwent HCT with either a younger haploidentical or older MUD donor, further supported the use of younger haploidentical donors with PTCy over older MUDs with conventional prophylaxis.

In the first study, the authors sought to explore whether a younger haploidentical donor (PTCy prophylaxis) may be associated with better OS compared with an older MUD (conventional prophylaxis) in ALL. A total of 419 patients were included, with 232 in the older MUD cohort (median donor age of 42.4 years [IQR 38.4–46.3]) and 187 in the younger haploidentical cohort (median donor age of 25.5 years [IQR 21.3–30]). The cumulative incidence of grade II-IV aGVHD at day 100 was 21.5 (95% CI 15.0–28.7) in the older vs 16.3 (95% CI 10.9–22.7) in the younger group.  Comparing between the older and younger group, the cumulative incidence of cGVHD at 2 years was 54.4% (95% CI 47.5–60.8) vs 31.5% (95% CI 24.8–38.4) and NRM at 4 years was 35.2% (95% CI 28.5–42.0) vs 22.4% (95% CI 21.0–23.9), respectively. Conversely, the cumulative incidence of relapse at 4 years was 24.1% (95% CI 18.5–30.2) in the older and 41.7% (95% CI 32.8 - 50.3) in the younger group.

The second study evaluated outcomes among patients with AML/MDS who underwent HCT with younger haploidentical donors with PTCy prophylaxis (n = 494) or older MUDs with conventional GVHD prophylaxis (n = 1005). The younger donor group was associated with lower rates of grade II-IV acute GVHD (HR 0.64, 95% CI 0.53–0.77, p < .001), grade III-IV aGVHD (HR 0.37, 95% CI 0.25–0.53, p < .001), and cGVHD (HR 0.49, 95% CI 0.40–0.60, p < .001). The younger group also showed improved OS (HR 0.81, 95% confidence interval [CI] 0.69–0.95, p = .01) and, similar to the first study, relapse rates were higher in patients of the younger haploidentical group who received reduced intensity conditioning (HR 1.49, 95%CI 1.18–1.88, p = .001)

Overall, these retrospective findings suggest that, despite a higher risk of relapse, a younger haploidentical (PTCy-prophylaxis) donor may be preferred over an older MUD (conventional GVHD prophylaxis) donor in patients where a younger MUD is not available.  

References:

Mehta RS, Marin DC, Alousi A, et al. Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type [published online ahead of print, 2023 Jan 11]. Blood Adv. 2023;bloodadvances.2022009240. http://doi.org/10.1182/bloodadvances.2022009240

Marcoux C, Marin D, Ramdial J, et al. Younger haploidentical donor versus older matched unrelated donor for patients with AML/MDS [published online ahead of print, 2023 Feb 2]. Am J Hematol. 2023;10.1002/ajh.26870. http://doi.org/10.1002/ajh.2687

Tags: GVHD, Research, aGVHD, PTCy, donor, chronic GVHD, graft-versus-host disease, survival rate, graft-versus-host