Haploidentical stem cell transplantation with post-transplant cyclophosphamide prophylaxis resulted in less severe acute graft-versus-host disease (GVHD) and lower rates of nonrelapse mortality when compared with matched unrelated donor transplant and standard GVHD prophylaxis, according to study results presented at the 2020 Transplantation & Cellular Therapy Meeting.
Among patients undergoing stem cell transplantation, haploidentical transplant is associated with lower rates of severe acute GVHD than matched unrelated donor transplant. The severity and characteristics of acute GVHD in these two donor sources has not been directly reported.
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Rima M. Saliba, PhD, assistant professor in the department of stem cell transplantation (research) at The University of Texas MD Anderson Cancer Center, and colleagues reviewed data from patients who contracted grade 2-4 acute GVHD after stem cell transplant from a haploidentical (n = 758) or matched unrelated (n = 2586) donor. Data regarding GVHD characteristics and nonrelapse mortality were taken from the Center for International Blood and Marrow Transplant Research database.
GVHD prophylaxis among patients with haploidentical donors included a calcineurin inhibitor, mycophenolate mofetil and post-transplant cyclophosphamide. Among patients with matched unrelated donors, prophylaxis included a calcineurin inhibitor, with mycophenolate mofetil or methotrexate.
Patients with haploidentical donors had a significantly lower rate of 6-month cumulative acute GVHD (35% vs. 45%; P < .001), as well as a lower rate of grade 3-4 acute GVHD (28% vs. 39%; P = .001).
The median time to acute GVHD after transplant was 35 days (range, 5-218) for patients with haploidentical donors and 33 days (range, 7-374) for patients with matched unrelated donors. Both groups exhibited a similar proportion of patients diagnosed with acute GVHD after day 100 post-transplant (4% vs. 6%).
Haploidentical donor status was associated with lower rates of upper gastrointestinal tract (46% vs. 53%; P = .04) and liver involvement (11% vs. 15%), though rates of lower gastrointestinal tract and skin involvement did not markedly differ.
In addition, patients with haploidentical donors experienced a lower prevalence of GVHD with two or more organs involved (26% vs. 35%; P = .008), as well as stage 4 skin (1% vs. 5%; P = .01), stage 3-4 liver involvement (4% vs. 7%; P = 0.04), or lower gastrointestinal tract involvement (14% vs 21%; P = 0.01).
Transplant from a haploidentical donor provoked lower rates of 2-year nonrelapse mortality (18% vs. 30%) and cumulative nonrelapse mortality (19% vs. 51%).
A multivariate analysis linked haploidentical donor status with significantly reduced nonrelapse mortality among sex-matched pairs only (cumulative incidence, 15% vs. 30%; P = .002). In sex-mismatched pairs, cumulative incidence was similar between haploidentical donors and matched unrelated donors (30% vs. 26%).
A further analysis of 718 patients aged 60 years or older found that haploidentical recipients (n = 92) had a lower 6-month cumulative incidence of acute GVHD (29% vs. 44%; P < .001), as well as a lower incidence of grade 3-4 GVHD (25% vs. 41%; P = .003).
In this patient subset, the median time to diagnosis was 38 days (range, 11-200) for haploidentical donor recipients and 34 days (range, 7-374) for matched unrelated donor recipients (P = .04). Although organ involvement did not significantly differ between groups, stage 4 involvement occurred less frequently among haploidentical donor recipients.
As with the overall population, a multivariate analysis showed a link between lower cumulative incidence of acute GVHD and sex-matched donor status favoring haploidentical donors (11% vs. 33%; P = .001).
