Acute Graft-Versus-Host Disease Is Less Severe and Associated with Lower Non-Relapse Mortality after Haploidentical Transplantation with Post-Cyclophosphamide Prophylaxis

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Introduction Haploidentical (HAPLO) stem cell transplantation (SCT) has been shown to be associated with lower incidence of severe acute graft-versus-host (aGVHD) compared with 8/8 HLA-matched unrelated donor (MUD) SCT. However, no information is available regarding aGVHD characteristics comparing these 2 donor sources. Methods We aimed to compare aGVHD characteristics and non-relapse mortality (NRM) in adult patients with grade 2-4 aGVHD after HAPLO (N=758) or MUD (N=2586) SCT that were reported to the Center for International Blood and Marrow Transplant Research (Table 1). GVHD prophylaxis included a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and post-transplant cyclophosphamide (PTCy) in HAPLOs, and CNI with MMF or methotrexate in MUDs. Results The 6-m cumulative incidence (CumInc) of grade 2-4 aGVHD (35 vs 45%, 2 organs involved, stage 4 skin (1 vs 5%, p=0.01), and stage 3-4 liver (4 vs 7%, p=0.04) or LGI (14% vs 21%, p=0.01). The 2-yrs and overall CumInc of NRM since aGVHD was 18% (95% CI 14-23) and 19% (95% CI 14-24) in HAPLOs; and 30% (95% CI 27-33) and 51% (95% CI 30-68) in MUDs. In multivariate analysis, grade 2-4 aGVHD in HAPLOs was associated with significantly lower NRM, but this effect was limited to donor-recipient pairs [CumInc: 15 vs 30%, HR=0.5, p=0.002] that were not sex-mismatched (female to male). In sex-mismatched pairs [CumInc: 30% vs 26%, HR=1.2, p=0.6], NRM was comparable between HAPLOs and MUDs. Subset analyses in recipients (N=718) ≥60 years also showed HAPLOs (N=92) to have a lower 6-m CumInc of grade 2-4 (29 vs 44%, p Conclusions Compared with 8/8 HLA-matched unrelated SCT with standard GVHD prophylaxis, aGVHD tends to be less severe and associated with lower NRM after HAPLO SCT with PTCy GVHD prophylaxis. This effect is more pronounced in recipients ≥60 years of age.