Abstract
Chronic graft-versus-host-disease (cGVHD) is a relevant cause of late morbidity and mortality related to allogenic-stem-cell transplantation in long-term survivors. GVHD prophylaxis using post-transplantation cyclophosphamide (PTCy) has improved haploidentical stem-cell transplantation (haplo-HSCT) outcomes; however, data related to characteristics, risk factors, or cGVHD outcomes are limited. In this study, we analyze the incidence, risk factors and disability related to cGVHD in patients undergoing haplo-HSCT PTCy. Retrospective multicenter analysis of 389 consecutive patients that underwent haplo-HSCT-PTCy at 7 Spanish transplant centers from 2007 to 2020. cGVHD diagnosis was made following the NIH criteria and Disability related to cGVHD was defined as Fatobene et al criteria. Median age was 48 years (5-74), and 62% were males. AML and HL were the most common indications for transplantation (37%, 22%). 36% received a previous transplant. The median follow-up was 35 months (3-102). Cumulative incidence of aGVHD and aGVHD III-IV at day +180 was 66% and 20%. The 2-year OS was 59%, 2-year PFS 54%, 2 year-GRFS was 45%. 95 patients developed cGVHD, cumulative incidence of cGVHD and cGVHD moderate-severe was 34% and 10% at 3 years. 42 patients required systemic treatment. In the univariate analysis of risk factors for cGVHD in patients alive on day +100, female donor (p=0.034), female donor and male recipient (p=0.041), DRI low (p=0.026), myeloablative conditioning (p=0-047), previous aGVHD (p=0.014), and the use of radiotherapy in conditioning (p=0.004) were identified. Busulfan conditioning was identified as a protective factor (p=0.036). In multivariate analysis, the presence of previous GVHD (p=0.031) and the protective power of conditioning with busulfan (p=0.036) remains statistically significant. cGVHD according to NIH at 3 years, moderate cGVHD showed a higher OS (p=0.054), higher PFS (p=0.004) and lower relapse than the rest of the groups (p=0.035). Receiving one line of treatment (p=0.043) and use of bone marrow were the only risk factors identified for these patients. Haplo-HPT with Cy-post shows a low, but not negligible incidence of cGVHD, and its use represents an alternative for some patients. The development of moderate cGVHD is a protective factor in this transplant modality. The characterization of predictive factors of this subgroup is relevant given the results.
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