Impact of graft-versus-host disease on relapse and survival in adults with B-cell acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation plus post-transplant cyclophosphamide in resource-limited settings.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for B-cell acute lymphoblastic leukemia (B-cell ALL). An important mechanism for the prevention of relapse is the graft-versus-leukemia (GVL) effect, potentially at the expense of the accompanying graft-versus-host disease (GVHD), which has varying morbidity and mortality depending on its timing and grade. The association between the development of acute GVHD and chronic GVHD and a reduced incidence of relapse in B-cell ALL has been documented extensively, although conflicting results have been described in certain settings, including haploidentical HSCT followed by post-transplant cyclophosphamide (PTCy). We retrospectively examined the transplant-related outcomes of B-cell ALL adult patients undergoing HLA-matched related donor HSCT or haploidentical HSCT plus PTCy in a single center, and its association with acute and chronic GVHD. We included 43 patients with a median age of 22 years, of whom 65.1% were male. The graft source was peripheral blood stem cells in all cases. The donor source was HLA-matched related in 30.2% of cases, and haploidentical in 69.8%. Moreover, the conditioning regimen was myeloablative in 30.2% and reduced-intensity in 69.8%. Most patients underwent HSCT in first or second complete remission (44.2% each). Measurable residual disease was positive in 11.6% of patients prior to HSCT. The 2-year cumulative incidence of relapse, non-relapse mortality and overall survival (OS) were 33.3%, 7.4% and 65.5%, respectively. In a multivariable Cox-regression analysis, we found no association between acute GVHD (HR 0.94, 95% CI 0.28-3.15, p = 0.92), mild chronic GVHD (HR 0.56, 95% CI 0.06-5.23, p = 0.61) or moderate-severe chronic GVHD (HR 0.49, 95% CI 0.04-4.86, p = 0.54) and the occurrence of relapse. Also, there was no association between acute or chronic GVHD of any grade and OS. A positive MRD status showed an association with the incidence of relapse (HR 2.32, 95% CI, 0.55-9.77, p = 0.24) and OS (HR 2.17, 95% CI, 0.55-8.51, p = 0.26). In conclusion, acute and chronic GVHD were not related to differences in relapse or survival after allogeneic HSCT followed by PTCy-based GVHD prophylaxis. This underscores the importance of reappraising the role of GVHD and GVL in evolving transplant settings.