神田 善伸

Rapid tapering of cyclosporine (CsA) in the early phase after allogeneic transplantation may induce a potent graft-versus-leukemia/lymphoma (GVL) effect. We retrospectively reviewed the outcomes of patients with high-risk hematological malignancies who underwent their first transplantation at our institution. The blood CsA concentration was maintained at around 300 ng/ml. Our planned schedule for tapering CsA in patients without graft-versus-host disease (GVHD) or with limited GVHD was to reduce the dose by 10% per week starting from day 30 for related HSCT or from day 50 for unrelated HSCT. In total, we began tapering CsA in 36, and classified them into 2 an "On-schedule group" or "Delayed group" based on the timing of starting tapering. The cumulative incidences of grade II-IV acute GVHD overall were 33.8% and 39.4% (P = 0.746) in the On-schedule and Delayed groups. The On-schedule group showed no significant difference in non-relapse mortality, but showed a trend toward a higher relapse rate, resulting in significantly worse overall survival (55.6% vs 72.2% at 1y, P = 0.025) and worse disease-free survival (38.9% vs 66.7% at 1y, P = 0.059). These findings suggest that early CsA tapering after HSCT in high-risk patients was not effective.

We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II-IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5-10), early initiation (Days 0-4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II-IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II-IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML.

HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo) is emerging as an effective alternative due to donor availability and safety. We conducted a nationwide retrospective study comparing the outcomes of PTCy-haplo with both anti-thymocyte globulin (ATG)-free and ATG-administered matched unrelated donors (MUD) transplantation, using peripheral blood stem cells as the first transplantation for acute myeloid leukaemia (AML). Our study showed a lower and slower haematopoietic recovery and a higher incidence of infection-related deaths after PTCy-haplo than after MUD transplantation. In addition, we revealed an increased risk of acute and chronic graft-versus-host disease (GVHD) in ATG-free MUD transplantation in comparison to PTCy-haplo. For grades III-IV acute GVHD, the hazard ratio (HR) was 2.71 (95% CI, 1.46-5.01), and for extensive chronic GVHD, the HR was 3.11 (95% CI, 2.07-4.68). There was no significant difference regarding overall survival amongst the groups. In addition, GVHD-free relapse-free survival (GRFS) was lower in ATG-free MUD transplantation than in PTCy-haplo (HR, 1.46; 95% CI, 1.17-1.82). Notably, ATG-administered MUD transplantation showed no significant difference in GRFS from PTCy-haplo, negating the advantage of PTCy. Our results suggest that PTCy-haplo could be viable for AML patients without an HLA-matched related donor.

Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49-0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68-1.16], P = 0.40; NRM 0.98 [95% CI: 0.68-1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.