Feasibility of early tacrolimus initiation in haploidentical-PBSCT with post-transplant cyclophosphamide after melphalan-based conditioning regimen.

In haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide (PTCy-haplo), early initiation of calcineurin inhibitors may affect transplant outcome by inducing CD8 transient exhaustion-like T cells which are important for chronic graft-versus-host disease and graft-versus-leukemia/lymphoma effects based on a murine model. However, to our best knowledge, there has been no report about modification of fludarabine (Flu)/melphalan (Mel)-based PTCy-haplo in a real-world setting. To evaluate the impact of early tacrolimus (TAC) initiation on outcomes, we retrospectively analyzed 19 patients at our institution between April 2017 and March 2024. The incidence and grade of cytokine release syndrome (CRS) were low (31.6% and all grades ≤ 2). In addition, despite the poor baseline characteristics including older age (median, 59 years [range, 25-72]), active diseases at the time of PTCy-haplo (n=8), and short interval between the first and second allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n=8; median, 12.4 months [range, 3.9-32.9]; all patients received Flu/busulfan (Bu)-based conditioning regimen for their first allo-HSCT), only two patients (10.5%) developed sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). With a median follow-up of 30.2 months (range, 1.0-53.1), overall survival and disease-free at 2 years were 56.8 and 51.5%, respectively. These findings suggested that early TAC initiation using Flu/Mel-based PTCy-haplo may be potentially useful for older patients with low tolerance to CRS, high risk of SOS/VOD or recurrence, or for those who are unlikely to receive Bu-based conditioning regimen due to early relapse after allo-HSCT with Bu-based conditioning regimen.