Explorations of post-gDLI low-dose cyclophosphamide for preventing severe aGVHD

Objective: Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a serious lifethreatening complication. The granulocyte colony-stimulated factor mobilized donor lymphocyte infusions (gDLI) combined with chemotherapy is currently a commonly used treatment method. Nevertheless, gDLI may cause so severe acute graft-versus-host disease (aGVHD) as to impact prognosis. Posttransplant cyclophosphamide (PTCy) has been the backbone for GVHD prophylaxis by inducing tolerance to minor histocompatibility antigens in recipients, while the application of post-gDLI low-dose cyclophosphamide (PDCy) for GVHD prophylaxis has not yet been attempted. Methods: To explore this possibility, a retrospective study was conducted. 20 patients relapsing after HSCT were administered 20 mg/kg/d cyclophosphamide(Cy)on day 3 (for matched related transplantation) or on days 3 and 4 (for haplo-identical or unrelated transplantation) after gDLI to prevent aGVHD (the PDCy group). Furthermore, through propensity score matching, 58 matched controls received other (for HID and URD) or no (for MSD) immunosuppressive therapy for GVHD prophylaxis (the Non-Cy group). Results: With a median follow-up of 4.8 (0-37.1) months, the PDCy group had lower cumulative incidence of severe aGVHD (III-IV, 5 % vs 31 %, p = 0.02; II-IV, 25 % vs 52 %, p = 0.04), but no significant differences existed in 4-month OS (64 % vs 59 %, p = 0.51), 4-month CIR (20 % vs 47 %, p = 0.11), rates of objective response (68.8 % vs 54.5 %, p = 0.6) (hematological or extramedullary relapse), MRD complete response (25 % vs 42 % p = 1) and MRD response (25 % vs 50 %, p = 0.6) (molecular relapse) between the PDCy group and the Non-Cy group. The PDCy regimen didn't increase the incidence of adverse infection, hemorrhagic cystitis, and cardiac events. Conclusion: On the premise of safety, the PDCy regimen could effectively protest against severe aGVHD after gDLI while preserving therapeutic response rates. However, the research results still require verification through longer follow-up and large prospective randomized studies.