What should be the optimal dose of post-transplantation cyclophosphamide for GVHD prophylaxis in allogeneic stem cell transplantation?

Abstract

Objectives: In this study, we aimed to compare the engraftment days, graft versus host disease (GVHD) development, relapse and overall survival (OS) rates in patients using variable intensity conditioning regimens with two different post-transplant cyclophosphamide (PTCy) doses for hematological malignancies.

Material and methods: We retrospectively analyzed 162 patients who have had PTCy at a dose of 25 mg/kg × 2 and 50 mg/kg × 2 between 2018 and 2024. Patients were divided in 2 groups; PTCy dose with 25 mg/kg × 2 (Group 1, n = 45) and PTCy dose with 50 mg/kg × 2 (Group 2, n = 117). The engraftment days, GVHD, relapse and OS rates were compared across groups.

Results: All patients had myeloablative conditioning regimens and peripheral stem cell collected transplantation. 61.1 % of patients (n = 99) were alive at the end of the study (60 % (n = 27) in Group1 and 61.5 % (n = 72) in Group 2). In Group 1 the median follow-up was 6.9 months and in Group 2 this was 7 months; the median OS was 15.5 months in Group 1 and 49.5 months in Group 2 but this is not statistically significant (Log rank = 0.796). In Group 1, the engraftment times for platelets was 13 days, for neutrophils 17 days; in Group 2, for platelet this was 18 days; and for neutrophils 17 days; this was statistically significant for platelets but not for neutrophil engraftment (p: < 0.001 and p:0.839, respectively). Eighteen patients (40 %) in Group 1 and twenty-seven (23 %) patients in group 2 had acute GVHD (aGVHD). In Group 1 aGVHD rates were higher than Group 2 (p = 0.031). Seven patients (15.5 %) in Group 1 and 6 (5.12 %) patients in group 2 had chronic GVHD (cGVHD). In Group 1 cGVHD rates were also higher than Group 2 (p = 0.048). Twenty-five patients (55.6 %) in Group 1 and 19 patients (16.2 %) in Group 2 had relapsed disease (p < 0.001).

Conclusion: Our study showed that there were no differences in survival across the groups. The platelet engraftment time was shorter for the PTCy 25 mg/kg × 2 doses compared to the post-transplantation 50 mg/kg × 2 doses. Both aGVHD and cGVHD rates were higher in 25 mg/kg × 2 dose treated patients. Relapses occurred more commonly with 25 mg/kg × 2 PTCy dose.

Keywords: Hematologic neoplasms; Hematopoietic stem cell transplantation; Posttransplant cyclophosphamide.