GVHD Prophylaxis With Post-transplant Cyclophosphamide and Immunosuppressants in Haplo-HSCT

By Dustin Samples - April 19, 2023

Post-transplant cyclophosphamide (PT-Cy) in conjunction with 2 immunosuppressants as graft-versus-host disease (GVHD) prophylaxis has shown relative success in patients undergoing hematopoietic stem cell transplantation (HSCT) from matched sibling donors. There are few available reports about its use in haploidentical donor transplant and in various ethnic groups. One institution looked at their own results using PT-Cy with tacrolimus and post-engraftment low-dose anti-thymocyte globulin (ATG) to address this.

At the Shanghai Institute of Hematology, Blood and Marrow Transplantation Center in Shanghai, China, researchers reported the results of 67 adult patients (aged 18-65 years) who underwent allogeneic HSCT (allo-HSCT) from haploidentical donors and received GVHD prophylaxis with PT-Cy, tacrolimus, and post-engraftment low-dose ATG. The patients had acute leukemia, chronic myelomonocytic leukemia, myeloid sarcoma, lymphoma, or high-risk myelodysplastic syndrome (MDS). All received a myeloablative or an intensified sequential conditioning regimen.

At a median follow-up of 521 days, none of the transplant recipients experienced grade III-IV acute GVHD, and only 14.9% (±4.4%) experienced grade II acute GVHD. The incidence of 2-year chronic GVHD was similarly low at 25.4±5.4% and 11.9±4% for chronic GVHD and moderate-to-severe chronic GVHD, respectively. The incidence of relapse at 2 years was 16±6.4%. The 2-year probability of disease-free survival and overall survival were 73.8% and 72.5%, and 2-year GVHD/relapse-free survival was an estimated 63.6%.

“This was the first attempt to add low-dose ATG after engraftment to the GVHD prophylaxis and the short-term outcome was satisfactory with low incidence of [acute GVHD (aGVHD)] and particularly no patient died of aGVHD,” the researchers reported.

Due to immunosuppressant use, infection was an expected risk. “We observed a relative high incidence of CMV reactivation (~50%), which was slightly lower than the GVHD prophylaxis with high-dose ATG (10 mg/kg) or at least comparable to that of protocols with moderate dose of ATG (4.5 ~ 5.0 mg/kg) combined with PT-Cy,” the authors explained. “Regarding EBV reactivation and associated PTLD, we observed a low incidence of EBV reactivation, and all these cases were clinically non-significant. The overall incidence of other events of infection was not significantly increased, compared to that of our historical control.”

Results appeared to be promising at this institution. “In conclusion, this study demonstrated that standard PT-Cy combined with tacrolimus and additional low-dose post-engraftment ATG in myeloablative Haplo allo-HSCT with PBSCs as grafts was feasible with satisfactory short-term outcomes, in terms of low incidence of aGVHD and NRM.”


Post-transplantation cyclophosphamide combined with tacrolimus and low-dose post-engraftment anti-thymoglobulin as GVHD prophylaxis for patients undergoing peripheral blood stem cell transplantation from haploidentical family donor: A single center analysis