Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

Abstract

Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has resulted in inferior outcomes in matched sibling donor (MSD) employing peripheral blood (PB) SCTs. We hypothesized that adding thymoglobulin to PTCy would be able to control GvHD effectively. We retrospectively compared the use of standard GvHD prophylaxis encompassing a combination of PTCy and thymoglobulin (ATG) in patients with myeloid malignancies in a myeloablative conditioning MSD PBSCT. Forty-two patients underwent PBSCT using either methotrexate and cyclosporine (MTX/CSA, 21 patients) or PTCy and ATG (21 patients) as a GvHD prophylaxis. With median follow-ups of 71 months, the 1-year GvHD-free, relapse-free survival rates and chronic GvHD-free survival rate of the standard and PTCy/ATG groups were similar: 24% versus 37% ( P = 0.251) and 29% versus 43% ( P = 0.095), respectively. When focusing on chronic GvHD we observed that 17/35 patients (48.6%) suffered from this, 5/18 (27.8%) treated with MTX/CSA had extensive chronic GvHD, but 0/17 PTCy/ATG did. Twenty-one patients required additional GvHD treatment; 7/21 in the PTCy/ATG received only corticosteroid, while 8/14 MTX/CSA required at least 2 drugs. The 5-year overall survival rates were 52% and 52% ( P = 0.859), and the 5-year disease-free survival rates were 52% and 52% ( P = 0.862) for the MTX/CSA and PTCy/ATG groups, respectively. We conclude that PTCy in combination with ATG without immunosuppression of a calcineurin inhibitor can effectively control GvHD.

Should Anti-thymocyte Globulin be Added in Post-transplant Cyclophosphamide Based Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia? A Study on Behalf of the Acute Leukemia Working Party of the EBMT

“…We found that PTCY + ATG can be safely given in MUD-PBSCT without compromising engraftment and without modifying the risk of NRM when compared to PTCY-treated patients. Our findings concur with single center studies of HLA-matched PBSCT reporting reliable donor cell engraftment and low NRM rates with PTCY + ATG similar to standard CIS-treated historical controls [20][21][22][23][24]. We cannot exclude the possibility that addition of ATG to PTCY induced more viral reactivations and specific morbidity, as such information could not be captured in our retrospective analysis.…”

Should anti-thymocyte globulin be added in post-transplant cyclophosphamide based matched unrelated donor peripheral blood stem cell transplantation for acute myeloid leukemia? A study on behalf of the Acute Leukemia Working Party of the EBMT

“…Our ndings concur with single center studies of HLA-matched PBSCT reporting reliable donor cell engraftment and low NRM rates with PTCY + ATG similar to standard CIS-treated historical controls. [19][20][21][22][23] We cannot exclude the possibility that addition of ATG to PTCY induced more viral reactivations and speci c morbidity as such information could not be captured in our retrospective analysis. Nevertheless, both the incidence of NRM (any cause) and NRM due to infections did not differ between PTCY and PTCY + ATG treated patients.…”