Ivan S. Moiseev, Elena V. Morozova, Yulia Yu. Vlasova, Yulia V. Rudnizkaya, Elena I. Darskaya, Olga A. Slesarchuk, Sergey N. Bondarenko, Boris V. Afanasyev
R. M. Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Chair of Hematology, Transfusiology and Transplantology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation
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Cellular Therapy and Transplantation (CTT)
Volume 6, Number 3
Post-transplanation cyclophosphamide (PTCy) is a graftversus-host disease prophylaxis with rising popularity in haploidentical, related and unrelated hematopoietic stem cell transplantation (HSCT). Nonetheless, there are still concerns about graft failure and increased incidence of relapse after this type of prophylaxis. A randomized trial was initiated comparing standard-of-care rabbit ATG with PTCy-based GVHD prophylaxis in the population of chronic myeloproliferative neoplasms (CMN) and myelodysplastic syndrome (MDS) patients, who have significant risk of graft failures and relpse after HSCT.
Patients and methods
The study enrolled patients with CMN and MDS, with available unrelated donor, only 10/10-HLA matched, peripheral blood stem cells as graft source, and without severe organ dysfunction. All patients received conditioning with oral busulfan 10 mg/kg and fludarabine 180 mg/m2, and GVHD prophylaxis with tacrolimus adjusted for 5-15 ng/ml concentration and 30 days of 30 mg/kg mycophenolate mofetil. The third GVHD prophylaxis agent was either PTCy 50 mg/kg day+3,+4, or rabbit ATG (Thymoglobulin) 5 mg/kg. The strata for randomization was Seattle pretransplant assessment of mortality (PAM) index (Au BK et al., 2015). The primary endpoint was incidence of graft failure and secondary endpoints were GVHD and survival. The trial was registered on clinicaltrials.gov, NCT02627573. 24 patients were enrolled, 12 with MDS, and 12 with MPN.
Median follow-up was 9 months (range 3-28). The incidence of primary graft failure was 13% vs 25% in the PTCy and ATG groups (p=0.48). Engraftment was slower in the PTCy group (20 days vs 15 days, p=0.008). Acute GVHD grade II developed in 1 patient in each group. With current follow up and group size no cases of moderate and severe chronic GVHD were documented. One patient in each of the groups relapsed (p=0.60). Non-relapse mortality was 6% vs 50% (p=0,009) in PTCy and ATG groups, respectively. Overall survival was 94% vs 38% (p=0.003).
There is currently no difference in the incidence of primary graft failure. Significantly higher survival was observed in the PTCy group due to low non-relapse mortality. However, the follow-up time and patient numbers are small to draw definitive conclusions.
Myeloproliferative disorders, hematopoietic stem cell transplantation, GVHD prophylaxis, post-transplant cyclophosphamide, antithymocyte globulin.