Low Dose Anti-Thymocyte Globulin Plus Low Dose Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis in Haploidentical Peripheral Blood Stem Cell Transplantation for Patients with Hematologic Malignancies: A Prospective, Phase II Study

Background:Nowadays, the most wildly used regimens for graft-versus-host disease (GvHD) prophylaxis in haplo-hematopoietic stem cell transplantation (Haplo-HSCT) were based on in vivo T cell depletion (TCD) with anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). To improve the efficiency of GvHD prophylaxis in haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT), a novel regimen, which is composed of low dose of ATG (5 mg/kg) and low dose PTCy (50mg/kg) for GvHD prophylaxis, was evaluated in a prospective phase II clinical trial (Clinicaltrials.org NCT03395860). Method:Thirty-two patients with hematological malignancies were enrolled in this trial. Median age was 37 years (range, 20 to 62 years). At the time of transplantation, a total of fourteen patients with AML/ALL reached first or subsequent complete response (CR1, ≥CR2); the other eighteen patients had active disease including three ALL, three MDS-EB II, two CMML and ten AML patients. All patients received myeloablative conditioning regimens except for three patients. The GvHD prophylaxis contained ATG 2.5mg/kg administered on day -2 to -1 and cyclophosphamide (Cy) 50 mg/kg on day +3, cyclosporine A (CsA) and mycophenolate mofetil (MMF) initiating on day +4. The PBSC grafts for all patients were mobilized with G-CSF. Unrelated cord blood (UBC) was infused as the third party cells at 4 hours before PBSC graft infusion Results: All patients received PBSC grafts with MNCs 15.5 (7.5-28.3) ×108/kg and CD34+ cells 13.39 (2.4-31.7) ×106/kg. The median nuclear cell number and CD34+ cell number of unrelated third party cord blood were 2.1 (1.4-4.14) ×107/kg and 5.6 (1.52-11.2) ×104/kg, respectively. The median time for neutrophil and platelet engraftment was 12 days (range 9-20) and 16 days (range 12-25), respectively. Chimerism monitoring showed that all the patients were fully donor chimerism between days 14 to 28 after transplantation. There was no chimerism of cord blood cells in all patients on days 14 after transplantation. Primary graft failure occurred in one patient (3.1%).One patient with AML experienced secondary graft failure after CMV pneumonia at day 90. The cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD were 19.4% (95% CI, 5.5-33.3%) (Figure A) and 6.9% (95% CI 0-16.3%) (Figure B) by day 100, respectively. The CIs within six months of moderate-to-severe cGVHD were 18.8% (5/27 cases) (95% CI, 3.9%-33.7%)(Figure C). No patient died from acute and chronic GvHD. The one-year probability of relapse was 25.1% (95% CI, 7.3-42.9%)(Figure D). The one-year probabilities of disease free-survival (DFS) and overall survival (OS) were 59% (95% CI, 33.3%-84.7%) and 78.4% (95% CI, 63%-93.8%)(Figure E), respectively. The CIs of CMV reactivation and EBV reactivation by day 180 were 37.5% (95% CI, 19.8-55.2%) and 40.6% (95% CI, 22.6-58.6%), respectively. Non-relapse mortality (NRM) was 9.4 %. Conclusion: The results suggested that low dose ATG with low dose PTCy as GvHD prophylaxis in Haplo-PBSCT had promising activity. Disclosures No relevant conflicts of interest to declare.