| Background: Nowadays,the most wildly used regimens for graft-versus-host disease(GvHD)prophylaxis in haploidentical peripheral blood stem cell transplantation(Haplo-PBSCT)were based on in vivo T cell depletion(TCD)with anti-thymocyte globulin(ATG)or post-transplant cyclophosphamide(PTCy).But the cumulative incidences(CIs)of a GvHD were higher than 40%.The most wildly used regimens for GvHD prophylaxis in HLA-matched unrelated donor transplantation(URD-HSCT)were usually based on ATG and the CIs of a GvHD were about24%-30%.So it is necessary to design a new GvHD prophylaxis regimen.Objective: To evaluate the efficacy and safety of low-dose ATG(5 mg/kg)combined with low-dose PTCy(50mg/kg)(low-dose ATG / PTCy)in prophylaxis of GvHD in allogeneic peripheral blood stem cell transplantation(Allo-PBSCT).Medthods: Low-dose ATG/PTCy regimen in combination with Calmodulin inhibitor and mycophenolic as GvHD prophylaxis was used for Haplo-and URD-(including 8-9/10 matched related)PBSCT.32 patients were enrolled in Haplo-and URD-PBSCT respectively.Reduced-intensity conditioning(RIC)was given to the patients above 55 years old(? 55 years),while myeloablative conditioning regimens(MACs)were for patients below 55 years old(< 55 years).The culmulative incidences of acute and chronic GvHD,immune reconstruction,relapse rate,and survival after transplantation were collected and analyzed.The results of the incidences of acute and chronic GvHD,survival after transplantation between the low dose ATG/PTCy group(31 patients)and ATG-based group(36 patients)in the Haplo-PBSCT were retrospectively compared.Results:Prospective study in Haplo-PBSCT: The CIs of grades II-IV a GvHD and grades III-IV a GvHD within days 100 post-transplant were 19.4%(95% CI,5.5-33.3%)and 6.9%(95% CI 0-16.3%).The incidence of c GvHD was 18.8%(95%CI,3.9%-33.7%).NRMwas 9.4%,The CIs of CMV 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.The one-year probability of relapse,DFS and OS was 25.1%(95% CI,7.3-42.9%),59%(95% CI,33.3%-84.7%)and 78.4%(95% CI,63%-93.8%),respectively.Retrospective analysis in Haplo-PBSCT:The CIs of grades II-IV a GvHD and the incidence of moderate to severe c GvHD within 1-year post-transplant in low dose ATG/PTCy group were significantly lower than that in standard ATG group(17.0% vs40.2% P=0.042;11.2% vs 40.1%,P = 0.029).NRM of 12.9 % at 1 year in low dose ATG/PTCy group was significantly lower than that of 36.2% in standard ATG regimen(P=0.038).There were strong trends of decreasing incidences of CMV and EBV reactivation(41.9% and 45.2%,respectively)in low dose ATG/PTCy group as compared with that(63.8% and 66.7%,respectively)in standard dose ATG group(P=0.072 for CMV reactivation,P=0.076 for EBV reactivation).The CIs of relapse at1 year were higher than standard dose ATG group(22.8% vs 8.7%,P = 0.042).The one-year probability of LFS and OS had no difference between two groups(67.0% vs59.2% P = 0.540;74.9% vs 59.4% P = 0.255)?Prospective study in URD transplantation: The CIs of grades II-IV a GvHD within days 100 post-transplant were 3.1%(0-6.2%).With a median follow-up of 6months(range 0.5-16 months),only two patients suffered from very slight skin c GvHD.NRM was 12.5%.The one-year probability of RI,DFS and OS was 21.1%(95% CI,11.1%-30.7%),78.8%(95% CI,71%-86.6%)and 86.3%(95% CI,79.9%-92.7%),respectively.Conclusion: Low-dose ATG/PTCy can effectively prevent the occurrence of acute and chronic GvHD after Haplo-and URD-(including 8-9/10 matched related)PBSCT and there is no increase in the relapse rate.Further research is needed. |
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