We conducted a retrospective analysis of 157 patients who underwent haplo-HCT with in vivo dual T cell depletion as GVHD prophylaxis for various hematological disorders. We aimed to evaluate overall survival, engraftment, early toxicities, acute and chronic graft versus host disease. This is to our knowledge, the largest cohort with these characteristics that has been described in the literature. The major finding of our study is the feasibility and safety of performing haploHCT with PBSC and dual T cell depletion, resulting in acceptable OS, NRM and RFS. We did not find a difference in outcomes between recipients of MAC and RIC, this finding has been recently reported by our group (25). Older age and high risk DRI remain predictors of worse OS and NRM.
Our results show to be comparable to the ones reported by other groups. Barkhordar et al. reported their results on 92 patients undergoing haploHCT with dual T cell depletion, their results are like ours with OS of 54% for recipients of haploidentical allografts. Their rates of grades II-IV and III-IV aGVHD was 27.17% and 8.7% respectively and comparable to our results. Our group’s reported incidence of grades II-IV and III-IV aGVHD of 26% and 9.5% are comparable.(10)
The Acute Leukemia Working Party of the EBMT reported the outcomes of 67 patients who received allografts and a combination of cyclophosphamide and ATG. (26) OS was 58% (95% CI of 42–71), and incidence of grades II-IV and III-IV aGVHD at 6 months was 30% and 11% respectively. The lower incidence of cGVHD has been extensively reported with the use of ATG, especially with the use of PBSC as a graft source. The ATG doses used in this group varied from 2.5 mg/kg to 10 mg/kg. Our group has previously explored the outcomes of haplo-HCT with reduced doses of ATG. In view of increased rate of grade III / IV acute GVHD with ATG dose of 2 mg/Kg while combined with PTCy the dose of ATG in our center is 4.5 mg/Kg for recipients of haplo-HCT(27).
Our study reproduces the findings of Moore et al. and demonstrates that the use of PTCTY as a T cell depletion strategy allows for a safe and early stop of immunosuppression post haploHCT. In their study the early cessation group (patients who did not experience grade II-IV aGVHD) stopped the Cyclosporine on day + 142.5 (range 47-1255) versus day + 548 (range 45–816) for the group who experienced aGVHD (28). The incidence of moderate to severe cGVHD was 27.2% for the early cessation group and 41.6% in the early aGVHD group. We can hypothesize that the addition of ATG to the PTCy allows for the earlier discontinuation of Cyclosporine and lower incidence of cGVHD.
The engraftment dates in our cohort are like the ones reported by the other groups and the incidence of graft failure is low. Interestingly, the EBMT ALWP reported a faster neutrophil engraftment in recipients of dual T cell depletion.(26) In our group PBSC was the stem cell source in all of the grafts, with lower rates of graft failure and faster engraftments. The use of PTCy and ATG for GVHD prophylaxis strategy allows for the widespread use of PBSC for recipients of haploidentical allografts and has been reported by Salas et al, El-Cheik et al and Dulery et al (27, 29, 30). Sun et al have reported the outcomes of 13 patients who underwent a second alloHCT for graft failure after haploidentical alloHCT using a different donor, their OS at 1 year was 56.6% (31). Our slightly inferior results could be attributed to the fact that 3 of our 9 patients had to use the same haploidentical donor for their second alloHCT.
The use of dual T cell depletion has been associated with an increase rate of viral reactivations. Our incidence of CMV and EBV reactivation is significantly higher to that reported in the literature, however we did not experience and increased mortality.(32–34) Our group has reported in the past the increased incidence of BSI in recipients of post-transplant cyclophosphamide as part of GVHD prophylaxis (35).
Most recently, with the intention to reduce transplant related toxicity, Dulery et al have reported successful outcomes of reducing the total cyclophosphamide dose from a total 100 mg/kg to 70 mg/kg in patients over the age of 65. The patients received a thiotepa based conditioning regimen. The group reported faster neutrophil and platelet recovery without a significant increase in the risk of GVHD and a higher GRFS than the conventional PTCy regimen(36). Lower incidence of bacteremia and CMV reactivations were reported, EBV reactivation incidence was no different from the standard dose PTCy.
The retrospective nature of our study and the relatively small sample size limit the statistical power of the analysis and induces selection bias.