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Dual T cell depletion for GvHD prophylaxis in adults post-haplo-HCT

Mar 29, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in graft-versus-host-disease.

The use of peripheral blood stem cells in haploidentical hematopoietic cell transplantation (haplo-HCT) has been associated with increased incidence of acute and chronic graft-versus-host disease (GvHD), 1 Posttransplant cyclophosphamide (PTCy) combined with antithymocyte globulin (ATG), and cyclosporine (CsA) has been used to prevent GvHD in a haplo-HCT setting.1

Moya et al.1 published a study in Bone Marrow Transplantation sharing real-world experience of ATG-PTCy-CsA in peripheral blood haplo-HCT. Here, we summarize the key findings.

Study design1

  • A retrospective study of clinical data from adult patients who received peripheral blood haplo-HCT between October 2015 and December 2021 at Princess Margaret Cancer Centre, Toronto, Canada.
  • Patients received dual T-cell depletion with ATG and PTCy at a dose of 50 mg/kg/day for 2 days followed by CsA 2.5 mg/kg intravenously every 12 hours from Day +5
    • Patients received either 4.5 mg/kg or 2 mg/kg of ATG
    • CsA was titrated to a therapeutic level ranging between 200 and 300 ng/ml and maintained therapeutic until Day +60 in the absence of GvHD
  • To determine the outcomes of ATG-PTCy-CsA for haplo-HCT performed from peripheral blood stem cell grafts, the following were measured:
    • cumulative incidence of Grade 2–4 and Grade 3–4 acute GvHD at Day 100;
    • cumulative incidence of moderate to severe chronic GvHD at 1 and 2 years; and
    • overall survival and non-relapse mortality at 1 and 2 years.

Key findings1

  • In total, 157 patients were included in this study, with a median age of 57 years.
  • Overall survival was 57.4% (95% confidence interval [CI], 48.8─65.1%) at 1-year posttransplant and 49.4% (95% CI, 40.4─57.7%) at 2-years posttransplant.
  • Non-relapse mortality was 31.6% (95% CI, 24.2─39.2%) and 36.6% (95% CI, 28.5─44.7%) at 1 and 2 years, respectively. Figure 1 summarizes other posttransplant outcomes.

Figure 1. Outcome variables in patients who received ATG-PTCy-CsA prophylaxis* 

aGVHD acute graft-versus-host disease; ATG, antithymocyte globulin; cGvHD, chronic GvHD; CsA, cyclosporine; PTCy, posttransplant cyclophosphamide.
*Data from Moya, et al.1


  • The administration of 2 mg/kg of ATG (p = 0.003) and the selection of donors older than 40 years (p = 0.011) increased the risk of Grade 3–4 acute GvHD.
  • Overall, 46.5% of patients died with the leading causes of death being infections and relapse.

Key learnings

  • A dose of 4.5 mg/kg of ATG paired with a selection of younger donors is an effective prophylaxis of GvHD with acceptable relapse rates.
  • Dual T-cell depletion using the PTCy-ATG-CsA combination is safe in patients undergoing peripheral blood haplo-HCT.

  1. Moya TA, Salas MQ, Carreira AS, et al. Dual T cell depletion for graft versus host disease prevention in peripheral blood haploidentical hematopoietic cell transplantation for adults with hematological malignancies. Bone Marrow Transplant. 2024. Online ahead of print. DOI: 1038/s41409-024-02216-3


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