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

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.

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.