Ex Vivo CD34+-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response

Abstract

Ex vivo CD34⁺-selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34⁺-selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34⁺-selected TCD allograft as a calcineurin inhibitor-free intervention for the prevention of GVHD in patients with acute leukemia and MDS.

Keywords: Acute graft-versus-host disease; Chronic graft-versus-host disease; T cell–depleted transplantation.

Figure 1. Cumulative incidence of grade I–IV, II–IV and III–IV aGVHD

The day 180 analysis shows an overall low incidence of aGVHD.

Figure 2. Cumulative incidence of cGVHD at 3-years

The cumulative incidence of cGVHD was low (5%) which includes 9 patients with classical cGVHD and 4 patients with overlap syndrome.

Figure 3. Kaplan-Meier estimate of 1-year CRFS

Landmark analysis for patients engrafted and disease-free at 100 days after allo-HSCT. The 1-year post allo-HSCT CRFS was high at 65%.