Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation

Abstract

Purpose: T-cell depletion (TCD) reduces the incidence of graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). However, concerns about relapse, graft rejection, and variability in technique have limited the widespread application of this approach.

Patients and methods: Outcomes of 44 patients receiving HLA-identical sibling TCD grafts using a uniform technique for CD34(+) selection as the sole form of immune suppression were compared with outcomes of 84 patients receiving T-replete grafts and pharmacologic immune suppression therapy (IST).

Results: Groups were similar, except for fewer men (36% with TCD v 56% with IST) and more frequent use of radiation-containing regimens (100% with TCD v 50% with IST) in the CD34-selected TCD cohort. The proportion of patients with neutrophil engraftment at day 28 was similar (96% with IST and 100% with TCD grafts). The 100-day rates of grade 2 to 4 acute GVHD were 39% and 23% with IST and TCD grafts, respectively (P = .07). Corresponding 2-year rates of chronic GVHD were lower with TCD grafts than IST (19% v 50%, respectively; P < .001). There were no differences in rates of graft rejection, leukemia relapse, treatment-related mortality, and disease-free and overall survival rates. At 1 year, 54% and 12% of patients were still on immunosuppression in the IST and TCD cohorts, respectively. TCD was associated with a higher GVHD-free survival at 2 years compared with IST (41% v 19%, respectively; P = .006).

Conclusion: These results suggest that TCD via CD34 selection might lower long-term morbidity as a result of chronic GVHD without negatively impacting relapse rates in patients with acute myeloid leukemia. Additional prospective studies should be undertaken to definitively address the role of TCD in HCT.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Patient selection from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0303 clinical trial of transplantation with T-cell–depleted (TCD) grafts in acute myeloid leukemia (AML) and the BMT CTN 0101 antifungal prophylaxis clinical trial (immune suppression therapy cohort). CR1, first complete remission; CR2, second complete remission; PBSC, peripheral-blood stem cell.

Fig 2.

(A) Cumulative incidence of neutrophil engraftment by treatment arm. (B) Cumulative incidence of platelet engraftment by treatment arm. (C) Cumulative incidence of grade 2 to 4 acute graft-versus-host disease (GVHD) by treatment arm. (D) Cumulative incidence of chronic GVHD by treatment arm. IST, immune suppression therapy; TCD, T-cell depletion.

Fig 3.

(A) Cumulative incidence of leukemia relapse by treatment arm. (B) Cumulative incidence of nonrelapse mortality by treatment arm. (C) Probability of disease-free survival by treatment arm. (D) Probability of overall survival by treatment arm. (E) Probability of graft-versus host disease–free survival by treatment arm. IST, immune suppression therapy; TCD, T-cell depletion.