%0 Clinical Trial, Phase I
%T Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.
%A Bethge WA
%A Eyrich M
%A Mielke S
%A Meisel R
%A Niederwieser D
%A Schlegel PG
%A Schulz A
%A Greil J
%A Bunjes D
%A Brecht A
%A Kuball J
%A Schumm M
%A Vucinic V
%A Wiesneth M
%A Bonig H
%A Westinga K
%A Biedermann S
%A Holtkamp S
%A Karitzky S
%A Malchow M
%A Siewert C
%A Handgretinger R
%A Lang P
%J Bone Marrow Transplant
%V 57
%N 3
%D 03 2022
%M 34952929
%F 5.174
%R 10.1038/s41409-021-01551-z
%X Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.