Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients
Wolfgang Bethge, Matthias Eyrich, Stephan Mielke, Roland Meisel, Dietger Niederwieser, Paul G. Schlegel, Ansgar Schulz, Johann Greil, Donald Bunjes, Arne Brecht, Jürgen Kuball, Michael Schumm, Vladan Vučinić, Markus Wiesneth, Halvard Bönig, Kasper Westinga, S. Biedermann, Silke Holtkamp, Sandra Karitzky, Michaela Malchow, Christiane Siewert, Rupert Handgretinger, Peter Lang
Abstract
Abstract 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 × 10 6 CD34 + cells/kg and 14.2 × 10 3 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.