{Reference Type}: Clinical Trial, Phase I
{Title}: Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.
{Author}: Bethge WA;Eyrich M;Mielke S;Meisel R;Niederwieser D;Schlegel PG;Schulz A;Greil J;Bunjes D;Brecht A;Kuball J;Schumm M;Vucinic V;Wiesneth M;Bonig H;Westinga K;Biedermann S;Holtkamp S;Karitzky S;Malchow M;Siewert C;Handgretinger R;Lang P;
{Journal}: Bone Marrow Transplant
{Volume}: 57
{Issue}: 3
{Year}: 03 2022
{Factor}: 5.174
{DOI}: 10.1038/s41409-021-01551-z
{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 × 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.