Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.
Wolfgang Andreas BethgeMatthias EyrichStephan MielkeRichard P MeiselDietger NiederwieserPaul G SchlegelAnsgar S SchulzJohann GreilDonald BunjesArne BrechtJürgen H E KuballMichael SchummVladan VucinicMarkus WiesnethHalvard BonigKasper WestingaStefanie BiedermannSilke HoltkampSandra KaritzkyMichaela MalchowChristiane SiewertRupert HandgretingerPeter LangPublished in: Bone marrow transplantation (2021)
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.
Keyphrases
- end stage renal disease
- peripheral blood
- ejection fraction
- chronic kidney disease
- newly diagnosed
- prognostic factors
- bone marrow
- randomized controlled trial
- stem cell transplantation
- peritoneal dialysis
- clinical trial
- stem cells
- type diabetes
- patient reported outcomes
- acute myeloid leukemia
- study protocol
- signaling pathway
- low dose
- immune response
- young adults
- patient reported
- high dose
- multiple myeloma
- oxidative stress
- dendritic cells
- high intensity
- free survival
- coronary artery disease
- childhood cancer