Αβ-T Cell Depleted Haploidentical Transplantation Following Car-T Therapy Improves Gvhd-Free/Relapse-Free Survival for r/r B-ALL Childrens

AbstractBackground and aim: Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with R/R-ALL, but with high risks of GVHD and relapse.We developed a novel method of graft manipulation based on negative depletion of ab T cells to decrease the relapse and GVHD.

Patients and method: 26 R/R-ALL children, transplanted between November 2020 and June 2022 in Taixin BMT center, were enrolled in the trial. Median age was 6 (1-15) years old and male: female was 13:13. All children were given a fully myeloablative preparative regimen. The condition consisted of Cyclophosphamide (1 × 50 mg/mg, days −10, -3 to −2), fludarabine (1 × 40 mg/m², days −7 to −4), thiotepa(2 × 5 mg/kg, day −4), Bu ( total 90 mg/m², days −7 to −5) and Anti-thymocyte globulin [(ATG-F)] (1 × 15 mg/kg，days −9 to −8 ). TCR αβ-depleted grafts contained a median of 32.3 (11.8-114.3)×106 CD34+ cells/kg, 128.8 (33.1-275.2)×10⁶ NK cells/kg , 2.0 (0.1-3.0)× 10⁵ TCRαβ+T-cells/kg and 33.7 (12.3-142.4)× 10⁶ TCRδγ+T-cells/kg. No patient received any post-transplantation GVHD prophylaxis. 23 patients recieved CarT therapy before transplantation(19 patients recieved CD19carT only, 4 patients recieved CD19carT and CD22carT)

Results: Median time to neutrophil and platelet engraftment was 16.5 (range 12-25) and 9 (range 6-19) days, respectively. Three children experienced primary graft failure except one child, who died from sepsis. The two remaining children could be rescued after re-conditioning and a secondary Haplo-HSCT. Final engraftment was achieved in 25/26 patients. With a median follow-up of 254 days(16d-614d) for surviving patients, None of the patients developed grade III/IV acute graft-versus-host disease (aGVHD) , only three patients (11%) had skin-only, grade I/II aGVHD. No patient developed extensive chronic GVHD. The 2-year probability of chronic GVHD-free, relapse-free survival (GRFS) is 88.1%. Three patients died, the cumulative incidence of non-relapse mortality being 11.9%, whereas no one relapsed, resulting in a 0 % cumulative incidence of relapse.

Summary: These data indicate TCR-ab Depletion haplo-HSCT following CarT threpay is a suitable therapeutic option for children with R/R ALL , with better GVHD-free/relapse-free survival (GRFS).

No relevant conflicts of interest to declare.