Low Toxicity and Favorable Overall Survival in Relapsed/Refractory B-ALL following CAR T cells and CD34-selected T Cell Depleted Allogeneic Hematopoietic Cell Transplant.

To define the tolerability and outcome of allogeneic hematopoietic stem cell transplant (allo-HSCT) following CAR T cell therapy, we retrospectively reviewed pediatric/young adult patients with relapsed/refractory B-ALL who underwent this treatment. Fifteen patients (median age 13 years; range 1–20 years) with a median potential follow up of 39 months demonstrated 24-month cumulative incidence of relapse, cumulative incidence of TRM, and OS of 16% (95% CI: 0–37%), 20% (95% CI: 0–40%), and 80% (95% CI: 60–100%), respectively. Severe toxicity following CAR T cells did not impact OS (p=0.27) while greater time from CAR T cells to allo-HSCT (>80 days) was associated with a decrease in OS. In comparing CD34-selected T cell depleted (TCD; n=9) versus unmodified (n=6) allo-HSCT, the cumulative incidence of relapse, TRM, and OS at 24-months was 22% (95% CI: 0–49%) vs 0% (p=0.14), 0% vs. 50% [95% CI: 10–90%] (p = 0.02) and 100% vs. 50% [95% CI: 10–90%] (p=0.02). In this small cohort of patients, CAR T cells followed by a CD34-selected TCD allo-HSCT appears to result in less TRM and favorable OS when compared to unmodified allo-HSCT. There was no evidence that disease control was impacted by the type of consolidative allo-HSCT, which demonstrates the feasibility of this approach.