Study Observes Changes in Donor Chimerism in Patients with ALL Receiving CAR T-Cell Therapy

A study published in OncoTargets and Therapy found that CD19 chimeric antigen receptor (CAR) T-cells derived from patients who relapsed after receiving allogeneic hematopoietic cell transplantation (alloHCT) with a low level of donor chimerism were effective for salvage therapy. These T-cells could be restored to complete donor chimerism after 12 days of in vitro culture.

The study included nine patients with B-cell acute lymphocytic leukemia (ALL) who had low donor chimerism levels and relapsed after alloHCT. The first three patients received CD19 CAR T-cell therapy using cells derived from autologous peripheral blood mononuclear cells (PBMCs), comprising a mixture of patient and original donor cells, as their donors could not provide PBMCs.

Samples from the subsequent six patients were investigated in vitro only. The changes in the degree of donor chimerism, function of the CD19 CAR T-cells, and T-cells in all nine patients were analyzed in vitro.

CAR T-cells and T-cells in all nine patients showed complete donor chimerism restoration after a 12-day culture period in vitro. These CD19 CAR T-cells demonstrated strong cytotoxicity toward Nalm 6 cells in vitro except in two patients. In the latter patients, the absolute numbers of all subsets especially the CD8+ T-cell absolute numbers in peripheral blood were very low.

Two patients showed relatively short durations from transplant to recurrence and received chemotherapy after relapse. Among patients receiving CD19 CAR T-cell therapy, the most commonly observed adverse event was grade 1/2 cytokine release syndrome.

No patients had acute graft-versus-host disease during treatment. Among the first three treated patients, the first two achieved complete response with complete restoration of donor chimerism. Patient three, who received the same CD19 CAR-T cell therapy as the first two, did not respond to this therapy.