Stem cell transplant after chimeric antigen receptor therapy in patients with acute lymphoblastic leukemia

This study aimed to investigate if stem cell transplantation (SCT) could improve the long-term prognosis of minimal residual disease negative complete remission (MRD-CR) patients with acute lymphocytic leukemia (ALL) after chimeric antigen receptor-modified (CAR) T-cell therapy. 

This study concluded that this treatment regime was safe and effective for this group of patients.  

Chimeric antigen receptor-modified T-cell (CAR-T) therapy has been shown to be effective and safe for patients with relapsed or unresponsive B-cell acute lymphoblastic leukemia (ALL). CAR-T therapy is a treatment where a patient's T cells (immune cells) are changed in the lab so they will attack cancer cells. CAR-T therapy is limited in terms of long-term leukemia-free survival. New ways to help CAR-T therapy achieve a lasting effect are needed. 

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) involves taking cells from a healthy donor and transplanting them to a patient to make new cells. It was unknown if allo-HSCT could improve long-term outcomes for patients with ALL after they received CAR-T therapy. 

This study involved patients with relapsed or unresponsive ALL. In the first stage, 58 patients received split doses of CART-T cells after lymphodepleting chemotherapy (kills leukemia blood cells before treatment). 87.9% of these patients achieved complete remission (CR – no signs of cancer left). In the second stage, 21 of 47 MRD-CR patients without previous allo-HSCT received allo-HSCT within 3 months after CAR-T therapy. The average follow-up was 7.7 months. 

There was no difference in overall survival (OS) between the MRD-CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS; survival free of complications) and relapse-free survival (RFS; survival without the cancer coming back) were significantly prolonged by allo-HSCT in patients with a high number of cancer cells before the infusion and in those with poor prognostic markers.

This study concluded that CAR-T therapy before allo-HSCT is safe and effective for patients with relapsed or unresponsive ALL. It was also concluded that it may prolong EFS and RFS in cases of high pre-infusion remaining leukemia cells or poor prognostic markers. 

This study had a very small sample size and a short duration of follow-up. Larger studies are needed.