B-cell acute lymphoblastic leukemia (B-ALL) is a highly aggressive hematologic malignancy. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for many patients, relapse after transplantation is still a major clinical challenge. Patients who relapse after allo-HSCT typically have very poor outcomes, with a median survival of less than six months and a five-year survival rate of only around 10%. Effective standardized treatment options for this group remain limited.
The emergence of CD19 CAR-T cell therapy has significantly transformed the treatment landscape for relapsed or refractory (R/R) B-ALL. However, questions remain regarding the long-term efficacy and safety of CAR-T therapy in patients who relapse after allo-HSCT, particularly when comparing autologous and donor-derived CAR-T cells.
Recently, a multicenter retrospective study led by Professors Huang He, Hu Yongxian, and Wei Guoqing from the First Affiliated Hospital of Zhejiang University School of Medicine was published in the journal Cytotherapy. The study evaluated the long-term efficacy, safety, and prognostic factors of CD19 CAR-T cell therapy in patients with B-ALL who relapsed after allo-HSCT.
The study included 55 patients with CD19-positive B-ALL who experienced relapse after allo-HSCT between September 2016 and December 2021 across four centers in China. Among them, seven patients received autologous CAR-T cells and 48 received donor-derived CAR-T cells, primarily from their transplant donors. Most patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR-T infusion.
The results showed encouraging outcomes. Among 47 patients evaluated at day 28 after infusion, 67.3% achieved complete remission (CR), and 65.5% achieved minimal residual disease (MRD)-negative CR. These response rates are significantly higher than those typically seen with conventional chemotherapy or donor lymphocyte infusion (DLI). Patients who were in remission before transplantation had a significantly higher likelihood of achieving CR after CAR-T therapy.
With a median follow-up of 32.3 months, the median overall survival was 13.3 months, and the three-year overall survival rate reached 36.2%. Among patients who achieved CR, the median leukemia-free survival was 22.6 months with a three-year leukemia-free survival rate of 37.8%. These results indicate that CD19 CAR-T therapy can provide meaningful long-term survival benefits for this high-risk patient population.
Importantly, the study found no significant difference in overall survival or leukemia-free survival between patients treated with autologous CAR-T cells and those receiving donor-derived CAR-T cells. Autologous CAR-T therapy demonstrated better immune compatibility and lower risks of complications such as cytokine release syndrome (CRS) and graft-versus-host disease (GVHD), while donor-derived CAR-T cells showed stronger activation and expansion but were associated with higher treatment-related mortality.
In terms of safety, cytokine release syndrome was the most common adverse event, occurring in 74.5% of patients, with severe CRS reported in 16.4%. Immune effector cell-associated neurotoxicity syndrome (ICANS) was relatively rare. Acute GVHD occurred in 27.3% of patients after CAR-T therapy, with higher risk observed in patients who had previously undergone haploidentical transplantation or received CAR-T therapy within six months of transplantation.
Overall, this study provides important real-world evidence demonstrating that CD19 CAR-T therapy can achieve high remission rates and meaningful long-term survival in patients with B-ALL who relapse after allo-HSCT. The findings also suggest that both autologous and donor-derived CAR-T therapies are viable options, offering clinicians additional flexibility in selecting personalized treatment strategies for this challenging patient population.
