Whether CAR-T cell bridging to allo-HSCT increases the incidence of graft-versus-host disease in patients with high-risk chronic lymphocytic leukemia

Abstract

Background The TP53 aberration[both del(17p) and TP53 mutations], a high-risk prognostic factor in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), is closely related to drug-resistance, rapid disease progression, and short-term survival. Although novel agents, such as ibrutinib, idelalisib, as well as venetoclax, have shown good responses, allogenic hematopoietic stem cell transplantation (allo-HSCT) has been considered the only approach offered with curative intent.Case presentation We reported a case of young high-risk CLL/SLL patient with Ritcher’s transformation received ibrutinib plus CAR-T cells after the BCL-2 inhibitor venetoclax resistance, and then bridging to allo-HSCT when she had a complete remission (CR). Unfortunately, the patients died on day + 99 after transplantation due to intestinal grade IV acute graft-versus-host-disease (aGVHD) which could not be reversed by intensified immunosuppressive agents, including high-dose glucocorticoid, anti-CD25 monoclonal antibody basiliximab, and small-molecular inhibitors ruxolitinib, ibrutinib, as well as fecal microbiota transplantation (FMT).Conclusion TP53 aberrations in CLL/SLL patients are prone to large cell transformation, and have a poor prognosis, especially in venetoclax-resistant patients. Ibrutinib combined with CAR-T cells offered a treatment option, but whether bridging allo-HSCT following CAR-T cells increased severe aGVHD remained unclear.