Case Report: Anti-CD7 CAR-T cell therapy in two patients with relapsed/refractory acute leukemia of ambiguous lineage with aberrant CD7 expression

Background Acute leukemia of ambiguous lineage (ALAL) presents a formidable therapeutic challenge, marked by high relapse rates and dismal long-term survival. The optimal treatment strategy, particularly for acute undifferentiated leukemia (AUL), remains elusive. CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown considerable promise in treating T-cell malignancies. Consequently, for patients with relapsed or refractory ALAL who exhibit abnormal CD7 expression, CD7-CAR-T cell therapy represents a promising but still preliminary therapeutic avenue that warrants further investigation. This study aims to evaluate the efficacy and safety of CD7 CAR-T cell therapy in this specific patient population. Methods Two patients with relapsed/refractory (R/R) ALAL and aberrant CD7 expression participated in a clinical trial of CD7 CAR-T therapy (YK-CD7BB-BL4–002 vector). Patient 1, diagnosed with mixed phenotype acute leukemia (MPAL, B/My), received autologous CD7 CAR-T cells (9.0×10^5cells/kg) after lymphodepleting chemotherapy. Patient 2, diagnosed with acute undifferentiated leukemia (AUL), was treated with donor-derived CD7 CAR-T cells (10.4×10^5cells/kg). Safety and efficacy were evaluated through bone marrow assessment, flow cytometry, and molecular monitoring. Results Both patients attained swift CD7-negative morphological complete remission (CR) with flow-MRD negativity, but low-level detectable PICA LM- MLLT10 fusion transcript (0.14%) by RT-qPCR persisted on day 15 in Patient 2 (above the RT-qPCR LoD of 0.01%); Patient 1 achieved molecular remission ( RPN1-MECOM undetectable) on day 19. Patient 1 proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT)within two weeks of remission but suffered a molecular relapse at 3 months post-transplant, ultimately leading to death. Patient 2 achieved flow-MRD-negative marrow remission with residual low- level PICALM-MLLT10 transcript; however, peripheral blood PICALM-MLLT10 fusion gene levels surged dramatically by day 42, indicating extramedullary/systemic molecular relapse despite persistent BM flow-MRD negativity. Both patients developed profound myelosuppression and prolonged cytokine release syndrome (CRS). Patient 2 experienced grade 3 CRS and fatal neurotoxicity most consistent with probable ICANS accompanied by progressive cranial nerve deficits. Conclusions CD7-directed CAR-T therapy can induce rapid morphological and flow-MRD-negative remission in these two patients with heavily pretreated R/R ALAL and aberrant CD7 expression. Nevertheless, early relapse patterns and significant toxicities—notably severe neurotoxicity in the transplantation context —highlight the imperative for meticulous patient selection, robust supportive care, and combinatorial strategies to consolidate remission. Large-scale prospective trials are urgently warranted to define the definitive role of this therapy in ALAL. Clinical trial registration: