A successful haploidentical transplantation without conditioning regimen for a relapsed/refractory multiple myeloma patient after chimeric antigen receptor T-cell therapy

Background aims: With novel therapies improving prognosis, the complications of multiple myeloma after multi-line treatment, particularly myelosuppression, have become a crucial determinant of long-term outcomes. Non-myeloablative allogeneic hematopoietic stem cell transplantation is a feasible option, but the transplant-related mortality rate remains high. Our study presents a relapsed/refractory multiple myeloma patient with a 9-year disease history. Methods: The patient underwent multiple chemotherapy treatments and achieved partial remission. The patient then received two B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell treatments with lymphodepletion conditioning of fludarabine and cyclophosphamide. Results: At the fifth month after the second CAR T-cell treatment, the patient achieved complete remission but developed refractory myelosuppression (grade 4 according to Common Terminology Criteria for Adverse Events 5.0) after several severe infections. In order to facilitate hematopoietic recovery, her daughter's stem cells were infused into her, which fortunately implanted without conditioning. After thrombotic microangiopathy and acute graft-versus-host disease, the patient was discharged with consistent full donor chimerism. We assume this engraftment may be attributed to the patient's severe hematopoietic failure and further host lymphodepletion by fludarabine. Conclusions: This study highlights the potential of allogeneic hematopoietic stem cell transplantation with reduced conditioning intensity or even the omission of conditioning, particularly for a relapsed/refractory multiple myeloma patient who struggles with severe myelosuppression after long-term treatment. (c) 2025 Published by Elsevier Inc. on behalf of International Society for Cell & Gene Therapy.