HSCT and CAR-T: a power couple-but who serves whom?

Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy are two major therapeutic approaches for hematologic malignancies. HSCT can provide durable disease control through conditioning-induced tumor cytoreduction, immune reconstitution, and graft-versus-leukemia effects, whereas CAR-T therapy provides antigen-specific antitumor activity and has reshaped the treatment landscape for relapsed or refractory leukemia, lymphoma, and multiple myeloma (MM). Despite these advances, both therapeutic approaches continue to face multiple challenges. HSCT is limited by disease relapse and transplant-related complications, while CAR-T therapy is challenged by antigen escape, limited persistence, and treatment-related toxicities. Increasing clinical experience suggests that HSCT and CAR-T therapy should not be viewed as competing strategies, but rather as complementary therapeutic approaches whose value depends on disease characteristics, depth of response, immune recovery, and transplant feasibility. On the one hand, CAR-T therapy can reduce tumor burden before transplantation, be incorporated into modified conditioning regimens, or be used after allogeneic HSCT (allo-HSCT) as prophylactic, preemptive, or salvage cellular therapy. On the other hand, HSCT can consolidate CAR-T-induced remission, provide hematopoietic support in selected settings, and create a post-transplant immune environment that may facilitate subsequent CAR-T-cell therapy. In this review, we summarize the current evidence for HSCT-CAR-T integration in leukemia, lymphoma, and MM. We discuss major integration strategies, including HSCT after CAR-T therapy, CAR-T-assisted conditioning, autologous stem cell transplantation (ASCT)-CAR-T sequential strategies, and CAR-T therapy after allo-HSCT. We aim to help match appropriate patients to the most suitable HSCT-CAR-T strategies and thereby improve clinical decision-making.