Background and Objective

Patients with high‑risk hematologic cancers remain at elevated risk of relapse even after hematopoietic stem cell transplantation (HSCT). The investigators aim to determine whether early administration of donor lymphocyte infusion (DLI) on day 7 post‑transplant can reduce relapse incidence.

Population and Design

Eligible participants are adults aged 18–65 with high‑risk acute leukemias, lymphomas, myelodysplastic syndromes, or multiple myeloma who have demonstrated poor response to standard therapy or possess a high likelihood of relapse. The study is a combined Phase 1/2 trial that commenced in May 2022 and is actively enrolling. Subjects will be hospitalized at the NIH Clinical Center for approximately four weeks, followed by a minimum of 100 days of post‑transplant monitoring and a five‑year follow‑up period.

Mechanism of Action

Donor lymphocyte infusion introduces donor immune cells that recognize and attack recipient malignant cells, thereby promoting post‑transplant immune reconstitution and facilitating tumor eradication. However, there is an associated risk of immune‑mediated adverse events, notably graft‑versus‑host disease (GVHD).

Expected Benefits and Risks

Early DLI has the potential to markedly reduce post‑transplant relapse rates, thereby improving overall survival. Conversely, an increased incidence of GVHD could complicate management and raise treatment costs. Consequently, a rigorous assessment of the safety profile is a primary objective.

Future Outlook

If successful, this study could shift the therapeutic paradigm for high‑risk hematologic malignancies by incorporating early immune augmentation into standard care. A negative outcome would underscore the need to refine DLI timing or dosing strategies.