Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.

Hematologic relapse after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is associated with a dismal prognosis. Increasing minimal residual disease (MRD) after HSCT had been proved highly effective prognostic factor for post-treatment leukemia relapse. Savage chemotherapy or intensive conditioning followed by a second HSCT may be applied, but associated with a high mortality and a low rate of complete remission. Donor lymphocyte infusion (DLI) has been shown to exert a graft-versus-leukemia (GVL) effect and has been successfully used in patients who relapsed after HSCT.

In this retrospective study, we sought to gain insights of the effect of DLI on clinical outcomes such as graft versus host disease (GVHD), overall survival (OS), disease free survival (DFS), and treatment-related mortality (TRM) in patients with either relapsed hematological malignancies or increasing MRD who underwent HSCT.

DLIs were administered to 25 patients [10(40%) acute myeloid leukemia, 10 (40%) acute lymphoblastic leukemia, 5 (20%) chronic myeloid leukemia]. Patients with Acute leukemia had been treated with myeloablative conditioning (BuCy). Patients with chronic myeloid leukemia had been treated with non-myeloablative conditioning(Flu,ATG and Bu). Infusion of allogeneic hematopoietic stem cells are performed at our institution from 2005 to 2010. GVHD prophylaxis consisted of CsA, MMF and MTX.10 patients were diagnosed of hematologic relapse a median of 259 (30–850) days after HSCT. 15 patients had persistent increasing MRD(monitoring with flow cytometry or RT-PCR for Fusion Gene) after HSCT. DLIs were given to patients who had relapsed hematological malignancies or persistent increasing MRD. Patients with relapsed malignancies were performed reinduction chemotherapy simultaneously. A total of 57 DLIs were administered to 25 patients a median of 809 (92-1981) days after HSCT. The median transplant dose of CD3(+) cells is 4.12*10e7/kg (2.68*10e7/kg–7.97*10e7/kg).

The overall response rate of DLI was 80% for CML, 90% for ALL and 80% for AML.The response rate was 93.3% in patients with increasing MRD, whereas 60% in patients with relapsed malignancies. A total of 10 patients (40%,7 with increasing MRD, 3 with relapsed malignancies) developed acute GVHD. A complete response was achieved in 72% of the patients. TRM was 12% (3 patients with increasing MRD). The Kaplan-Meier estimate of OS and DFS at 3 years after DLI were 62.5% and 60.9%, respectively, with a median follow-up of 411 (32-1509) days for survivors. In patients with increasing MRD, the 3-year OS and DFS after DLI were 78.6% and 77.8%, respectively, with a median follow-up of 531(40-1509) days. In patients with relapsed malignancies,the 3-year OS and DFS after DLI were 40% and 36.8%, respectively, with a median follow-up of 469 (32-1393) days.

Leukemia relapse is a serious therapeutic challenge following HSCT. In this retrospective study, DLIs was proved to be an effectively therapy to prevent relapse and get a better Clinical outcome in leukemia patients. Patients undergone DLI without leukemia relapse had a better outcome than the relapse group. Further strategies are required to detect early relapse in HSCT patients, and DLI may be a strategy to prevent relapse in high risk patients.

No relevant conflicts of interest to declare.