Donor Lymphocyte Infusions for Relapsed Hematological Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation: Single Center Experience

Introduction:Donor lymphocyte infusion (DLI) is one of the therapeutic options for patients with relapsed or refractory hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). DLI can augment the graft-versus-tumor (GVT) effect; however, it can sometimes induce severe graft-versus-host disease (GVHD) and infectious complications induced by bone marrow aplasia or immunosuppressive therapy. In this study, we wanted to assess the risk factors for GVHD and transplant-related mortality (TRM) as well as disease outcomes according to the reason for DLI in patients who received DLI after allo-HSCT.

Patients and Methods:We retrospectively analyzed 152 patients with various hematological malignancies who received a total of 250 DLI in our center between March 1991 and July 2018 for disease relapse and at different intervals after allo-HSCT. We used our institutional database to evaluate details and characteristics of patients and DLI outcomes. The probabilities of overall survival were calculated from the day of transplantation with Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit.

Results:Median patient age was 34 years (range, 14-67 years); the patient cohort included 96 males (63.2%) and 36.8 female (56%). Patients evaluated in this study were adult patients with acute myeloid leukemia (n=64), chronic myeloid leukemia (n=36), multiple myeloma (n=6), non-hodgkin lymphoma (4), primary myelofibrosis (n=6), myelodisplastic syndrome (n=3), and severe aplastic anemia (n=3). One hundred thirty-six (10.5%) and sixteen (10.5%) patients had sibling (SD) and unrelated donors (UD), respectively. The stem cell source was peripheral blood stem cells (PBSC) in 116 patients (76.3%) and the other 36 patients (23.8%) received bone marrow stem cells (BMSC). Patients underwent an allo-HSCT with a MAC (n= 109) or RIC (n=43) regimens at a median of 12.5 months from diagnosis. Cyclosporine and methotrexate were used as the main graft versus host disease (GVHD) prophylaxis in our cohort. All patients received DLI for relapse or progression. Median number of DLI was 1 (range, 1-5), the median interval between transplant and first DLI was 6 months (range, 3-86 months), median number of infused CD3⁺cells x 10⁶/kg of recipient body weight was 1.5x10⁷(range, 0.5x10⁷- 11.1x10⁷). The median time from relapse to the first DLI was 1.9 months (range, 0.1-32.7 months). Thirty-one patients (21%) developed acute grade II to IV GVHD and 10 patients (7%) developed extensive chronic GVHD. We could not demonstrate the higher CD3+ cell dose of DLI associated with an increased risk of GVHD. Furthermore, none of our patients presented graft hypoplasia after DLI. At a median follow-up from transplantation interval of 16.3 months (range, 0.5-188.2 months), 35 patients were still alive (%60). The OS at 1 and 3 years was 63.4±0.4 and 28.2±0.4, respectively (Figure 1). The primary cause of death was relapse of the original disease in most of the patients, whereas 14 patients died of TRM (15.3%).

Discussion:Various modifications of DLI have been investigated in combination with molecular-targeted agents to enhance the antitumor effect while minimizing GVHD. Therefore, further studies of larger randomized cohorts with high quality data management are required to clarify the role of DLI in relapsed hematological malignancies.

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