Pattern of Use and Outcomes with Donor Lymphocyte Infusion (DLI) and Unmanipulated Stem Cell Boost (SCB) after Allogeneic Hematopoietic Stem Cell Transplant (HSCT): A Single-Center Experience

Abstract

Introduction Relapse and graft failure continue to be 2 major problems after allogeneic HSCT. DLI and/or SCB are capable of inducing complete remission in relapsed disease. However, DLI and SCB are associated with significant risks such as graft versus host disease (GVHD) or aplasia. There is a paucity of information regarding DLI/SCB safety, efficacy and toxicity. A better understanding of the risks and benefits of DLI/SCB after HSCT is an important unmet need. Objectives Our objectives are to provide descriptive characteristics of patients receiving DLI or SCB and information regarding the provided cell therapy (CD3+ and/or CD34+ cell dose). We also aim to evaluate relapses, donor chimerism, graft failure, GVHD, DFS and OS after cellular therapy. Methods Retrospective chart review was completed on all patients who received either DLI or SCB at University of Maryland from 2005-2018. Data were analyzed using SPSS v.25.0, SAS v9.4, and R-software v3.5.1. Continuous variables were summarized as median (range), and categorical variables were presented using frequencies (%). Qualitative and quantitative differences between groups were analyzed by the chi-square and the Fisher's exact test for categorical and the Mann Whitney test for continuous variables. The Kaplan-Meier method was used to estimate the OS and GVHD-free survival with the corresponding 95% confidence interval (CI); the log-rank test was used to compare the survival probabilities for different patients' groups. Results A total of 65 patients underwent either DLI or SCB from 2005-2018. Of these, 38 received DLI, and 27 received SCB. Relapsed disease was the most common indication in 78.9% and 61.5% of DLI and SCB, respectively. The average CD3+/kg dose was 5.6 × 10^6 for DLI and 9 × 10^7 for SCB. Average CD34+/kg dose was 3.8 × 10^6 for SCB patients. One-year OS rate was 54.2% for DLI and 37.5% for SCB. Two-year OS rate of OS was 50.3% for DLI and 26.8% for SCB. Remission rates from relapsed disease were 43.4% for DLI and 31.3% for SCB. One-year GVHD-free survival following cell therapy was 51.2% for DLI and 34.4% for SCB. This dropped to 35.3% for DLI and 24.6% for SCB at two years. The differences seen in OS and GVHD between the 2 cohorts were not statistically significant. Conclusion Our overall survival data is favorable compared to recently published data. However, this comes at the expense of GVHD with long-term rates of GVHD-free survival measuring 25-35%. The use of unmanipulated cryopreserved SCB for relapse disease is underreported in the literature. We observed comparable long-term survival and GVHD in both cohorts. Cellular therapy with DLI or SCB remains a viable treatment modality with reasonable long-term outcomes for relapsed/refractory hematologic malignancies after allogeneic HSCT.