A Retrospective Review of Response to Donor Leukocyte Infusions In Adults with Acute Myeloid Leukemia After Reduced Intensity Conditioned Allogeneic Hematopoietic Cell Transplantation.
Authors: Nastoupil Loretta , Schroeder Mark A. , Zhang Qin , Geoffrey Uy , Cashen Amanda , Stockerl-Goldstein Keith E. , Abboud Camille N. , Westervelt Peter , DiPersio John F. , Vij Ravi 
Published: October 2019

Abstract
Abstract 4512
Relapse remains the most common cause of death after allogeneic hematopoietic cell transplantation (HCT), and occurs in 40% of all hematologic malignancy patients. Reduced intensity conditioning (RIC) of acute myeloid leukemia (AML) patients for HCT has been adopted as a means to reduce treatment related mortality and graft-versus-host disease (GvHD) after transplantation. The trade off of this approach has been an increased relapse risk. There is limited data on the use of donor leukocyte infusion (DLI) for AML relapse after RIC HCT. We conducted a single center retrospective review of the outcomes of DLI in adults with AML after RIC allogeneic HCT. We hypothesized that DLI given for disease relapse or graft hypoplasia would improve overall survival in patients. A database of patients undergoing hematopoietic cell transplantation (HCT) from 1997 – 2007 were screened and eligible if they had undergone a fludarabine based conditioning regimen. 33 charts were initially selected for review (16 undergoing leukocyte infusion and 17 not undergoing leukocyte infusion). 3 patients in the DLI cohort were excluded because they had undergone a second transplant and 11 patients in the non-DLI cohort were excluded for no evidence of relapse. A cohort of 13 DLI patients and 6 non-DLI controls were included in the analysis. The median age of patients undergoing DLI was 52 (69% males). 8% of recipients had evidence of graft-versus-host disease (GvHD) prior to DLI and 61% were reported to have GvHD after DLI. 46% of transplant recipients had evidence of disease at the time of RIC HCT. 92% of DLI recipients received DLI for disease relapse and all underwent treatment with either chemotherapy or radiation prior to DLI. Those patients receiving DLI had prolonged survival compared to the non-DLI cohort (Wilcoxon chi-square = 4.212, p=0.04). Variables that statistically predicted overall survival in the DLI treated cohort were disease after DLI (Log rank chi-square = 12.636, p=0.002), chronic GvHD after DLI (Log Rank chi-sqare = 3.932, p=0.047), undergoing a HLA matched transplant (Log rank chi-square 5.017, p=0.025) and CMV positive recipient (Log rank chi-square = 4.562, p=0.033). Other variables that were not significant in predicting survival after DLI included: acute or chronic GvHD before DLI, disease specific treatment before DLI, gender, cytokines at the time of transplant or DLI, total number of DLI's, recipient lymphocyte count pre-DLI, immunosuppression at the time of DLI, CD3 dose, leukemic burden measured by blast percentage on bone marrow biopsy pre-DLI, and cytogenetic risk group. We conclude that DLI improves survival for relapsed AML patients after RIC HCT. The risk for GvHD is significant but no patients experienced life threatening GvHD in this cohort. Interestingly, complete HLA matched transplant recipients had improved survival after DLI over mismatched transplant recipients undergoing DLI. Limited by the small sample size, we did not have enough power to conduct multiple regression analysis. In the future we plan to model predictors of overall survival, progression free survival and GvHD after DLI in a larger cohort including myeloablative conditioning in adult patients with AML.

Disclosures:
Schroeder: Genzyme: Research Funding; Celgene: Research Funding; NIH/NHLBI 5K12HL08710703: Research Funding. Westervelt:Novartis: Honoraria; Celgene: Honoraria, Speakers Bureau. DiPersio:Genzyme: Honoraria. Vij:Novartis: Honoraria; Eisai: Speakers Bureau.