Influence Of Donor Source On Relapse and Survival In Patients With Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Analysis From The Japan Society For Hematopoietic Cell Transplantation (JSHCT) AML Working Group
Authors: Yano Shingo , Yokoyama Hiroki , Uchida Naoyuki , Kakihana Kazuhiko , Fukuda Takahiro , Kanamori Heiwa , Ogawa Hiroyasu , Nagamura Tokiko , Tanaka Junji , Morishima Yasuo , Atsuta Yoshiko , Takami Akiyoshi 
Published: October 2019

Abstract

Background
Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for the patients with acute myeloid leukemia (AML), but a major obstacle to success is represented by the relapse of the disease. Donor T lymphocytes can induce graft-versus-leukemia (GVL) effect, and it contributes to eliminate leukemic cells. We retrospectively analyzed the risk of relapse after allo-HCT for the patients with AML. Purpose of this study is to determine the impact of donor sources for the risk of relapse and survival.

Patients and Methods
Clinical data were collected from the Transplant Registry Unified Management Program (TRUMP) in Japan. An individual patient data-based analysis was performed on patients with AML who underwent allo-HCT between 2006 and 2010. Patients with CR1 or CR2 were defined as having standard-risk disease, and patients with CR3≤ or non-CR were defined as having advanced-risk disease. Cox proportional hazards models were used to evaluate variables that may affect overall survival. Fine and Gray proportional-hazards model were used to evaluate variables that may affect morphologic relapse. Death in remission was treated as a competing risk when analyzing cumulative incidence of relapse. Death or relapse without GVHD was treated as a competing risk for acute and chronic GVHD.

Results
We analyzed a cohort of 3,829 patients with AML: 543 (14%) received bone marrow from related donors (RBM), 768 (20%) received peripheral blood from related donors (RPB), 1,576 (41%) received bone marrow from unrelated donors (URBM), and 942 (25%) received cord blood (CB). The median age at allo-HCT was 46 years (range, 16 to 65 years). The cumulative incidence of relapse at 5 years in all-risk patients, standard-risk disease, and advanced-risk disease were 36%, 22%, and 42%, respectively. The 5-year unadjusted OS rates in all-risk patients, standard-risk patients and advanced-risk patients were 44%, 61%, and 26%, respectively. In multivariate analysis, the uses of antigen matched URBM (HR 0.47, 95% CI 0.36-0.61, p<0.01), antigen mismatched URBM (HR 0.63, 95%CI 0.42-0.96, p=0.03) or CB (HR 0.63, 95% CI 0.42-0.94, p=0.02) were associated with a decreased risk of relapse as compared with matched RBM in standard-risk group. But these grafts were associated with an increased risk of non-relapse mortality (NRM) (matched URBM: HR 2.0, p<0.01, mismatched URBM: HR 3.17, p<0.01, CB: HR 2.42, p<0.01); these grafts were not associated with favorable OS (matched URBM: HR 0.9, p=0.60, mismatched URBM: HR 1.47, p=0.02, CB: HR 1.22, p=0.22) than using matched RBM. The use of matched RPB (HR 0.85, 95%CI 0.63-1.14, p=0.28) did not decrease a risk of relapse. In engrafted patients with standard-risk disease, the uses of antigen matched URBM (HR 1.29, 95% CI 1.02-1.62, p=0.03), antigen mismatched URBM (HR 2.27, 95%CI 1.68-3.06, p<0.01), and CB (HR 1.58, 95% CI 1.22-2.05, p<0.01) were associated with an increased incidence of grade II-IV acute GVHD as compared with matched RBM. There was no difference in development of chronic GVHD among these donor sources.

Conclusion
In this study, we found that the uses of URBM and CB for standard-risk patients could reduce risk of relapse, but they did not result in a favorable OS. Reduction of NRM could in part be attributed a better outcome in standard-risk patients who transplanted from URBM or CB. However, it is difficult to determine how much of the benefit is attributed to the incidence of GVHD after allo-HCT, the use of URBM and CB were associated with a higher incidence of grade II-IV acute GVHD compared with matched RBM. Although relapse is the major cause of treatment failure after allo-HCT, immune modulation mediated by donor T lymphocytes may play a role in disease control for the patient with AML.

Disclosures:
No relevant conflicts of interest to declare.