Outcomes of Allogeneic Transplantation in Patients Aged ≤ 60 Years with Acute Myeloid Leukemia in Second Complete Remission: A CIBMTR ® Cohort Analysis

Introduction: Allogeneic hematopoietic cell transplantation (HCT) has demonstrated survival benefit in younger patients with intermediate/high-risk acute myeloid leukemia (AML), while data for older patients transplanted in CR2 in particular are limited.  The purpose of the presented study was to retrospectively investigate within the CIBMTR database parameters that influence post-transplant outcome for patients aged ≥60 undergoing allogeneic HCT for AML in CR2.

Methods: Using the CIBMTR database, patients aged ≥60 years with AML in CR2 who underwent HCT between 2001 and 2012 were identified. A number of patient, disease and transplant-related variables were analysed, and outcomes studied included overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM).

Results: In total, 196 patients with AML in CR2 met the eligibility criteria for this study. Median follow-up of survivors was 73 (6-123) months. Median age at transplant was 64 years (range 60-78), 81 patients (41%) were female. Seventy one percent had a Karnofsky performance status ≥90%. De novo AML was diagnosed in 147 patients (75%). Concerning cytogenetics at diagnosis (SWOG/ECOG), 16 patients (8%) were favorable, 133 (68%) were intermediate and 17 (9%) were unfavorable risk, while 30 patients (15%) had missing data. Concerning duration of CR1, 48 patients (24%) demonstrated <6 months, 48 patients (24%) 6-12 months and 74 patients (38%) ≥12 months, missing data in 26(13%). Myeloablative conditioning regimens were used in 37 patients (19%). Fifty-eight patients (30%) had matched sibling donors, 99 (51%) were well-matched unrelated and 39 (20%) were partially matched unrelated. Peripheral blood stem cells were used in 171 patients (87%), 58 patients (30%) received in vivo T-cell depletion.

Univariate analysis demonstrated a 3-year OS of 42% (95% confidence intervals [CI] 35-49), LFS of 37% (95% CI 30-44), NRM of 25% (95% CI 19-32), and CIR of 38% (95% CI 31-45). Cumulative incidence of acute GvHD at 100 days was 33% (95% CI 26-40) while chronic GvHD at 3-years was 54% (95% CI 46-61).

Cytogenetics was the only independent risk factor (relative risk [RR] 1.14 (95% CI 0.59-2.19) and 2.32 (95% CI 1.05-5.14) for intermediate and unfavorable risk respectively) for survival in multivariate analysis. For CIR, cytogenetic risk was the predominant prognostic factor (RR 1.10 (95% CI 0.47-2.56) and 2.98 (95% CI 1.11-8.00) for intermediate and unfavorable risk respectively, p=0.008). A higher NRM was observed with bone marrow graft source (RR 2.75, p=0.002) and male gender (RR 2.04, p=0.02). 

Conclusion: This study demonstrates the potential of long-term remissions with HCT in selected older patients with AML in CR2. Patients with adverse risk cytogenetics had very poor outcome due to higher risk of post-transplant relapse, and novel strategies are required for these patients.