Outcomes of Hematopoietic Cell Transplantation in Patients with Refractory Acute Myeloid Leukemia
Authors: Im Annie , Gill Navkiranjit , Cunningham Diana , Agha Mounzer , Raptis Anastasios , Hou Jing-Zhou , Redner Robert L. , Phillips Julie , Boyiadzis Michael 
Published: October 2019

Abstract
Abstract 4531

Background:
Hematopoietic cell transplantation (HCT) can be curative for patients with acute myeloid leukemia (AML) refractory to initial chemotherapy or refractory to re-induction after relapse. However, HCT for AML not in complete remission (CR) can be associated with high treatment related mortality and disease relapse or progression. Pre-transplantation variables that have previously been shown to influence survival in these patients include performance status, duration of first CR, cytogenetic risk group, donor type and presence of circulating blasts. In the current study, our aim was to evaluate outcomes of HCT in patients with refractory AML, and to determine factors that may be predictive of survival.

Methods:
Patients with refractory AML were identified from a database of patients who received allogeneic HCT at the University of Pittsburgh Cancer Institute from 2000–2012. Subjects were included if they had relapsed AML that did not respond to re-induction chemotherapy (n=35), or had persistent leukemia after initial induction chemotherapy at diagnosis (primary induction failure) (n=36). Rates of CR and CR with incomplete blood count recovery (CRi) were calculated at day 30 and day 100 after HCT, and 3-year and 5-year overall survival (OS) rates were determined using the Kaplan Meier method. Cox proportional hazards regression was used to examine associations between factors of interest and overall survival. The factors of interest included gender, age, relapsed AML versus primary induction failure, primary or secondary AML, cytogenetic risk group, duration of initial CR (for patients in relapse), performance status, number of previous induction chemotherapy cycles, presence of circulating blasts, percentage of blasts in bone marrow prior to transplant, matched unrelated versus sibling donor, donor-recipient sex match, donor-recipient CMV status, and incidence of acute GVHD. Patients were then assigned risk scores based on 5 pre-transplantation predictive factors previously described (J Clin Oncol 2010;28:3730–3738), and overall survival between the risk groups based on these scores were compared.

Results:
The study cohort consisted of 71 patients (median age 44 years, range 19–64 years) who underwent allogeneic HCT for refractory AML. Fifty-eight of 71 (82%) patients received myeloablative conditioning regimens using busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, and the remaining (18%) received reduced-intensity fludarabine-containing regimens. The majority of patients received cyclosporine with methotrexate for GVHD prophylaxis. At day 30 after HCT, CR rate was 31%, and CRi rate was 49%, for a total 80% response rate. At day 100 after HCT, 51% remained in CR or CRi. Three-year OS rate was 12.3% (CI 5.6–21.8), 5-year OS rate was 10.5% (CI 4.4–19.7), and median OS was 0.57 years (CI 0.35–0.75). Among the factors evaluated, donor type was found to be significantly associated with OS in univariate and multivariate analyses, with higher risk of death from matched unrelated versus sibling donor (HR 1.74, 1.02–2.96). Younger age at HCT was also associated with improved survival (p<0.06). Of the 60 patients who were deceased at time of analysis, 38.6% died from progressive leukemia, 38.6% from infection, 5.3% from GVHD, and 7% from other causes. The incidence of acute GVHD overall was 50.7%, and occurred in 10 of the 22 patients who died from infection. Based on the risk scores using the 5 previously described predictive factors, there were 6 patients with risk score 1, 13 patients with risk score 2, and 38 patients with risk score≥3. 3-year OS was not significantly different in patients with risk score 1 or 2 compared with score≥3 (16.7% and 15.4% versus 10.2%, respectively), though the numbers in each group were small.

Conclusion:
Despite high CR and CRi rates after HCT for patients with refractory AML, 3-year and 5-year OS rates were 12.3% and 10.5%, respectively. Only donor type was significantly associated with OS, though there was a trend for patient age. Though patients with AML in relapse or primary induction failure represent a high-risk group to undergo HCT, the initial high response rates through day 100 suggest the potential role of maintenance therapy after HCT or strategies for modulating immunosuppressive therapy in order to improve survival in this population.

Disclosures:
No relevant conflicts of interest to declare.