The Impact of Allogeneic Hematopoietic Stem-Cell Transplantation on Outcome of the Patients with Intermediate-Risk Acute Myeloid Leukemia
Authors: Wang Ying , Wei Hui , Lin Dong , Zhou Chunlin , Liu Bingcheng , Qiu Shaowei , Gong Benfa , Zhang Guangji , Liu Kaiqi , Wei Shuning , Liu Yuntao , Gong Xiaoyuan , Zhao Xingli , Li Yan , Gu Runxia , Mi Yingchang , Wang Jianxiang 
Published: October 2019

Abstract
Background:
Patients with AML who obtain first complete remission (CR) are subsequently treated with post-remission treatment, including chemotherapy or hematopoietic stem cell transplantation (HSCT). Suitable post-remission treatment in patients with intermediate-risk acute myeloid leukemia (AML) is remaining investigation.
Objectives:
To retrospectively investigatethe value of allo-HSCT in the patients with intermediate-risk AML.
Patients and Methods:
From August 2010 to January 2016, newly diagnosed adultpatients (15 to 55 years old) with AML were consecutivelyenrolled in a prospective trial (ChiCTR-TRC-10001202). Patients were assigned HAD containing conventional dose of cytarabine (homoharringtonine, cytarabine (Ara-c), and daunorubicin) induction therapy (Ara-C 100mg/m2, d1-7) or HAD containing intermediate dose Ara-c (Ara-C 100mg/m2, d1-4, 1.0g/m2, q12h, d5-7). All patients who achieved CR received either high dose Ara-c or intermediate dose Ara-c plus anthracyclines. Allo-HSCT was based on therapeutic responseand patients' intention. Patients received 6 courses of consolidation therapy if they did not receive HSCT. Minimal residual disease (MRD) was analyzed by multi-color flow cytometry after induction and consolidation therapy.
Results:
181 enrolled patients were intermediate-risk AML (median age 36 years old). The median follow-up was 15.5 (0.5-67.9) months. One patient was lost to follow-up after induction, 180 patients were evaluated. 128 patients (71.1%) achieved CR after one induction cycle, 7 patients (3.9%) were early death, and 45 patients (25.0%) did not achieve CR. Forty patients received allo-HSCT, 33 of them were in CR1. The median time from diagnosis to transplantation was 6.5(3.9-16.0) months. Three years overall survival (OS) of transplantation group was higher than that of chemotherapy group (78.0% vs 48.0%, P = 0.000). Three years relapse-free survival (RFS) was 42.0% and 45.0% for patients in transplantation group and chemotherapy group, respectively (P = 0.196).
However, taking transplantation time into account, the outcome was different. If the median transplantation time (6.5 months) was defined as cut-off value, there is no statistically difference of 3 years OS (77.0% vs 69.0%, P=0.182) and 3 years RFS (42.0% vs 53.0%, P=0.320) between transplantation and chemotherapy groups in the patients without relapse within 6.5 months. Twenty-one patients relapsed within 6.5 months, only one of them proceeded to allo-HSCT, and 1 year OS was 29.0%. For 45 patients who did not achieve CR after one induction cycle, 3 years OS was much better by allo-HSCT as compared with chemotherapy (85.0% vs22.0%, P = 0.008).
In order to evaluate prognosis earlier, we analyzed MRD by flow cytometry after induction, first and second consolidation cycles in those achieving CR after one induction cycle. The patients with once or more MRD positive of three time points had significantly inferior 6 months RFS than those with continuous MRD negative (61.0% vs 92.0%,P = 0.005). Similar trend was observed on 1 year RFS (46.0% vs 76.0%, P = 0.005).
Conclusion:
According to the actual treatment, the OS of the patients with intermediate-risk AML was improved by allo-HSCT. When transplantation time was considered in the analysis, there was no difference between allo-HSCT and chemotherapy in survival. The patients with poor early response to chemotherapy (those did not achieve CR after one induction cycle) really benefited from allo-HSCT. The patients without continuous MRD negative after induction, first and second consolidation cycles trended to be early relapse, they might be another subgroup benefiting from allo-HSCT.
Acknowledgments: This study was supported, in part, by State Key Program of National Natural Science of China (81430004), Foundation for Innovative Research Groups of the NaturalScience Foundation of China (81421002).

Disclosures
No relevant conflicts of interest to declare.