RESEARCH ARTICLE
Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia a11111
Mingming Zhang☯, Huarui Fu☯, Xiaoyu Lai, Yamin Tan, Weiyan Zheng, Jimin Shi, Yanmin Zhao, Maofang Lin, Jingsong He, Zhen Cai, Yi Luo*, He Huang* Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China ☯ These authors contributed equally to this work. *
[email protected] (HH);
[email protected] (YL)
OPEN ACCESS Citation: Zhang M, Fu H, Lai X, Tan Y, Zheng W, Shi J, et al. (2016) Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia. PLoS ONE 11(10): e0163599. doi:10.1371/journal.pone.0163599 Editor: Linda Bendall, University of Sydney, AUSTRALIA Received: May 29, 2016 Accepted: September 12, 2016 Published: October 3, 2016 Copyright: © 2016 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and the supporting information files. Funding: This work was funded in part by the Key Project of the National Natural Science Foundation of China (81230014, HH), and the National Natural Science Foundation of China (81370644, YL; 81470307 YZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Abstract We evaluated the prognostic effect of minimal residual disease at first achievement of complete remission (MRD at CR1) in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of 97 patients received treatment in our center between 2007 and 2012 were retrospectively reviewed in this study. Patients were divided into two arms according to the post-remission therapy (chemotherapy alone or allogeneic hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was detected by four-color flow cytometry. We chose 0.02% and 0.2% as the cut-off points of MRD at CR1 for risk stratification using receiver operating characteristic analysis. The 3-year overall survival (OS) and leukemia free survival (LFS) rates for the whole cohort were 46.2% and 40.5%. MRD at CR1 had a significantly negative correlation with survival in both arms. Three-year OS rates in the chemotherapy arm were 70.0%, 25.2%, 0% (P = 0.003) for low, intermediate, and high levels of MRD at CR1, respectively. Three-year OS rates in the transplant arm were 81.8%, 64.3%, 27.3% (P = 0.005) for low, intermediate, and high levels of MRD at CR1, respectively. Multivariate analysis confirmed that higher level of MRD at CR1 was a significant adverse factor for OS and LFS. Compared with chemotherapy alone, allo-HSCT significantly improved LFS rates in patients with intermediate (P = 0.005) and high (P = 0.022) levels of MRD at CR1, but not patients with low level of MRD at CR1 (P = 0.851). These results suggested that MRD at CR1 could strongly predict the outcome of adult ALL. Patients with intermediate and high levels of MRD at CR1 would benefit from allo-HSCT.
PLOS ONE | DOI:10.1371/journal.pone.0163599 October 3, 2016
1 / 11
Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia
Competing Interests: The authors have declared that no competing interests exist.
Introduction The outcome of adult ALL has improved over the past decades with overall survival (OS) reaching 35–50%.[1, 2] However, high relapse rate has always been the primary element to threaten the long-term survival, and is associated with a dismal survival rate of
