Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia.

Mingming Zhang,Huarui Fu,Yanmin Zhao,He Huang,Weiyan Zheng,Yamin Tan,Jimin Shi,Maofang Lin,Yi Luo,Xiaoyu Lai,Jingsong He,Zhen Cai,Linda Bendall

doi:10.1371/journal.pone.0163599

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.

Highlights

The outcome of adult acute lymphoblastic leukemia (ALL) has improved over the past decades with overall survival (OS) reaching 35–50%.[1, 2] high relapse rate has always been the primary element to threaten the long-term survival, and is associated with a dismal survival rate of
We aimed to evaluate the prognostic effect of minimal residual disease (MRD) levels at first achievement of complete remission (MRD at CR1) for adult patients with Philadelphia chromosome-negative (Ph-negative) ALL in chemotherapy and allo-HSCT arms, and further to discover subgroups that benefit from allo-HSCT based on the stratification by MRD at CR1
During the whole treatment cycle, there were different time points for MRD evaluation depending on different protocols, and the cut-off levels of MRD in different time points varied. [4,5,6,7,8,9,10] In this study, we chose the first achievement of CR as the MRD evaluation time point, which could be applied to most patients reaching CR no matter what induction protocols they received

Summary

Introduction

The outcome of adult ALL has improved over the past decades with overall survival (OS) reaching 35–50%.[1, 2] high relapse rate has always been the primary element to threaten the long-term survival, and is associated with a dismal survival rate of

Objectives

Methods

Results

Conclusion