title: Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation.
abstract: This study evaluated the prognostic value of minimal residual disease (MRD) monitoring by four-color flow cytometry (FCM) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). MRD was examined with four-color FCM at different time points in 139 patients (including pediatric and adult patients) with ALL after allo-HSCT. Real-time quantitative polymerase chain reaction (RQ-PCR) was applied to evaluate the MRD of Philadelphia chromosome-positive ALL (Ph+ ALL) patients. Patients who were FCM-positive (FCM+) after transplantation had a lower event-free survival (EFS) of 0.54 and a higher cumulative incidence of relapse (CIR) of 0.54 compared to an EFS of 0.80 and a CIR of 0.08 in FCM-negative (FCM-) patients (EFS, p < 0.001; CIR, p < 0.001). Similar results were obtained in high-risk patients and Ph+ ALL patients. Moreover, a FCM+ status after the second month post-HSCT (defined as MRD positive) proved to be a predictor of leukemia relapse. Multivariate analysis for EFS, OS and CIR showed that MRD status after transplantation was an independent prognostic factor (p < 0.001, p = 0.013, and p < 0.001, respectively). A good correlation was found between the MRD results of FCM and RQ-PCR (n = 126 pairs, Spearman r = 0.8139, p < 0.001). MRD monitoring by four-color FCM post-transplantation is an important tool for relapse prediction in ALL patients. Prompt and appropriate pre-emptive anti-leukemia treatment could be considered based on the status of MRD after HSCT.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, No 11 Xizhimen South Street, Beijing, 100044, People's Republic of China.
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Zhao
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.forename: Hong-Hu
authors.initials: HH
authors.lastname: Zhu
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Liu
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control* / Q000601:surgery*; D011379:Prognosis; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous