Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia
Adriana Plesa, Charles Dumontet, Eve Mattei, Ines Tagoug, Sandrine Hayette, Pierre Sujobert, Isabelle Tigaud, Marie Pierre Pages, Youcef Chelghoum, Fiorenza Baracco, Helene Labussierre, Sophie Ducastelle, Etienne Paubelle, Franck Emmanuel Nicolini, Mohamed Elhamri, Lydia Campos, Claudiu Plesa, Stéphane Morisset, Gilles Salles, Yves Bertrand, Mauricette Michallet, Xavier Thomas
Adriana Plesa, Charles Dumontet, Eve Mattei, Sandrine Hayette, Pierre Sujobert, Isabelle Tigaud, Marie Pierre Pages, Laboratory of Hematology, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre - Bénite Cedex 69495, France
Adriana Plesa, Charles Dumontet, Ines Tagoug, CRCL, INSERM 1052/CNRS 5286, Lyon FR-69008, France
Youcef Chelghoum, Fiorenza Baracco, Helene Labussierre, Sophie Ducastelle, Etienne Paubelle, Franck Emmanuel Nicolini, Mohamed Elhamri, Claudiu Plesa, Gilles Salles, Mauricette Michallet, Xavier Thomas, Department of Hematology, Hospices Civils de Lyon, Pierre - Bénite Cedex 69495, France
Lydia Campos, Laboratory of Hematology, Nord Hospital, Saint Etienne 42055, France
Stéphane Morisset, Statistical and Clinical Research, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre - Bénite Cedex 69495, France
Yves Bertrand, Department of Pediatric Hematology and BMT, IHOP Lyon, Lyon 69001, France
Author contributions: Plesa A, Dumontet C and Thomas X designed the study, drafted the manuscript and prepared the final version; Chelghoum Y, Baracco F, Labussiere H, Ducastelle S, Paubelle E, Nicolini FE, Plesa C, Salles G, Bertrand Y, Michallet M and Thomas X included patients and collected clinical data; Plesa A, Morisset S and Thomas X performed statistical analysis; Hayette S and Sujobert P performed molecular analyses; Tigaud I and Pages MP performed cytogenetic analyses for all patients; Plesa A collected morphological data; Tagoug I and Elhamri M participated to collecting biological and clinical data; Mattei E participated to collected flowcytometric data; Campos L, Bertrand Y, Michallet M and Salles G revised the final version; all authors approved the final version of the manuscript.
Institutional review board statement: Lyon University Hospital-Hematology Review Board.
Informed consent statement: All clinical trials have been reviewed and approved by a relevant ethic committee and were performed in accordance with the Helsinki declaration of 1975. All patients gave informed consent according to French legislation.
Conflict-of-interest statement: None of the authors have anything to disclose regarding this study.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Adriana Plesa, MD, Laboratory of Hematology, Lyon-Sud Hospital, Hospices Civils de Lyon, 165, Chemin du Grand Revoyet, Pierre - Bénite Cedex 69495, France.
adriana.plesa@chu-lyon.com
Telephone: +33-478862979
Received: January 29, 2017
Peer-review started: February 13, 2017
First decision: May 10, 2017
Revised: October 17, 2017
Accepted: November 8, 2017
Article in press: November 8, 2017
Published online: December 26, 2017
Processing time: 330 Days and 17.9 Hours
AIM
To evaluate the importance of the CD34+CD38- cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival.
METHODS
Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia (AML) were studied between September 2008 and December 2010 at our Institution (Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8C panels and FACS CANTO and Diva software (BD Bioscience).
RESULTS
We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38- population. Using a cut-off value of 1% of CD34+CD38- from total “bulk leukemic cells” we found that a high (> 1%) level of CD34+CD38- blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38- leukemic cells > 1% was an independent predictor of DFS [HR = 2.8 (1.02-7.73), P = 0.04] and OS [HR = 2.65 (1.09-6.43), P = 0.03].
CONCLUSION
Taken together, these results show that a CD34/CD38 “backbone” for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.
Core tip: We analyzed the bone marrow samples of 200 acute myeloid leukemia (AML) patients at diagnosis by multicolour flow cytometry and investigated the prognostic value of the most immature CD34+CD38- population. We showed that a higher then > % level of CD34+CD38- blasts at diagnosis was an independent predictor of disease free survival (DFS) and overall survival in a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells, cytogenetic and molecular risk subgroups. Despite heterogeneity and complexity of AML leukemia stem cells, we could still use CD34+CD38- quantification at diagnosis as useful complementary prognostic parameter for risk-stratification AML patients in future clinical trials.
