Annals of Hematology

, Volume 88, Issue 12, pp 1215–1221

IGHV gene mutational status and LPL/ADAM29 gene expression as clinical outcome predictors in CLL patients in remission following treatment with oral fludarabine plus cyclophosphamide

  • Karim Maloum
  • Catherine Settegrana
  • Elise Chapiro
  • Bruno Cazin
  • Stéphane Leprêtre
  • Alain Delmer
  • Michel Leporrier
  • Brigitte Dreyfus
  • Olivier Tournilhac
  • Beatrice Mahe
  • Florence Nguyen-Khac
  • Claude Lesty
  • Frederic Davi
  • Hélène Merle-Béral
Original Article

DOI: 10.1007/s00277-009-0742-6

Cite this article as:
Maloum, K., Settegrana, C., Chapiro, E. et al. Ann Hematol (2009) 88: 1215. doi:10.1007/s00277-009-0742-6

Abstract

Several prognostic factors can predict the rapid progression in chronic lymphocytic leukaemia (CLL), including IGHV mutational status, cytogenetic abnormalities and, more recently, LPL/ADAM29 expression. In contrast, few studies have been devoted to the influence of these factors on clinical outcome in responding patients after therapy. We here propose to analyse the impact of IGHV gene status, LPL and ADAM29 gene expression on disease-free survival (DFS) and overall survival (OS) in 41 stage B or C CLL patients in remission after oral fludarabine plus cyclophosphamide. The median follow-up was of 64 (16–74) months. Sequencing of IGHV showed mutated (M) VH genes in 16 of 41 cases and unmutated (UM) in 25 cases. Analysis of LPL and ADAM29 expression in 35 of 41 cases showed overexpression of ADAM29 in 17 cases (14 M and three UM) and LPL in 18 cases (all UM). Patients expressing UM IGHV and LPL had shorter DFS and OS when compared to patients expressing M IGHV and/or ADAM29. Furthermore, blood minimal residual disease (MRD) evaluation using four-colour flow cytometry was performed in 33 out the 41 patients. We showed that patients who achieved phenotypic remission displayed longer DFS than those with MRD+. Our results support the use of LPL and ADAM29 gene expression associated to IGHV mutational status for predicting the clinical outcome of patients treated by oral fludarabine + cyclophosphamide and could be considered for treatment strategies.

Keywords

CLLOral fludarabineCyclophosphamideLPLADAM29IGHVMutational status

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Karim Maloum
    • 1
  • Catherine Settegrana
    • 1
  • Elise Chapiro
    • 1
  • Bruno Cazin
    • 2
  • Stéphane Leprêtre
    • 3
  • Alain Delmer
    • 4
  • Michel Leporrier
    • 5
  • Brigitte Dreyfus
    • 6
  • Olivier Tournilhac
    • 7
  • Beatrice Mahe
    • 8
  • Florence Nguyen-Khac
    • 1
  • Claude Lesty
    • 1
  • Frederic Davi
    • 1
  • Hélène Merle-Béral
    • 1
  1. 1.Service d’Hématologie BiologiqueCHU Pitié-SalpêtrièreParisFrance
  2. 2.Service des maladies du sangCHRU de Lille Hôpital HuriezLilleFrance
  3. 3.CLCC H. BecquerelRouenFrance
  4. 4.Service d’Hématologie CliniqueHôpital de ReimsReimsFrance
  5. 5.Service d’Hématologie CliniqueHôpital ClémenceauCaenFrance
  6. 6.Service d’Hématologie CliniqueCHU La MilétriePoitiersFrance
  7. 7.Service d’Hématologie CliniqueHôtel-DieuCHU de Clermont FerrandFrance
  8. 8.Service Hématologie CliniqueCHU Hôtel DieuNantesFrance