Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Research output: Contribution to journalArticle

Abstract

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.

Details

Authors
  • European Research Initiative on CLL (ERIC)
  • Panagiotis Baliakas
  • Theodoros Moysiadis
  • Anastasia Hadzidimitriou
  • Aliki Xochelli
  • Sabine Jeromin
  • Andreas Agathangelidis
  • Mattias Mattsson
  • Lesley Ann Sutton
  • Eva Minga
  • Lydia Scarfò
  • Davide Rossi
  • Zadie Davis
  • Neus Villamor
  • Helen Parker
  • Jana Kotaskova
  • Evangelia Stalika
  • Karla Plevova
  • Larry Mansouri
  • Diego Cortese
  • Alba Navarro
  • Julio Delgado
  • Marta Larrayoz
  • Emma Young
  • Achilles Anagnostopoulos
  • Karin E. Smedby
  • Gunnar Juliusson
  • Oonagh Sheehy
  • Mark Catherwood
  • Jonathan C. Strefford
  • Niki Stavroyianni
  • Chrysoula Belessi
  • Sarka Pospisilova
  • David Oscier
  • Gianluca Gaidano
  • Elias Campo
  • Claudia Haferlach
  • Paolo Ghia
  • Richard Rosenquist
  • Kostas Stamatopoulos
Organisations
External organisations
  • Uppsala University
  • Center for Research and Technology Hellas
  • Munich Leukemia Laboratory (MLL)
  • Vita-Salute San Raffaele University
  • Royal Bournemouth Hospital
  • Hospital Clínic of Barcelona
  • University of Southampton
  • University Hospital Brno
  • George Papanicolaou General Hospital
  • Karolinska Institutet
  • Skåne University Hospital
  • Belfast City Hospital
  • University of Eastern Piedmont
  • University of Barcelona
  • San Raffaele Scientific Institute
  • Oncology Institute of Southern Switzerland
  • Masaryk University
  • Nikea General Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)360-369
Number of pages10
JournalHaematologica
Volume104
Issue number2
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes