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Haematologica. 2018 Sep 27. pii: haematol.2018.195032. doi: 10.3324/haematol.2018.195032. [Epub ahead of print]

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

Author information

1
Uppsala University.
2
Centre for Research and Technology Hellas.
3
MLL Munich Leukemia Laboratory.
4
UniversitĂ  Vita-Salute San Raffaele.
5
Oncology Institute of Southern Switzerland.
6
Royal Bournemouth Hospital.
7
Hospital Clinic de Barcelona.
8
University of Southampton.
9
Masaryk University and University Hospital Brno.
10
G. Papanicolaou Hospital.
11
Karolinska Institutet.
12
Lund University Hospital.
13
Belfast City Hospital.
14
Nikea General Hospital.
15
Amedeo Avogadro University of Eastern Piedmont.
16
Centre for Research and Technology Hellas; kostas.stamatopoulos@gmail.com.

Abstract

Chronic lymphocytic leukemia patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinicobiological differences. Considering this, we assessed prognosis separately within mutated and unmutated chronic lymphocytic leukemia in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet-A mutated chronic lymphocytic leukemia 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 5- and 10-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 unmutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-trearment (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 chronic lymphocytic leukemia 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 chronic lymphocytic leukemia.

KEYWORDS:

Chronic Lymphocytic Leukemia; SHM; prognostic index; prognostication; risk classification

PMID:
30262567
DOI:
10.3324/haematol.2018.195032
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