TY - JOUR
T1 - Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
AU - on behalf of The European Research Initiative on CLL (ERIC)
AU - Baliakas, Panagiotis
AU - Moysiadis, Theodoros
AU - Hadzidimitriou, Anastasia
AU - Xochelli, Aliki
AU - Jeromin, Sabine
AU - Agathangelidis, Andreas
AU - Mattsson, Mattias
AU - Sutton, Lesley Ann
AU - Minga, Eva
AU - Scarfò, Lydia
AU - Rossi, Davide
AU - Davis, Zadie
AU - Villamor, Neus
AU - Parker, Helen
AU - Kotaskova, Jana
AU - Stalika, Evangelia
AU - Plevova, Karla
AU - Mansouri, Larry
AU - Cortese, Diego
AU - Navarro, Alba
AU - Delgado, Julio
AU - Larrayoz, Marta
AU - Young, Emma
AU - Anagnostopoulos, Achilles
AU - Smedby, Karin E.
AU - Juliusson, Gunnar
AU - Sheehy, Oonagh
AU - Catherwood, Mark
AU - Strefford, Jonathan C.
AU - Stavroyianni, Niki
AU - Belessi, Chrysoula
AU - Pospisilova, Sarka
AU - Oscier, David
AU - Gaidano, Gianluca
AU - Campo, Elias
AU - Haferlach, Claudia
AU - Ghia, Paolo
AU - Rosenquist, Richard
AU - Stamatopoulos, Kostas
PY - 2019/1/31
Y1 - 2019/1/31
N2 - 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-tofirst- 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-firsttreatment (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.
AB - 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-tofirst- 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-firsttreatment (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.
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U2 - 10.3324/haematol.2018.195032
DO - 10.3324/haematol.2018.195032
M3 - Article
C2 - 30262567
AN - SCOPUS:85061029438
VL - 104
SP - 360
EP - 369
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 2
ER -