Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia.
Several parameters may predict disease severity and overall survival in chronic lymphocytic leukemia (CLL). The purpose of our study of 190 CLL patients was to compare immunoglobulin heavy chain variable region (IgV(H)) mutation status, cytogenetic abnormalities, and leukemia cell CD38 and Zap-70 to older, traditional parameters. We also wanted to construct a simple, inexpensive prognosis score that would significantly predict TTT and survival in patients at the time of diagnosis and help practicing clinicians. In univariate analyses, patients with higher clinical stage, higher leukocyte count at diagnosis, shorter leukocyte doubling time, elevated serum lactate dehydrogenase (LDH), unmutated immunoglobulin heavy chain variable region (IgV(H)) genes, and higher CD38 had a shorter overall survival and time-to-treatment (TTT). CLL cell Zap-70 expression was higher in patients with unmutated IgV(H), and those with higher Zap-70 tended to have shorter survival. IgV(H)4-34 or IgV(H)1-69 was the most common IgV(H) genes used (16 and 12%, respectively). Of those with IgV(H)1-69, 86% had unmutated IgV(H) and had a significantly shorter TTT. A cytogenetic abnormality was noted in 71% of the patients tested. Patients with 11q22 del and 17p13 del or complex abnormalities were significantly more likely to have unmutated IgV(H). We found that a prognostic score constructed using modified Rai stage, cellular CD38, and serum LDH (parameters easily obtained clinically) significantly predicted TTT and survival in patients at the time of diagnosis and performed as well or better than models using the newer markers.
Weinberg
J Brice
JB
Department of Medicine, Division of Hematology, VA and Duke University Medical Centers, 508 Fulton Street, Durham, North Carolina 27705, USA. brice@duke.edu
Volkheimer
Alicia D
AD
Chen
Youwei
Y
Beasley
Bethany E
BE
Jiang
Ning
N
Lanasa
Mark C
MC
Friedman
Daphne
D
Vaccaro
Gina
G
Rehder
Catherine W
CW
Decastro
Carlos M
CM
Rizzieri
David A
DA
Diehl
Louis F
LF
Gockerman
Jon P
JP
Moore
Joseph O
JO
Goodman
Barbara K
BK
Levesque
Marc C
MC
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D014768:Virginia; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1