Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors.
This study evaluates the prognostic significance of genetic abnormalities (detected at or shortly after presentation), clinical stage, lymphocyte morphology, CD38 expression, and IGVH gene status in 205 patients with chronic lymphocytic leukemia (B-CLL). Deletion of chromosome 11q23, absence of a deletion of chromosome 13q14, atypical lymphocyte morphology, and more than 30% CD38 expression are significantly associated with the presence of unmutated IGVH genes. Advanced stage, male sex, atypical morphology, more than 30% CD38 expression, trisomy 12, deletion of chromosome 11q23, loss or mutation of the p53 gene, and unmutated IGVH genes are all poor prognostic factors in a univariate analysis. However, only 98% or more homology of IGVH genes to the germline sequence, loss or mutation of the p53 gene, and clinical stage retain prognostic significance in a multivariate analysis. The median survival of patients with mutated IGVH genes, unmutated IGVH genes, and loss or mutation of the p53 gene regardless of IGVH gene status is 310, 119, and 47 months, respectively. These data should facilitate the design of new trials for the management of patients presenting with advanced disease or poor prognosis early stage disease.
Oscier
David G
DG
Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom. david.oscier@lineone.net
Gardiner
Anne C
AC
Mould
Sarah J
SJ
Glide
Sharron
S
Davis
Zadie A
ZA
Ibbotson
Rachel E
RE
Corcoran
Martin M
MM
Chapman
Robert M
RM
Thomas
Peter W
PW
Copplestone
J Adrian
JA
Orchard
Jenny A
JA
Hamblin
Terry J
TJ
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000704:Analysis of Variance; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015139:Blotting, Southern; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D008562:Membrane Glycoproteins; D009154:Mutation; D009244:NAD+ Nucleosidase / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012727:Sex Characteristics; D015996:Survival Rate; D014314:Trisomy
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1