Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma

被引:369
|
作者
Gascoyne, RD
Aoun, P
Wu, D
Chhanabhai, M
Skinnider, BF
Greiner, TC
Morris, SW
Connors, JM
Vose, JM
Viswanatha, DS
Coldman, A
Weisenburger, DD
机构
[1] Univ British Columbia, British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 1M9, Canada
[3] Univ British Columbia, British Columbia Canc Agcy, Dept Epidemiol, Vancouver, BC V5Z 1M9, Canada
[4] Univ Nebraska, Med Ctr, Omaha, NE USA
[5] St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA
关键词
D O I
10.1182/blood.V93.11.3913.411k22_3913_3921
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23; q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK(+) and ALK(-) groups, except that the ALK(+) patients were younger (median age, 30 v 61 years; P < .002). The ALK(+) cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK(+). The 5-year overall survival (OS) of the entire cohort was 65%. The B-year OS of the ALK(+) and ALK(-) cases was 79% and 46%, respectively (P < .0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK(+) cases and only 37% for the ALK- cases (P < .00001). Univariate analysis of the clinical features showed that age less than or equal to 60 years (P < .007), a normal serum lactate dehydrogenase (LDH) (P < .00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] <2) (P < .03), less than or equal to 1 extranodal site of disease (P < .012), and an IPI score less than or equal to 3 (P < .00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P <.00001), an IPI score of less than or equal to 3 (P < .0005), and ALK protein expression (P < .005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL. (C) 1999 by The American Society of Hematology.
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页码:3913 / 3921
页数:9
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