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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3913-3921
Prognostic Significance of Anaplastic Lymphoma Kinase (ALK) Protein
Expression in Adults With Anaplastic Large Cell Lymphoma
Randy D. Gascoyne,
Patricia Aoun,
Daniel Wu,
Mukesh Chhanabhai,
Brian F. Skinnider,
Timothy C. Greiner,
Stephan W. Morris,
Joseph M. Connors,
Julie M. Vose,
David S. Viswanatha,
Andrew Coldman, and
Dennis D. Weisenburger
From the Departments of Pathology and Laboratory Medicine, Medical
Oncology, and Epidemiology, British Columbia Cancer Agency, University
of British Columbia, Vancouver, BC, Canada; the University of Nebraska
Medical Center, Omaha, NE; and the Department of Experimental Oncology,
St Jude Children's Research Hospital, Memphis, TN.
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 5-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  60 years (P < .007), a normal serum
lactate dehydrogenase (LDH) (P < .00001), a good performance
status (Eastern Cooperative Oncology Group [ECOG] <2) (P < .03), 1 extranodal site of disease (P < .012), and an IPI score 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 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.
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