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Blood, Vol. 93 No. 8 (April 15), 1999:
pp. 2688-2696
Adverse Effects of Activated Cytotoxic T Lymphocytes on the Clinical
Outcome of Nodal Anaplastic Large Cell Lymphoma
Rosita L. ten Berge,
Danny F. Dukers,
Joost J. Oudejans,
Karen Pulford,
Gert J. Ossenkoppele,
Daphne de Jong,
Jo F.M.M. Miseré, and
Chris J.L.M. Meijer
From the Departments of Pathology and Haematology, University
Hospital Vrije Universiteit, Amsterdam, The Netherlands; the Department
of Cellular Science, John Radcliffe Hospital, Oxford, United Kingdom;
the Department of Pathology, The Netherlands Cancer Institute,
Amsterdam, The Netherlands; and the Department of Pathology, St.
Elisabeth Hospital, Tilburg, The Netherlands.
Systemic (nodal) anaplastic large cell lymphoma (ALCL) is a subgroup
of T-cell non-Hodgkin's lymphomas with a relatively favorable clinical
outcome. Part of systemic ALCLs harbor a genetic aberration (usually
the t(2;5)(p23;q35) translocation) containing the anaplastic lymphoma
kinase (ALK) gene at 2p23, which results in aberrant expression of the
ALK protein. Recently, we have shown that the presence of high
percentages of activated cytotoxic T lymphocytes (CTLs) in tumor biopsy
specimens of Hodgkin's disease (HD) is associated with a poor
prognosis. In the present study, we investigated the prognostic value
of percentages of activated CTLs in combination with ALK expression in
primary nodal ALCL. Primary nodal biopsies of 42 patients with ALCL
were investigated for the percentage of activated CTLs (quantified
using Q-PRODIT) and the expression of ALK by
immunohistochemistry using monoclonal antibodies (MoAbs) directed
against T-cell antigen granzyme B (GrB) and ALK, respectively. These
parameters were evaluated for their predictive value regarding progression-free and overall survival time. The presence of a high
percentage of activated CTLs (ie,  15%) was found to be an unfavorable prognostic marker. In combination with a lack of ALK expression, it was possible to identify a group of patients with a very
poor prognosis. In this group, 13 of 16 patients died within 2 years as
a result of the disease. Of the remaining 26 patients, only three (all
ALK negative) died (P < .0001). Furthermore, the percentage
of activated CTLs combined with ALK status appeared to be of stronger
prognostic value than the International Prognostic Index (IPI). We
conclude that a high percentage of activated CTLs present in biopsy
material of patients with primary nodal ALCL is a strong indicator for
an unfavorable clinical outcome. The combination of ALK expression and
percentage of activated CTLs appears to be more sensitive than the IPI
in identifying a group of patients with a highly unfavorable clinical
outcome who may be eligible for alternative (high dose) therapy schemes.
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