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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3931-3939
Value of Immunophenotype in Intensively Treated Adult Acute
Lymphoblastic Leukemia: Cancer and Leukemia Group B Study 8364
Myron S. Czuczman,
Richard K. Dodge,
Carleton C. Stewart,
Stanley
R. Frankel,
Frederick R. Davey,
Bayard L. Powell,
Ted P. Szatrowski,
Charles A. Schiffer,
Richard A. Larson, and
Clara D. Bloomfield
From the Roswell Park Cancer Institute, Buffalo, NY; the CALGB
Statistical Center, Durham, NC; Georgetown University Medical Center,
Washington, DC; State University of New York Health Science Center at
Syracuse, Syracuse, NY; Wake Forest University School of Medicine,
Winston-Salem, NC; New York Hospital-Cornell Medical Center, NY, NY;
Karmanos Cancer Institute, Wayne State University School of Medicine,
Detroit, MI; the University of Chicago, Chicago, IL; and Comprehensive
Cancer Center of the Ohio State University, Columbus, OH.
The prognostic value of immunophenotype in adult acute lymphoblastic
leukemia (ALL) has varied based on the methods used, surface markers
studied, and therapy administered. From April 1991 to September 1996, samples of leukemic marrow or blood from 259 eligible and evaluable
adult ALL patients entering dose-intensive Cancer and Leukemia Group B
(CALGB) front-line treatment protocols were prospectively studied for
immunophenotypic classification by multiparameter flow cytometry (MFC)
in a central laboratory. A B-lineage (B-LIN) phenotype was expressed in
79% of cases, with one third coexpressing myeloid antigens. A
T-lineage (T-LIN) phenotype was expressed in 17% of cases, with one
quarter coexpressing myeloid antigens. Since the advent of more
intensive CALGB therapy which incorporated cyclophosphamide and the
early use of L-asparaginase into the backbone of daunorubicin,
vincristine and prednisone, together with central nervous system
prophylaxis for adult ALL, no significant differences in response
rates, remission duration, or survival have been seen in those patients
coexpressing myeloid antigens. The T-LIN phenotype was associated with
younger age (P = .01), a higher male to female ratio
(P = .01), higher white blood cell count
(P = .001) and hemoglobin (P < .001) levels, presence of a mediastinal mass (P < .001), and longer
survival (P = .01) and disease-free survival (DFS)
(P = .01) when compared to patients with a B-LIN phenotype.
The 3-year probability of survival and DFS (95% confidence interval
[CI]) of T-LIN adult ALL was 0.62 (0.46 to 0.76) and 0.62 (0.44 to
0.77), respectively. Comparatively, the 3-year probability of survival
and DFS (95% CI) of B-LIN adult ALL was 0.42 (0.35 to 0.50) and 0.39 (0.31 to 0.47), respectively. The number of T markers expressed in
T-LIN ALL cases was shown to have prognostic significance. In
particular, patients expressing six or more markers compared with
patients expressing three or fewer markers had longer DFS
(P = .003) and survival (P = .004). The
presence of the Philadelphia chromosome was significantly associated
with B-LIN ALL cases which coexpressed CD19+,
CD34+, and CD10+ (49%;
P = .003), whereas the majority of t(4;11) cases were
CD19+, CD34+ but CD10 . The
knowledge gained from this study of MFC of a large number of patients
will permit a reduction in the number of antigens to be evaluated in
future studies. Overall, this should lead to cost savings without loss
of valuable information. A rational approach for future studies would
be to use four-color flow cytometry (instead of the current
three-color) to help further streamline the study of immunophenotype of
adult ALL by MFC.
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