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. 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.