Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: Cancer and Leukemia Group B study 8364

The prognostic value of immunophenotype in adult acute lymphoblastic leukem ia (ALL) has varied based on the methods used, surface markers studied, and therapy administered. From April 1991 to September 1996, samples of leukem ic marrow or blood from 259 eligible and evaluable adult ALL patients enter ing dose-intensive Cancer and Leukemia Group B (CALGB) front-line treatment protocols were prospectively studied for immunophenotypic classification b y multiparameter flow cytometry (MFC) in a central laboratory. A B-lineage (B-LIN) phenotype was expressed in 79% of cases, with one third coexpressin g myeloid antigens. A T-lineage (T-LIN) phenotype was expressed in 17% of c ases, with one quarter coexpressing myeloid antigens. Since the advent of m ore intensive CALGB therapy which incorporated cyclophosphamide and the ear ly 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 surv ival have been seen in those patients coexpressing myeloid antigens. The T- LIN phenotype was associated with younger age (P = .01), a higher male to f emale ratio (P = .01), higher white blood cell count (P = .001) and hemoglo bin (P < .001) levels, presence of a mediastinal mass (P < .001), and longe r survival (P = .01) and disease- B-LIN phenotype. The I-year probability o f 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 0.4 2 (0.35 to 0.50) and 0.39 (0.31 to 0.47), respectively. The number of T mar kers expressed in T-LIN ALL cases was shown to have prognostic significance . In particular, patients expressing six or more markers compared with pati ents expressing three or fewer markers had longer DFS (P = .003) and surviv al (P = .004). The presence of the Philadelphia chromosome was significantl y associated with B-LIN ALL cases which coexpressed CD19(+), CD34(+), and C D10(+) (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 larg e number of patients will permit a reduction in the number of antigens to b e evaluated in future studies. Overall, this should lead to cost savings wi thout loss of valuable information. A rational approach for future studies would be to use four-color flow cytometry (instead of the current three-col or) to help further streamline the study of immunophenotype of adult ALL by MFC. (C) 1999 by The American Society of Hematology.