Prognostic implications of blast cell morphology in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group

Abstract

The Childrens Cancer Study Group (CCSG) has evaluated French-American-British (FAB) morphology in newly diagnosed children with acute lymphoblastic leukemia (ALL) since 1975. A modification of the FAB system was used in which individual lymphoblast cells were scored and designated as either L1 or L2 on the basis of distinctive morphologic characteristics. L1 ALL was defined as less than 10% L2 cells and greater than 90% L1 cells; L2 ALL was defined as greater than or equal to 10% L2 cells and less than 90% L1 cells. FAB morphology was an independent predictor of overall survival (P = 0.02) in CCSG-141 and a highly significant predictor of successful induction of complete remission and event-free survival in the CCSG-160 series (P = 0.00001). These studies involved nearly 3900 patients. Two concordance studies have been performed. In the first (1981) study, overall concordance between the FAB reference laboratory and member institutions was 76% using a two-category system (L1, non-L1), 86% for L1 cases, and 47% for non-L1 cases. In the second (1984) concordance study, the use of more stringent, semiquantitative definitions of L1 and L2 lymphoblasts did not improve overall (75%), L1 (89%), or non-L1 (46%) concordance. The results of reference laboratory classification more powerfully predicted event-free survival than did member institutions (P = 0.016 vs P = 0.125). Quality control factors (slide preparation, cellularity, staining quality, and discipline of the reviewer) did not influence concordance. These results justify the continued assignment of patients to protocols of the CCSG-100 series on the basis of the modified FAB classification. The biological significance of the FAB morphologic variants remains to be determined.