Reemphasis on lymphoblast L2 morphology as a poor prognostic factor in childhood acute lymphoblastic leukemia

In childhood acute lymphoblastic leukemia (ALL), the relationship between lymphoblast L1/L2 morphology and prognosis is controversial. According to some studies L2 morphology is associated with poor prognosis, whereas in others the association disappears after adjustment for other known risk factors.

We investigated the prognostic importance of lymphoblast L1/L2 morphology in childhood ALL treated with current Nordic ALL protocols in Finland. From the routine bone marrow (BM) aspirate and biopsy slides of 251 children with ALL diagnosed in 1990-1995, the blast cell morphology and early treatment responses were assessed blindly in a central review, using French-American-British (FAB) criteria with the Children's Cancer Group (CCG) modification.

L1 morphology (>90% L1) was found in 197 (80%) children and L2 (>/=10% L2) in 49 (20%). Early treatment response was poorer in L2 than in L1: >5% blasts in the marrow on day 15 were seen in 27% of L2 as opposed to 12% of L1 (P = 0.048). The 6-year event-free survival (EFS) in the study population was 75%, 76% in L1 and 70% in L2 (P = 0.34). In the group with white blood cell count (WBC) below 50 x 10(9)/liter at diagnosis, the L2 morphology was associated with inferior survival: 6-year EFS 74% in L2 and 84% in L1 (P = 0.07), with 6-year overall survival (OS) 81% vs. 91% (P = 0.035), respectively. L2 morphology was not associated with any other adverse prognostic factor analyzed.

With the intensive Nordic ALL protocols, lymphoblast L2 morphology is an independent poor prognostic factor, influencing both the early response to treatment and, in the low-WBC group, the ultimate outcome, and should be reemphasized in risk categorization of childhood ALL.