TREATMENT OF HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA IN CHILDREN USINGTHE AL851 AND ALHR88 PROTOCOLS - A REPORT FROM THE KYUSHU-YAMAGUCHI CHILDRENS-CANCER-STUDY-GROUP IN JAPAN

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protoc ols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patien ts received induction therapy consisting of vincristine (VCR), prednis olone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the AL HR88 protocol, the patients whose blasts in the bone marrow (BM) were greater than or equal to 25% on day 14 of induction therapy and who we re classified into T-cell type received additional cytosine arabinosid e (AraC). After consolidation with intermediate-dose methotrexate (MTX ), reinduction therapy including VCR, dexamethasone, and adriamycin fo llowed by high-dose AraC was done for all patients. Intrathecal MTX an d 24Gy of cranial irradiation were used to prevent central nervous sys tem leukemia. A maintenance therapy consisting of 6-mercaptopurine, cy clophosphamide,, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (9 2.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free su rvival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of le ukemic cells by FAB classification (P = 0.009), the chromosomal abnorm ality (P = 0.001) and high residual leukemic cells in BM (greater than or equal to 25%) on day 14 of induction therapy (P < 0.001). Taking t hese factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL. (C) 1996 Wiley-Liss, Inc .