Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: Report from the Japanese Children's Cancer and Leukemia Study Group

Background Prevention of central nervous system (CNS) leukemia by early int roduction of therapy to this sanctuary site is an essential component of mo dern treatment strategy for acute lymphoblastic leukemia (ALL). However, th e optimal form of preventive CNS therapy remains debatable. Procedure. To a ddress this issue, we evaluated the efficacy of CNS preventive therapy for 572 children with ALL who achieved complete remission in the Children's Can cer and Leukemia Study Group (CCLSG) ALL874 (1987-1990) and ALL911 (1991-19 93) studies. They received risk-directed therapy based on age and leukocyte count. In the ALL 874 study, the non-high-risk (low-risk [LR] + intermedia te risk [IRI]) patients were randomly assigned to the conventional cranial irradiation (CRT) regimen (L874A and 1874A) and the high-dose methotrexate (HDMTX) regimen without CRT (L874B and 1874B). The former patients received 18-Gy CRT plus 3 doses of intrathecal (IT) MTX and the latter patients rec eived 3 courses of HDMTX at 2 g/m(2) plus 13 doses of ITMTX (L874B) or 4 co urses of HDMTX at 4.5 g/m(2) plus 1 dose of ITMTX (1874B). Results. The 7-y ear probabilities (+/- SE) of CNS relapse-free survival were 97.3% +/- 2.6% (L874A, n = 41)vs. 90.3% +/- 5.3% (L874B, n = 39) (P= 0.25) in the LR pati ents, and 100% (1874A, n = 55) vs. 78.5% +/- 6.5% (1874B, n = 54) (P= 0.002 ) in the IR patients. The corresponding disease-free survival (DFS) rates w ere 79.4% +/- 6.5% vs. 74.4% +/- 7.3% (P= 0.62) in the LR group and 63.3% /- 6.8% vs. 58.3% +/- 7.2% (P= 0.66) in the IR group. Thus, the HDMTX regim en could not provide better protection of CNS relapse as compared with the CRT regimen, although their overall efficacy was not significantly differen t. In the ALL 911 study, intensive systemic chemotherapy with extended i,t, injections of MTX plus cytarabine achieved a high CNS relapse-free surviva l (98% +/- 1.9% at 7 years) and a favorable DFS (85.5% +/- 5% at 7 years) i n the IR patients. The patients in the high-risk (HR) group in both ALL874 and ALL911 studies received the 18-Gy or 24-Gy CRT with intensive systemic chemotherapy. Their 7-year probabilities of CNS relapse-free survival range d from 88% to 95%, among which the T-ALL patients had a risk of CNS leukemi a, which was 3-4 times higher compared with B-precursor ALL patients. Concl usions. These results indicate that long-term intrathecal CNS prophylaxis a s well as appropriate systemic therapy for the non-high-risk patients can p rovide protection against CNS relapse equivalent to that provided by crania l irradiation. Med. Pediatr. Oncol. 32: 259-266, 1999. (C) 1999 Wiley-Liss, Inc.