Treatment of High Risk T-Cell Acute Lymphoblastic Leukemia (T-ALL): Comparison of Recent Experience of the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG).

Abstract

Recent CCG and POG treatment stategies for patients with T-ALL are significantly different. POG treats T-ALL patients on a separate protocol from that used for B precursor ALL (B-ALL) while CCG treats T-ALL patients on the same protocols utilized for B-ALL patients with protocol assignment determined by the NCI risk classification. We recently reviewed the outcome of patients with T-ALL and high-risk features (age ≥ 10 years and/or initial WBC > 50,000/ul) treated on either the CCG-1961 or POG-9404 clinical trials. POG utilized an intensive anthracycline based multidrug regimen based on the DFCI treatment program and randomized patients at registration to receive or not receive additional high dose methotrexate(HDMTX) with leucovorin rescue. All patients received cranial irradiation (CRT). CCG therapy for high risk T-ALL was based on CCG modified BFM(S-BFM) and Augmented BFM(A-BFM). Patients with <25% blasts on day 7 bone marrow(RER) who achieved remission were randomized in a 2X2 design to standard or augmented intensity and standard duration(1 interim maintenance(IM) and 1 delayed intensification(DI) phase or prolonged duration (2 IM and DI phases). Only RER patients with CNS-3 status received CRT. Patients with a slow response(SER) to induction therapy received A-BFM therapy +/− idarubicin/cyclophosphamide courses during DI phases. All SER patients received CRT. In the POG trial, HDMTX produced a significant improvement in event free survival (EFS). In the CCG trial, for RER patients, augmented intensity regimens produced a better EFS than standard intensity regimens. There was no difference in outcome for patients receiving standard or prolonged duration therapy. Thus we compared the high dose MTX arm from POG 9404 to a composite EFS result for CCG l961 based on induction failure/toxic death rate, augmented intensity therapy(1 or 2 DI phases) for RER patients and A-BFM therapy for SER patients. POG 9404, (opened 6/1996; closed 9/2001) and enrolled 363 T-ALL patients, with 77% having high risk features of which 155 were randomized to HDMTX arms. 5 yr EFS for patients on these arms was 75% and overall survival (S) of 84%. CCG 1961(opened 11/1996;closed 5/2002) entered 2077 patients of which 410 had T-cell disease with 263 RERs. The projected composite 5 year EFS and S estimated for high risk T-ALL patients treated on CCG l961 was 76.9% and 82.5% respectively. Isolated CNS relapse accounted for approximately 2/3 of the relapses in RER patients patients.CNS 3 patients treated on 9404 demonstrated 75% 5 yr EFS as compared to 82% for patients on 1961. Outcome for higher risk T-ALL patients treated by POG and CCG were quite similar. However, the BFM based strategy utilizes significantly less anthracycline and appears to produce a lower rate of bone marrow relapse. We postulate that incorporating low dose cranial RT(1200 cGy) will significantly reduce the incidence of CNS relapse and improve the overall EFS rate. Therefore, COG will utilize an augmented intensity BFM backbone for the first T-ALL protocol.