Outcome of the ALL-96 Protocol for Childhood ALL from the Kyushu-Yamaguchi Children’s Cancer Study Group.

Objective: We conducted a randomized study to compare the effectiveness of two maintenance regimens, namely the 6-MP/MTX-based regimen (A-arm) and the LSA2L2 type regimen (B-arm).

Patients and Methods: A total of 218 newly diagnosed patients between 1 and 15 years of age were enrolled from August 1996 to August 2002. The patients characteristics was as follows: median age, 5; T-cell/B-cell precursor phenotype, 22/196; median WBC, 8,100/μl (range, 600–809, 200). The high-risk group (HR) was defined as having a WBC of over 50,000/μl, a T-cell precursor phenotype, CNS disease, hepatosplenomegaly of more than 5 cm under the costal margin while the standard-risk group (SR) was defined as having no HR features. Any cases with t(9;22) and t(4;11) were excluded from the present protocol. After successful induction treatment, the patients received early intensification, consolidation and late intensification treatment. Before late intensification, the patients were randomly assigned to receive one of two maintenance regimens: the A-arm consisted of daily 6-MP with weekly MTX pulsed with DEX and VCR for 2 weeks irrespective of the risk group. The B-arm consisted of 4 blocks of 6-MP with CPM, 6-MP with CA, 6-MP with VCR and PSL, and intermediate-dose (ID)-MTX in the SR group, while in the HR group, high-dose CA was substituted for ID-MTX. The total treatment duration was 3 years. Eleven cases with t(9:22) and t(4;11), 5 with a disagreement to randomization, while the other 6 did not meet the eligibility criteria and thus were excluded from the protocol. As a result, 196 cases were evaluable (98 cases for each risk-group). Of these, 95 and 94 cases, excluding 7 who developed relapses before randomization, were assigned to the A and B-arms, respectively.

Results: CR was successfully achieved in 195 of 196 patients (99%). Relapse occurred in 36 cases (isolated BM, 30; others, 6). No toxic death was observed during the entire treatment period. The event-free survival (EFS) rates in all 196 eligible cases, SR and HR cases were 75.5±5.1 (SE) %, 88.1±3.6% and 62.5±7.5% (p=.0004), respectively. The EFS rates for SR were 86.8±5.6% in the A-arm and 90.6±4.6% in the B-arm (p=ns). In the HR cases, the EFS rate in the A-arm was tended to be superior to that in the B-arm (81.2±5.6% and 52.3±13.1%, p=.13).

Conclusion: No significant difference was observed in the EFS rates between the two maintenance regimens. However, the late adverse effects of each regimen should be carefully evaluated by a long-term follow-up of the patients.