Results of PETHEMA LAL-BR-01 Protocol for Low-Risk (LR) Acute Lymphoblastic Leukemia (ALL) In Children

Children with ALL and low-risk (LR) features have a survival over 80%. The study of minimal residual disease (MRD) is an additional tool for best risk definition and for optimal selection of post-remission treatment. The results of PETHEMA LAL-BR-01 for low-risk childhood ALL (LR-ALL) including sequential MRD evaluation are presented.

Baseline LR-ALL criteria included age 1–9 yr., B-precursor ALL, WBC count <50×10⁹/L, no CNS involvement and absence of hypodiploidy, t(9;22) (BCR-ABL) or 11q23 (MLL) rearrangements. Induction therapy included VCR, DNR, PDN, ASP and CPM (4 weeks), followed by reinduction-consolidation (R-C), consolidation with intensification (C-I) (both including HD-MTX and HD-ARAC among other drugs), maintenance (MP and MTX) with reinductions (with VCR, PDN and ASP)(M-R) during the first yr., and maintenance (M) without reinductions during the second year. CNS prophylaxis consisted of triple intrathecal therapy (MTX, ARA-C and hydrocortisone). Patients with slow cytologic response (>1× 10⁹ peripheral blood blasts/L on day 8 or >20% bone marrow blasts on day 14), or MRD>0.1% after induction, or MRD >0.01% after R-C or at the 1^st or 1.5 yr of therapy were moved to a high-risk (HR) protocol.

By April 2010, 176 pts (mean (SD) age 4 (2) yr., 96 males) were evaluable. Baseline ALL characteristics: WBC 8 (SD 6) ×10⁹/L, common ALL 144 (35%), pre-B 30 (17%), hyperdiploidy >50 chromosomes 32 (19%), TEL/AML1 40/140 (29%), normal karyotype 41(24%). Treatment response (172 pts): induction death 2 (infection in both), abandon 2, and complete response (CR) 168 (98%). Five patients were moved to a HR protocol because of slow cytologic response (n=4) or MRD >0.1% at the end of induction (n=1). During consolidation and maintenance 4 pts relapsed and 4 were moved to HR protocol because of MRD>0.01%. Out of 104 pts who completed therapy, 4 relapsed. Seven out of 9 patients moved to the HR protocol (including the 5 pts transferred due to high MRD level) are in first CR and the remaining 2 relapsed. With a median follow-up of 3 (0.1-8.3) yr, 6-yr probabilities of CR duration, overall survival and event-free survival were 92±5%, 97±3% y 87±5%, respectively. The most frequent toxicity was due to infections, and was observed in all phases of the protocol, especially in induction. Dose modifications were documented in 6% of induction cycles, 15% of R-C, and 18% of C-I, in 27% of the patients during M-R and in 25% of the patients during M phase.

1. Most LR-ALL pts achieved a durable CR. 2. Most patients shifted to a HR protocol on the basis of slow response to treatment or MRD positivity maintained CR with HR protocol. 3. Toxicity was acceptable, although frequent dose reductions were required. Supported in part by grants P-EF09 from FJC and RD06/0020/1056 from RTICC.

No relevant conflicts of interest to declare.