Abstract
Abstract 3563
High levels of minimal residual disease (MRD) at the end of 4-weeks of multiagent induction chemotherapy have been shown to be associated with a high risk of subsequent relapse in pediatric patients (pts) with B-ALL. Published reports indicated that pediatric B-ALL pts with high end-induction MRD had event-free survival (EFS) rates < 50% when treated with standard chemotherapy.[Zhou, Blood 2007; Borowitz Blood 2008] Pts with high-risk (HR) cytogenetic abnormalities, such as low hypodiploidy and MLL gene rearrangements (MLL-R) also have a high relapse risk. On DFCI ALL Consortium Protocol 05–01, we piloted an intensified regimen for B-ALL pts with high end-induction MRD and/or HR cytogenetics.
Between 2005–2010, 482 evaluable pts aged 1–18 years with B-ALL were enrolled. Pts were initially classified as standard-risk (SR) or high-risk (HR) based on NCI age/WBC criteria. MRD was prospectively evaluated at the end of the 4-week induction phase via RQ-PCR analysis of IgH or TCR rearrangements. Results were reported as the ratio of copy numbers of target gene:GAPDH; a ratio >0.001 was considered high MRD. Pts with high MRD or HR cytogenetics (hypodiploidy with <45 chromosomes or MLL-R) were reclassified at the end of induction phase as very high risk (VHR), and received 2 additional chemotherapy cycles beginning at week 7 (cycle 1: cyclophosphamide, low-dose cytarabine, 6-MP; cycle 2: high-dose cytarabine, etoposide, dexamethasone, L-asparaginase), followed by the DFCI ALL Consortium HR consolidation phase, including 30 weeks of L-asparaginase and doxorubicin to a cumulative dose of 300 mg/m2. After consolidation, pts received a standard maintenance phase. Total duration of treatment was 25 months.
51 pts (11%) were classified as VHR, 25 of whom had been initially classified as SR and 26 as HR. 35 VHR pts had high end-induction MRD as the sole VHR criterion; 16 had HR cytogenetics. 9 pts relapsed (all marrow-involved) and 1 pt developed a secondary AML. There were no deaths in first remission. With median follow-up of 4.4 yrs, the 5-yr EFS (95% confidence interval) for all 51 VHR pts was 76% (60,87)[Figure 1] and 5-yr overall survival was 81% (60,92). The 5-yr EFS was 81% (59,90) for the 35 pts with high MRD.
Intensification of chemotherapy (without stem cell transplant) resulted in a relatively favorable EFS in VHR B-ALL pts (defined by the presence of either high end-induction MRD or HR cytogenetics). More pts and longer follow-up will be necessary to confirm these promising results.
Event-free survival for 51 very high risk B-ALL patients treated on DFCI ALL Consortium Protocol 05–01.
Event-free survival for 51 very high risk B-ALL patients treated on DFCI ALL Consortium Protocol 05–01.
No relevant conflicts of interest to declare.
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