Outcomes in Children and Adolescents with a Markedly Elevated White Blood Cell Count (>200,000) at Diagnosis of High Risk Acute Lymphoblastic Leukemia (ALL): A Report from the Children’s Oncology Group.

In prior studies, children and adolescents with markedly elevated (ME) WBC≥200,000 had a poor outcome. We examined the outcome of these patients enrolled on CCG l961 (n=250) and compared them to other patients with WBC<200,000 (n=1800). Criteria for CCG-1961 enrollment included age 1–9 years and WBC ≥ 50,000; or age ≥ 10 years with any WBC. Two-thirds of ME WBC patients were male; one third were ≥ 10 years of age, and 7% had CNS disease at diagnosis. Among patients with evaluable immunophenotypes (n=223), 46% had B precursor and 55% had T cell ALL. Event free survival (EFS) at 5 years for ME vs lower WBC patients was 60% and 73%, respectively (p<.0001). Survival (S) at 5 years was 73% vs 82% for ME and lower WBC patients, respectively (p=.0015). EFS for ME B precursor patients was 45% compared to 72% for lower WBC B precursor patients (p<.0001). EFS for ME and lower WBC T cell patients was 71% and 74%. On CCG 1961, rapid early response (RER) patients were randomized to receive stronger or standard intensity therapy and standard or longer intensification. Slow early response (SER) patients received increased intensity therapy and were randomized to receive sequential idarubicin/cyclophosphamide or weekly doxorubicin in intensification. All SER patients received 2 delayed intensifications. EFS for RER ME WBC patients (n=143) was 73% for stronger intensification and 60% for standard intensification. EFS for RER ME WBC was 72% for standard duration and 59% for longer duration intensification. EFS was 61% for SER patients (n=83) with no difference among regimens. Eleven of 103 B lineage ME WBC patients had Ph+ ALL of those there were 8 subsequent events. Patients with CNS 2 had significantly worse outcome (4 year EFS 52%) compared to patients with CNS 3 (4 year EFS 59%) or CNS 1(4 year EFS 68%) status at diagnosis, (p=.04). In conclusion, a ME WBC appears to have no prognostic significance for T cell patients while a ME WBC is highly prognostic for B precursor patients. Stronger intensification improves EFS for RER ME WBC patients as compared to standard intensification. Although the numbers are small, the magnitude of this difference is similar to the outcome of the entire study.