Prognostic Significance of B-Lineage Leukemic Cell Growth in SCID Mice: A Children's Cancer Group Study

Abstract

Primary leukemic cells isolated from children (N=681) with newly diagnosed B-lineage ALL enrolled on risk-adjusted treatment protocols of the Children's Cancer Group (CCG) were injected via the tail vein into 7-10 week old SCID mice. Leukemic cells from 104 of 681 patients (15.3%) were able to engraft and proliferate in one or more SCID mouse organs. These SCID+ patients were somewhat more likely than SCID− patients to be older than 10 years of age (p=0.03) and have WBC counts >20,000/μL (p=0.04), but the groups were similar with respect to all other presenting features. Event-free survival (EFS) outcome at 3 years of follow-up was similar for SCID+ patients compared with SCID− patients (79.2%, SD=5.1% vs. 84.8%, SD=2.8%; p=0.20). Overall survival also was similar between the two groups (p=0.93). This result was maintained within the subgroups of lower risk (N=448) and higher risk (N=233) patients. However, there were trends for poorer outcome among patients whose cells caused overt leukemia in SCID mice and infiltrated either 6 or more organs (p=0.03), skeletal muscle (p=0.0003), kidney (p=0.05), or spleen (p=0.06). Thus, engraftment of primary leukemic cells in SCID mice was not a significant predictor of outcome for the aggregate population of B-lineage ALL patients, the majority of whom were low risk, treated according to contemporary intensive chemotherapy programs of the CCG. However, development of disseminated overt leukemia and infiltration of SCID mouse skeletal muscle by primary leukemic cells from adjacent bone marrow may reflect a biologically more aggressive disease and identify patients at higher risk for treatment failure.