PROGNOSTIC-SIGNIFICANCE OF B-LINEAGE LEUKEMIC-CELL GROWTH IN SCID MICE - A CHILDRENS-CANCER-GROUP-STUDY

Primary leukemic cells isolated from children (N = 681) with newly dia gnosed 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 org ans. These SCID+ patients were somewhat more likely than SCID- patient s to be older than 10 years of age (p = 0.03) and have WBC counts >20, 000/mu L (p = 0.04), but the groups were similar with respect to all o ther presenting features. Event-free survival (EFS) outcome at 3 years of follow-up was similar for SCID+ patients compared with SCID- patie nts (79.2%, SD = 5.1% vs. 84.8%, SD = 2.8%; p = 0.20). Overall surviva l also was similar between the two groups (p = 0.93), This result was maintained within the subgroups of lower risk (N = 448) and higher ris k (N = 233) patients. However, there were trends for poorer outcome am ong patients whose cells caused overt leukemia in SCID mice and infilt rated 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 primar y leukemic cells in SCID mice was not a significant predictor of outco me for the aggregate population of B-lineage ALL patients, the majorit y of whom were low risk, treated according to contemporary intensive c hemotherapy programs of the CCG. However, development of disseminated overt leukemia and infiltration of SCID mouse skeletal muscle by prima ry leukemic cells from adjacent bone marrow may reflect a biologically more aggressive disease and identify patients at higher risk for trea tment failure.