Prognostic Factors in CD10 Negative Precursor B-Cell Acute Lymphoblastic Leukemia in Children: Data from Three Consecutive Trials ALL-BFM 86, 90, and 95.

The overall unfavorable prognosis of CD10 negative (CD10⁻) precursor B-cell acute lymphoblastic leukemia (BCP-ALL) is well known. We analyzed 4473 pediatric patients (pts) <18 years (y) with BCP-ALL and immunophenotyping of CD10 enrolled from 1986 to 2000 in three consecutive ALL-BFM trials to explore prognostic factors in the CD10⁻ subset. CD10 negativity was defined by CD10 expression in <20% of blasts. 233 pts (5.2%) were CD10⁻. In comparison to CD10 positive (CD10⁺) BCP-ALL pts, CD10⁻ pts comprised more infants (age <1y 34% vs. 1%, p(X²)<0.001), more cases with hyperleukocytosis (WBC ≥100/nl 43% vs. 6%, p<0.001), more CNS involvement (CNS positive 10% vs. 2%; p<0.001) and an impaired treatment response (prednisone poor response (PPR) 22% vs. 5%, p<0.001; induction failure 6% vs. 1%, p<0.001). Estimated probability of 5 years event free survival (5y-pEFS) was significantly lower in pts with CD10⁻ as compared to CD10⁺ BCP-ALL (49±3% vs 81±0.6%, p(log-rank)<0.001). Cox regression analysis including age, WBC, prednisone response (PR) and MLL/AF4 status as covariables revealed CD10 negativity as independent prognostic factor (RR 1.5, 95% confidence interval (CI) 1.1–2.1, p=0.01). Further analyses were performed within the CD10⁻ group: 83% of infants and 60% of pts ≥1y were successfully analyzed for MLL/AF4. MLL/AF4 was detected in 55% of pts <1y and 27% of pts ≥1y. The well known risk factors for BCP-ALL (sex, age, WBC, CNS involvement, MLL/AF4 and PPR) also had prognostic impact within the CD10⁻ group:

Out of a number of immunophenotypic markers, analyzed at different expression cut-off points, CD24 at missing or weak expression of <40% and CD65 at high expression of ≥40% were significantly correlated with unfavorable clinical characteristics and worse outcome within the CD10⁻ group. Significant correlation with PR could only be demonstrated for expression of CD24, which is presumed to act as negative regulator in B-cell development through mediation of apoptosis.

Including age, WBC, PR and MLL/AF4 status as covariables, out of the analyzed markers only CD65 proved to be an independent prognostic factor in CD10⁻ BCP-ALL (Cox regression analysis: RR 1.5, 95% CI 1.1–2.9, p=0.018). The identification of additional prognosis associated immunophenotypic markers may contribute to further refinement of treatment strategies for CD10⁻ BCP-ALL pts.