Prognostic Relevance of CD10 in BCR-ABL Negative B-Cell Precursor Acute Lymphoblastic Leukemia Treated with High Dose Asparaginase.
Allan Jiang, Joseph Brandwein, Hong Chang. University Health Network, Toronto, Canada
Background: In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), absence of CD10 expression on leukemic blasts has traditionally been associated with translocations of the mixed lineage leukemia (MLL) gene at 11q23, and adverse outcome. However, the prognostic impact of CD10 negativity has yet to be fully established, particularly in the context of BCR-ABL negative B-ALL treated with a modified pediatric protocol with high dose asparaginase.
Design: We evaluated 126 consecutive patients diagnosed with de novo BCR-ABL negative B-ALL, and initiated on a modified Dana Farber Cancer Institute 91-01 pediatric protocol, from June 2000 to March 2010. Immunophenotypes, including CD10 and myeloid antigens, were determined by multiparameter flow cytometry. These phenotypes were correlated with MLL rearrangement status and clinical features.
Results: : Absence of CD10 expression was detected in 23 (18%) cases. Among these patients, 10 (53%) of 19 evaluable cases had MLL rearrangements; in contrast, none of the CD10-positive patients had MLL rearrangements (p=<0.001). CD10 negativity was also associated with leukocyte count above 30x109/L (p<0.001) and CD15 expression (p<0.001), but not with other clinical or laboratory characteristics. Patients lacking CD10 expression had shorter overall survival (OS, median 24.0 months vs. not reached, p=0.005) and relapse-free survival (RFS, median 20.2 months vs. not reached, p=0.003). MLL rearrangements were associated with inferior RFS (p=0.022) but not OS (p=0.19). Within the CD10-negative subgroup, patients with and without MLL rearrangements had comparable OS and RFS (p=0.29 and p=0.47 respectively). In addition, high leukocyte count (>30x109/L) also correlated with adverse OS (p=0.002) and RFS (p<0.001), while age over 45 was associated with shorter OS (p=0.009). CD34 and myeloid antigens did not correlate with survival. Multivariate analysis adjusting for higher leukocyte count, age > 45, and MLL rearrangements identified CD10 negativity as an independent predictor of inferior RFS (hazard ratio=5.7, p=0.004) whereas higher leukocyte count and older age were significant for an inferior OS (p=0.037 and p=0.005 respectively).
Conclusions: Our data suggest that the CD10 negativity has an adverse impact on BCR-ABL negative BCP-ALL treated with a high dose asparaginase-containing regimen, irrespective of MLL rearrangements. Further large prospective studies are warranted to confirm our observation and better characterize this high risk CD10-negative subgroup for risk stratification of BCP-ALL.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 152, Wednesday Morning