Pediatric Mixed Phenotype Acute Leukemia-41 Cases Report

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia with a poor clinical outcome, defined by the blasts express antigens of more than one lineage. MPAL was also named as mixed lineage leukemia, bilineal leukemia, biphenotype leukemia historically. The properly diagnosis of MPAL is crucial for the treatment. The scoring system proposed by European Group for Immunological Characterization of Leukemia (EGIL) in 1995 was the first standard criteria to diagnose MPAL. In 2008, WHO proposed a new scoring criteria to define MPAL. But both of these two systems have their limitation.

We retrospectively analyzed 41 pediatric patients with mixed phenotype acute leukemia from 2000 to 2010 according to EGIL scoring system. All the 41 patients were reclassified according the 2008 WHO classification. Diagnosis, cytogenetics, immunophenotype, treatment and prognosis were analyzed.

There were 25 male and 16 female with the mean age of 8 years old. According to EGIL scoring system, the phenotype included T/myeloid (n=16), B/myeloid (n=13), T/B(n=11) and T/B/AML(n=1), respectively. Among the patients, there were 4 MPAL with t(9;22)(q34;q11), 5 with t(12;21)(p13;q22), 1 with inv(16)(p13;q22) and 1 with t(9;9). The overall complete remission (CR) rate was 47% treated by ALL regimen (n=19) and 17% by the AML+ALL combined therapy (n=6). MPAL with t(9;22)(q34;q11) showed poor response (4/4). MPAL with t(12;21)(p13;q22) had a good response to the treatment(4/5). Based on the 2008 WHO criteria, 24 of the 41 MPAL patients were reclassified as MPAL, including T/myeloid type(n=11), B/myeloid type(n=6), T/B(n=7). Three MPAL patients with t(12;21)(p13;q22) diagnosed by EGIL system were excluded by 2008 WHO criteria.

Our results suggest that MPAL is a poor outcome disease requiring more accurate classification based on genetic and gene classification. MPAL with t(9;22)(q34;q11) is a predictor of poor outcome. MPAL with t(12;21)(p13;q22) could be treated only by ALL regimen. MPAL with both lymphoid and myeloid markers appears to achieve a better CR rate if treated by ALL regimens alone than treated by ALL+AML combined regimens. Further studies are needed to determine a standard diagnosis and treatment approach for MAPL.

Zheng:Beijing Health System High-level Technical Personel Plan: Research Funding.