Distinct Clinical and Cytogenetic Characteristics and Poor Prognosis in Children with Acute Erythroid Leukemia: A Report from the JPLSG AML-05 Study

BACKGROUND: Acute erythroid leukemia (AEL) is a rare subtype of acute myeloid leukemia (AML) that represents less than 5% of AML in children. However, its clinical picture is not fully understood.

PATIENTS & METHODS: We conducted a retrospective analysis on AEL using data from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (registered at http://www.umin.ac.jp/ctr/index.htm as UMIN000000511) in which patients were enrolled between 2006 and 2010. Morphological, immunophenotypic, cytogenetic, and molecular diagnoses were confirmed by the integrated prospective central diagnostic system.

RESULTS: Among the 443 children (age 0 to 18 years old at diagnosis) with de novo AML (acute promyelocytic leukemia and Down syndrome patients are excluded), ten AEL patients (2.2%) were identified. All the cases were classified as M6 in French-American-British classification (eight as M6a, one as M6b, and one as M6). Notably, 8 were classified as AML with myelodysplasia-related changes (5 with morphological dysplasia and 3 with myelodysplasia-related cytogenetic abnormalities) and 2 as AEL in World Health Organization classification (ver.4). There were 6 males and 4 females. Median age and leukocyte count at diagnosis was 3.5 years old (range, 1-15 years old) and 4.7 x 10⁹/L (1.1-16.1 x 10⁹/L), respectively. Cytogenetically, 3 had complex karyotype, 2 had monosomy 7, and 5 had normal karyotype. Molecular analysis showed one case with NRAS mutation, one with both mutated KIT and WT1, and one with MLL-PTD. No case was FLT3 -ITD positive. Eight cases achieved complete remission after initial induction but 3-year event-free survival and overall survival rates were 30.0% (SE 14.4%) and 41.1% (SE 17.5%), respectively.

CONCLUSIONS: AEL has distinct features such as high frequency of myelodysplasia- related features and poor risk cytogenetics. Because the outcome seems poor, further genetic analysis is required for development of effective novel therapy.