Nation-Wide Survey of Infant Leukemia in Japan: A Report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).

Infant leukemia consists of wide spectrum of disease phenotype which includes acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lineage leukemia, and has unique biological and clinical features. However, there are few studies which have focused on its diversity from the cross-sectional view of this specific age group. We here conducted a nation-wide survey to analyze the disease distribution, characteristics, clinical courses, and outcomes of these patients in Japan. Questionnaires were sent to 170 institutions participating in the JPLSG which covers more than 95% of the hospitals in Japan, and total of 225 cases with infant leukemia and related disorders aged less than 24 months at onset who were diagnosed between 2004 and 2007 were registered. Median age at onset was 12 months, ranged from 0 to 22 months. No gender differences were observed (male, 118 cases; female, 107 cases). Thirty-nine were diagnosed as ALL with positive MLL gene rearrangements (MLL-R ALL), 74 as ALL with germline MLL (MLL-G ALL), 83 as AML, 9 as mixed lineage leukemia, and 20 as other disorders. In MLL-R ALL group, the frequency of t(4;11) was high in patients of <12 months of age (18/29 cases), whereas hyperdiploidy was detected in 20% of cases of MLL-G ALL group (12/61 cases). In AML, positive MLL gene rearrangements were detected in only 15% (13/83 cases), while t(1;22)(p13q13) or OTT-MAL was detected in 4 cases. Regardless of disease groups, early infant group of <6 months of age showed poor prognosis compared with other age groups. Particularly, all cases of ALL diagnosed at <4 weeks after birth harbored MLL gene rearrangements and either died or relapsed, indicating that more appropriate strategy is needed to improve the outcome for this specific group. Patients with MLL-G ALL less than 12 months old showed a favorable prognosis compared to those with MLL-R ALL. In AML, majority of cases were myelomonocytic/monocytic leukemia (M4/M5) or megakaryoblastic leukemia (M7), and showed favorable outcome. In conclusion, infant leukemia is still a challenging disease harboring diverse features, therefore, it is necessary to keep on-going the prospective trials, to register and follow-up these cases systematically and to standardize its treatment including supportive cares, especially for those with younger age onset.