Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: A report from the Japan Infant Leukemia Study Group.

BACKGROUND: Despite the poor outcome of recurrent or refractory acute lymphoblastic leukemia (ALL) in infants with MLL gene rearrangement, few studies have focused on this specific group. We conducted a retrospective analysis of infants with recurrent or refractory ALL from two previous consecutive Japanese studies to clarify the characteristics and prognostic factors among these patients

PROCEDURE: All recurrent or refractory ALL infants with MLL gene rearrangement (MLL-R) who were registered in two consecutive Japanese nation-wide multicentric trials (MLL96 and MLL98; between 1995 and 2001) were eligible for the study.

RESULTS: Among 80 MLL-R ALL infants, 34 cases of recurrence and 5 induction failures occurred. The median duration of first remission was 5 months (range, 0-28 months). All patients underwent various salvage chemotherapies; remission was achieved in 40.5% (15/37). A total of 23 patients received subsequent hematopoietic stem cell transplantations (HSCT): 9 in remission, 12 without remission, and 2 with unknown status. With median follow-up period of 5.5 years, the 5-year overall survival (OS) rate after the second-line treatment was 25.6% +/- 6.9%. Young age (<3 months) and central nervous system involvement at initial diagnosis were associated with poor outcome; however, failure to achieve remission after salvage therapy was the sole independent poor prognostic factor in multivariate analysis (P = 0.01).

CONCLUSIONS: The prognosis of infants with recurrent or refractory MLL-R ALL is extremely poor despite alternative treatments including HSCT; therefore, it is necessary to develop novel treatment strategies.