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 MILL 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. Pediatr Blood Cancer 2009;52:808-813. (C) 2009 Wiley-Liss, Inc.