title: Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: A report from the Japan Infant Leukemia Study Group.
abstract: 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
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan. dtomizawa.ped@tmd.ac.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirayama
authors.forename: Takako
authors.initials: T
authors.lastname: Miyamura
authors.forename: Michiki
authors.initials: M
authors.lastname: Hatanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015321:Gene Rearrangement; D018380:Hematopoietic Stem Cell Transplantation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase