title: Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia.
abstract: Sixty-two infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia (MLL-r ALL) were treated with the MLL03 protocol of the Japanese Pediatric Leukemia/Lymphoma Study Group: short-course intensive chemotherapy followed by early allogeneic hematopoietic stem cell transplantation (HSCT) within 4 months of the initial induction. The 4-year event-free survival and overall survival rates were 43.2% (95% confidence interval (CI)=30.7-55.1%) and 67.2% (53.8-77.4%), respectively. A univariate analysis showed younger age (<90 days at diagnosis), central nervous system disease and poor response to initial prednisolone therapy significantly associated with poor prognosis (P<0.05). In a multivariate analysis, younger age at diagnosis tended to be associated with poor outcome (hazard ratio=1.969; 95% CI=0.903-4.291; P=0.088). Although the strategy of early use of HSCT effectively prevented early relapse and was feasible for infants with MLL-r ALL, the fact that substantial number of patients still relapsed even though transplanted in their first remission indicates the limited efficacy of allogeneic HSCT for infants with MLL-r ALL. Considering the risk of severe late effects, indications for HSCT should be restricted to specific subgroups with poor risk factors. An alternative approach incorporating molecular-targeted drugs should be established.
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Aichi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Moriya Saito
authors.affiliation: Department of Nutritional Science, Faculty of Psychological and Physical Science, Aichi Gakuin University, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Osaka University, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyamura
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirayama
authors.affiliation: Department of Pediatrics, Aomori Prefectural Central Hospital, Aomori, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ogawa
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Aichi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, University of Yamanashi, Yamanashi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugita
authors.affiliation: Department of Control and Treatment of Infectious Disease, Chiba University Hospital, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Takita
authors.affiliation: Department of Pediatrics, Nara Medical University, Nara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takeshita
authors.affiliation: Department of Pediatrics, Ama Municipal Hospital, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsurusawa
authors.affiliation: Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Aichi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mizutani
authors.affiliation: Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Ishii
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D018380:Hematopoietic Stem Cell Transplantation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy*; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011239:Prednisolone; D011495:Histone-Lysine N-Methyltransferase