Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group

Int J Hematol. 2015 Nov;102(5):602-10. doi: 10.1007/s12185-015-1869-y. Epub 2015 Sep 26.

Abstract

Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

Keywords: Acute lymphoblastic leukemia; Children; Hematopoietic stem cell transplantation; MLL.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Allografts
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Japan
  • Leukocyte Count
  • Male
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Survival Rate

Substances

  • MLL-AF4 fusion protein, human
  • Oncogene Proteins, Fusion
  • Myeloid-Lymphoid Leukemia Protein