Frequency and prognostic significance of t(v;11q23)/KMT2A rearrangements in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols

Leuk Lymphoma. 2017 Jan;58(1):145-152. doi: 10.1080/10428194.2016.1177182. Epub 2016 Apr 27.

Abstract

The karyotype is an important predictor of outcome in acute lymphoblastic leukemia (ALL). Rearrangements of the 11q23 region involving the KMT2A gene confer an unfavorable prognosis. Forty-six adult ALL patients from the PETHEMA Group treated with risk-adapted protocols, with t(v;11q23) were selected for this study. Complete response (CR) was attained in 38 patients; 25 remained in CR after consolidation. Twelve (48%) received allogeneic hematopoietic stem cell transplantation (HSCT) and 13 delayed intensification and maintenance. The 5-year CR duration probability was 37% (95% CI, 19%-55%). A trend for a longer CR duration was observed in patients undergoing HSCT vs. those receiving chemotherapy. The 5-year overall survival (OS) probability was 20% (95% CI, 5%-35%). The OS was better, albeit not significant, in patients with a MRD level <0.1% after induction (39% [95% CI, 14%-64%] vs. 13% [95% CI, 0%-36%]). Specific treatment approaches are required to improve the outcome of patients with KMT2A-rearrangements.

Keywords: KMT2A/MLL; MRD; acute lymphoblastic leukemia.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Combined Modality Therapy
  • Female
  • Gene Frequency*
  • Gene Rearrangement*
  • Genetic Predisposition to Disease
  • Hematopoietic Stem Cell Transplantation / methods
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Translocation, Genetic*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase