Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study

Br J Haematol. 2021 Mar;192(5):832-842. doi: 10.1111/bjh.17336. Epub 2021 Feb 2.

Abstract

In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16-75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3-CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow-up was 5·48 years; five-year survival rate was 17%. Patients with s-/t-AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo-HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo-HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo-HCT in CR1 was effective in de novo AML but not in patients with s-AML/t-AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo-HCT performed in CR1.

Keywords: acute myeloid leukaemia; allogeneic haematopoietic cell transplantation; outcome; t(8;16)(p11;p13)/MYST3-CREBBP; whole-genome sequencing.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormal Karyotype
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chromosomes, Human, Pair 16 / ultrastructure*
  • Chromosomes, Human, Pair 8 / ultrastructure*
  • Combined Modality Therapy
  • Consolidation Chemotherapy
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • International Cooperation
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / epidemiology
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / epidemiology
  • Oncogene Proteins, Fusion / genetics
  • Remission Induction
  • Survival Analysis
  • Translocation, Genetic*
  • Whole Genome Sequencing

Substances

  • Oncogene Proteins, Fusion