Beneficial tyrosine kinase inhibitor therapy in a patient with relapsed BCR-ABL1-like acute lymphoblastic leukemia with CCDC88C-PDGFRB fusion

Int J Hematol. 2021 Feb;113(2):285-289. doi: 10.1007/s12185-020-03006-5. Epub 2020 Sep 19.

Abstract

BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a neoplasm of lymphoblasts committed to the B-cell lineage that lack the BCR-ABL1 translocation but show a pattern of gene expression very similar to that seen in ALL with BCR-ABL1 with poor prognosis. A 22-year-old female was diagnosed with common-B-cell-ALL positive for CD10, CD19, CD22, CD79a, CD34, HLA-DR, and TdT in January 2017, and achieved complete remission (CR) with induction therapy, followed by consolidation therapy and maintenance therapy. In March 2020, 6 months after the completion of maintenance therapy, she relapsed. Inotuzumab ozogamicin (IO) was administered, and on day 28, bone marrow evaluation showed a morphologic CR. She had an HLA-identical sibling, and transplantation in her 2nd CR was planned. Because her ALL had been identified as BCR-ABL1-like ALL with CCDC88C-PDGFRB fusion, she was treated with imatinib for 2 months accompanied by 2 intrathecal methotrexate therapies, and 1 course of L-asparaginase, vincristine, and prednisolone in an outpatient setting. MRD analysis revealed potent efficacy of 2 months imatinib therapy; IgH MRD decreased from 1 × 10-2 to 1 × 10-3, and CCDC88C-PDGFRB/104ABL from 37.3 to 0. It is earnestly desired that well-designed clinical trials of TKI in ABL class-mutant BCR-ABL1-like ALL be conducted in Japan.

Keywords: Acute lymphoblastic leukemia; BCR-ABL1-like; Imatinib; PDGFRB; Tyrosine kinase inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Biomarkers
  • Combined Modality Therapy
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Genetic Testing
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Microfilament Proteins / genetics*
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Neoplasm, Residual / diagnosis
  • Oncogene Proteins, Fusion / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Recurrence
  • Retreatment
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • CCDC88C protein, human
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • PDGFRB protein, human
  • Receptor, Platelet-Derived Growth Factor beta
  • Fusion Proteins, bcr-abl