Contemporary treatment methods of adult patients with BCR/ABL1 positive chronic myeloid leukemia

Vnitr Lek. 2020 Summer;66(4):214-224.

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia that is characterised by Philadelphia chromosome (Ph1 chromosome) and/or fusion gene BCR-ABL1 in bone marrow. Interpheron α and bone marrow transplantation used to be the main treatment modalities for patients with CML 20 years ago. Due to the introduction of imatinib mesylate since the year 2000 the outcome of CML patients has dramatically improved. The survival of both younger and elderly patients in the case of an optimal response has been prolonged and currently is close to survival of healthy population. Although, one third of patients does not respond well to first line imatinib and needs to change the treatment to second line tyrosine kinase inhibitors (TKI: bosutinib, dasatinib and nilotinib). Younger patients without cardiologic and metabolic disorders and those with poor risk profile score may have benefit from TKI of 2nd generation as a 1st line treatment option with the aim of reaching deeper molecular response and the chance of treatment free remission (TFR) in future. By older patients with severe comorbidities and in patients with good risk profile score imatinib as a 1st line treatment option can be used. For patients who are resistant simultaneously to 2nd generation TKI and for patients with mutation T315I ponatinib - TKI of 3rd generation can be used effectively. Intolerance and toxicity of TKI´s are the main barriers of effective CML treatment. TKI selection for each patient should be individual. Patient´s cooperation with medical team is crucial and inevitable in long time treatment process. The chance for TFR has become feasible for approximately 40-60 % CML patients in deep and durable molecular remission and represents a further important milestone in the management of CML patients.

Keywords: bosutinib; chronic myeloid leukemia; dasatinib; hematopoietic stem cell transplantation; imatinib; nilotinib; ponatinib; remission; tyrosine kinase inhibitors.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents* / therapeutic use
  • Dasatinib / therapeutic use
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / therapeutic use
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Dasatinib