Chronic myelogenous leukemia (CML) is a malignant myeloid disorder characterized by the presence of a distinctive cytogenetic abnormality known as the Philadelphia chromosome.

Exposure to ionizing radiation is the only known risk factor with median presentation at age >50 years old.

Three phases of the disorder are chronic, accelerated and blast.

Choice of therapy is influenced by age, availability of a donor, comorbidities and phase of CML.

Hematopoietic Stem Cell Transplantation (HSCT)

  • Patients are first treated with a preparative or conditioning regimen (eg chemotherapy or radiation therapy or both) followed by infusion of hematopoietic progenitor/stem cells
  • Parameters for HCT application depends on the patient’s disease and stage of the disease, cell donor and the source of the progenitor cells

Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HCT)

  • The indications and outcomes of allo-HCT will depend on the age and comorbidities of the patient, donor type and transplant center
  • Progenitor cells are collected from healthy persons and are used to treat hematologic neoplasms, nonmalignant marrow disorders (eg acquired and inherited), and inborn errors of metabolism
  • First-line treatment option for patients diagnosed with BP-CML at initial evaluation
  • May be considered in CP-CML patients deemed cytogenetically and molecularly unresponsive to multiple TKI therapy or those with T315I mutation unresponsive to Ponatinib therapy
  • May be considered in patients with AP unresponsive to TKI therapy, BP following induction of TKI, relapsed disease, resistant to multiple TKIs and intolerant to TKI

Monitoring Response with Allo-HCT

  • A qPCR assay that is positive ≥18 months after transplant is associated with a lower risk of relapse compared to those with positive qPCR assay at 6-12 months post-transplant
  • In a patient with prior accelerated or blast phase CML who attained complete cytogenetic response (CCyR) and is negative for BCR-ABL1, TKI therapy for at least 1 year should be considered
  • In a patient who attained CCyR who is positive for BCR-ABL1 or patients not in CCyR or is in relapse, options to undergo treatment with TKIs with or without donor lymphocyte infusion (DLI) or Omacetaxine, or may be enrolled in a clinical trial should be discussed

Management of Post-transplant Relapse

  • Donor lymphocyte infusion (DLI)
    • Induces effective durable molecular remissions in patients with relapsed CML following allo-HCT
      • The probability of survival at 3 years is better
    • More effective in patients with chronic phase relapse
    • Complications such as graft-vs-host disease (GVHD), susceptibility to infections and immunosuppression may develop
    • Ways on how to reduce the incidence of GVHD:
      • Improve the methods that detects BCR-ABL1 transcripts
      • Develop reduced-intensity conditioning regimens
      • Modify the delivery of lymphocytes with the depletion of CD8+ cells
      • Escalate cell dosage regimen
      • Very low-dose DLI and IFN-alpha combination may help reduce GVHD
  • Imatinib
    • Induces durable remissions in patients with relapse in all phases of CML following allo-HCT
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