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.

Surgical Intervention

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

Allogeneic hematopoietic stem cell transplantation (Allo-HCT)

  • The indications & outcomes of allo-HCT will depend on the age & comorbidities of the patient, donor type &transplant center
  • Progenitor cells are collected from healthy persons & are used to treat hematologic neoplasms, nonmalignant marrow disorders (eg acquired & inherited), & inborn errors of metabolism
  • May be considered in patients with AP unresponsive to TKI therapy, BP following induction of TKI, relapseddisease, resistant to multiple TKIs & intolerant to TKI

Monitoring response with allo-HCT

  • In patients who attained a BCR-ABL1 0.1%-<1% (IS), patients are monitored using the QPCR-IS every 3 months for 2 years then 3-6 months thereafter
    • A QPCR assay that is positive at a much later point after transplant is associated with a lower risk of relapse
    • On follow-up, the patient may have TKIs or Omacetaxine, donor lymphocyte infusion (DLI) or Interferon/Peginterferon, or may be enrolled in a clinical trial
  • In patients who did not have a CCyR or had a relapse, the withdrawal of immune suppression should be monitored
    • A QPCR assay that is positive for BCR-ABL1 at 6-12 months after transplant is associated with a higher riskof relapse
    • On follow-up, the patient may also have TKIs or Omacetaxine, DLI or Interferon/Peginterferon, or may been rolled in a clinical trial

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 & 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 & 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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