chronic%20myeloid%20leukemia
CHRONIC MYELOID LEUKEMIA

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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With the dramatic evolution of sequencing technology and emergence of effective targeted therapies, using a comprehensive molecular approach to guide treatment decisions is becoming more accessible and applicable in the clinic. At the recent Foundation Medicine meeting in Hong Kong, Dr Alexander Drilon, clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSKCC), New York, US, discussed the current landscape and potential benefits of comprehensive molecular profiling in non-small cell lung cancer (NSCLC).