Treatment

Once a diagnosis of chronic myeloid leukaemia is made a frank discussion of the implications is a priority.

• patient is informed that the disease reduces life expectancy but that several years of relatively normal life can be expected. In the older patient (40-50+) emphasis is placed on palliative treatment
• women who are diagnosed with CML during pregnancy should be advised that continuing to term will not affect the outcome of the pregnancy or the leukaemia.
• cryopreservation of the patient's buffy coat should be performed if autologous stem cell transplantation may be considered at a latter stage.
• young males should be offered cryopreservation of semen as infertility is a risk.

Specific palliative drug therapy includes:

• imatinib (see notes)
• recombinant alpha interferon
• hydroxyurea
• busulphan
• newer tyrosine kinase inhibitors (TKI’s) - nilotinib, dasatinib (1)

Transplant therapies

• autologous stem cell transplantation (SCT)
  • may prolong survival but does not reduce mortality
  • there is no clear evidence on the benefits of autologous SCT as the initial treatment of CML (2)
• allogeneic bone marrow transplantation
  • allogeneic stem cell transplantation (SCT) is no longer recommended as the first-line therapy in CML,
  • it is the recommended method after imatinib failure (except in high disease risk and very low transplantation risk, patient’s preference, or economic reasons) (1)
  • 30% of patients will have a HLA-matched sibling who can act as a donor
  • mortality and morbidity from this procedure may vary between 10% to 70% (1)

Leukopheresis is used in exceptional situations to reduce the peripheral white cell count.

The following are the recommendations from the European LeukaemiaNet for the management of CML:

• in chronic phase
  • 1st line
    • in all patients - Imatinib 400mg daily
  • 2nd line (after imatinib)
    • higher imatinib dose
    • dasatinib or nilotinib
    • allogeneic stem cell transplantation
• in accelerated and blastic phase
  • allogeneic stem cell transplantation, preceded by imatinib, dasatinib or nilotinib (3)

Notes (2):

• imatinib is recommended as first-line treatment for people with Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) in the chronic phase
• imatinib is recommended as an option for the treatment of people with Philadelphia-chromosome-positive CML who initially present in the accelerated phase or with blast crisis. Additionally, imatinib is recommended as an option for people who present in the chronic phase and then progress to the accelerated phase or blast crisis if they have not received imatinib previously
• the NICE guideline (2) has defined imatinib as the first-line palliative treatment for CML whereas previously alpha interferon was used in this role
  • interferon-alpha (IFN) was considered the gold standard for drug therapy of CML, as it yielded complete cytogenetic response (CCR) in 10-25% of patients with significant survival prolongation, particularly in low risk patients usually obtaining a higher response rate
    • however, even in best responding patients, the disease still remained detectable at a molecular level, and the majority of patients eventually relapsed
    • imatinib mesylate, a selective inhibitor of the BCR/ABL TK, has revolutionized the disease management, as it induces CCR in 50-90% of chronic phase (CP) CML patients, including those resistant or refractory to IFN alpha (3)
    • there is study evidence that indicates that patients induced into CCR by IFN treatment represent a subset with very favourable prognosis, which can significantly improve molecular response with imatinib (3)
    • high-dose imatinib is not recommended for the treatment of chronic, accelerated or blast-crisis phase Philadelphia-chromosome-positive CML that is resistant to standard-dose imatinib (7)
• NICE have given guidance regarding the use of Azacitidine in CML (6)
• NICE (7) have stated that nilotinib is recommended for the treatment of chronic or accelerated phase Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) in adults:
  • whose CML is resistant to treatment with standard-dose imatinib or
  • who have imatinib intolerance and if the manufacturer makes nilotinib available with the discount agreed as part of the patient access scheme

Reference:

• (1) Hehlmann R et al. Chronic myeloid leukaemia. Lancet. 2007;370(9584):342-50.
• (2) CML Autograft Trials Collaboration. Autologous stem cell transplantation in chronic myeloid leukaemia: a meta-analysis of six randomized trials. Cancer Treat Rev. 2007;33(1):39-47.
• (3) European LeuemiaNet (ELN). Recommendations from the European LeukemiaNet for the Management of chronic myeloid leukemia (CML)
• (4) NICE (October 2003).Guidance on the use of imatinib for chronic myeloid leukaemia
• (5) Alimena G et al. Imatinib mesylate therapy in chronic myeloid leukemia patients in stable complete cytogenic response after interferon-alpha results in a very high complete molecular response rate. Leuk Res. 2008 Feb;32(2):255-61
• (6) NICE (March 2011). Azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia
• (7) NICE (January 2012). Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia (CML)