MEDICAL MANAGEMENT

The goals of treatment of chronic myeloid leukemia (CML) are threefold and have changed

markedly in the past 10 years. They are as follows:

1. Hematologic remission (normal complete blood cell count [CBC] and physical

examination (i.e., no organomegaly)

2. Cytogenetic remission (normal chromosome returns with 0% Philadelphia chromosome

—positive (Ph+) cells)

3. Molecular remission (negative polymerase chain reaction [PCR] result for the

mutational BCR/ABL mRNA), which represents an attempt for cure and prolongation of

patient survival

CML usually has three clinical phases: an initial chronic period in which the disease process

is well controlled; a transitional and unpredictable path (accelerated phase); and finally, a more

violent course (blast crisis), which is usually lethal. Supportive treatment with red blood cell or

platelet transfusions can be used to alleviate symptoms and improve quality of life in all three

phases.

The length of the chronic process varies depending on the maintenance treatment used:

with hydroxyurea (Hydrea) or busulfan therapy, it typically lasts 2-3 years, but it can last up to

9.5 years in patients who respond well to interferon-alfa therapy. Furthermore, the introduction

of tyrosine kinase inhibitor (TKI) therapy has increased the length of hematologic and

cytogenetic remissions substantially. The median survival for most chronic-phase CML patients

treated with TKIs is expected to approach average life expectancy.

 90 percent of CML patients in Western countries are diagnosed in the chronic stage.

Medication is generally used to keep the white blood cell (WBC) count of these patients under

control (hematologic remission). During this process, the main aim of treatment is to manage

symptoms and complications caused by anemia, thrombocytopenia, leukocytosis, and

splenomegaly. In all stages of CML, the first-generation TKI imatinib mesylate (Gleevec), a

specific small-molecule inhibitor of BCR/ABL, is the treatment of choice.

Nilotinib (Tasigna), dasatinib (Sprycel), and bosutinib (Bosulif) are second-generation

TKIs that have been approved as first-line treatment for CML in the chronic process. Despite the

fact that all of these agents produce a higher rate of deep molecular response and provide better

early disease control than imatinib, the advantages and risks of these newer agents, as well as

their long-term safety profiles, have yet to be determined.

The high cost of imatinib (approximately $100,000 per year) is a major "adverse effect,"

particularly given the long duration of treatment. While a generic version is available, its

effectiveness as a first-line treatment for CML has been called into question. The European Stop

TKI Research (EURO-SKI), on the other hand, discovered that stopping TKI therapy is possible,

with around half of patients remaining relapse-free after two years of follow-up. The optimum

period of TKI therapy until discontinuation in EURO-SKI was 5.8 years or longer. Treatment

discontinuation is increasingly being recommended in carefully chosen patients, according to

guidelines.

Some CML patients go through a transitional or accelerated period that can last many

months. Patients diagnosed in this stage have a 1-1.5-year survival rate. This stage is defined by

low blood count regulation with myelosuppressive drugs, as well as the presence of peripheral
blast cells (215%), promyelocytes (230%), basophils (220%), and platelet counts less than

100,000 cells/pL that are unrelated to therapy.