Fig. 2 : Proposed treatment approach in patients with CML.

Allogenic bone marrow transplantation, if a suitably matched family donor is available, should be carried out in all patients during the early chronic phase.

Conventional Single-Agent Chemotherapy

• Hydroxyurea, as a single agent, is indicated for all patients for symptomatic relief and also for patients presenting with leukocytosis for rapid cytoreduction (before starting treatment with alpha-interferon with or without Ara-C). Hydroxyurea 20-30 mg/kg per day continuously or 80 mg/kg per day 2-3 times per week intermittently is the drug of choice. It is used either in intermittent schedules to maintain a WBC count between 10,000 and 50,000/mm3 or in continuous schedules to control the WBC count at a range of 2000 to 5000/mm3. Hydroxyurea does not induce cytogenetic remission.
  
  Before starting any specific antileukemic therapy, the patient should be treated for metabolic complications, hyperleukocytosis, and its complications.
  
  
• Alpha-Interferon: This treatment results in a median survival of 60-65 months with 25% of patients in durable cytogenetic remission. Alpha Interferon therapy appears to be superior to conventional therapy; as evaluated by cytogenetic response and survival, and may be preferable to allogeneic BMT in the absence of an HLA-identical sibling match.
  
  

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Alpha-Interferon: 5 x 10⁶ units/m² IM or SC per day for 9-15 months

This dose is reduced by 50% if any of the following indications of toxicity are observed:

• Development of neurologic symptoms of Parkinsonism, memory change, reduced attention span.
  
  
• Increase in liver enzymes to more than 5 times the normal values
  
  
• Increase in serum creatinine to 2.5 mg/dl or more
  
  
• Decline in performance status to 80% or less of the Karnofsky scale
  
  

Discontinue Alpha -Interferon when the ANC in less than 750/mm³ or the platelet count is less than 40,000/mm³

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Early flu-like side effects (fever, chills, anorexia, postnasal drip) are minimized by starting a-interferon at 50% of dose for the first week of treatment)

• Alpha Interferon with hydroxyurea: This regimen provides rapid disease control, decreases the incidence of side effects attributable to leukocytosis (fever, chills, musculoskeletal syndrome), and provides longer duration of disease control. However, it does not improve the cytogenetic response rates.
  
  
• Alpha Interferon with low dose Ara-C : (Table 4) : Similar results as with alpha-interferon with hydroxyurea can be obtained with this regimen.
  
  

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Alpha -Interferon: 5 x 10⁶units/m² SC daily

Ara-C:   15 mg/m² daily by continuous infusion or in two divided doses SC for 2 weeks every 2 weeks until hematologic remission

15 mg/m² daily by continuous infusion or in two divided doses SC for 1 week during hematologic remission.

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Management of Blastic Phase

Treatment of myeloid blastic phase : Treatment with standard anti-AML chemotherapy is disappointing.

Treatment of lymphoid blastic phase : This can be treated with vincristine and prednisone. Approximately 50-60% of patients attain remission and may revert to chronic phase.