Chronic Myeloid Leukemia Follow Up

Monitoring

Treatment Response Assessment  

Complete Hematologic Response

• Normalization of the peripheral blood counts with <10 × 10⁹/L of leukocytes
• <450 × 10⁹/L platelet count
• <5% basophils
• Immature granulocytes (eg myelocytes, promyelocytes, blasts in peripheral blood) absent
• Spleen is non-palpable and no signs and symptoms of the disease

Cytogenetic Response

• No Ph-positive metaphases: CCyR
• 0-35% Ph-positive metaphases: Major cytogenetic response (MCyR)
• 1-35% Ph-positive metaphases: PCyR
• >35-65% Ph-positive metaphases: Minor cytogenetic response
• 36-95% Ph-positive metaphases: Minimal cytogenetic response
• >65% Ph-positive metaphases: Cytogenetic response absent

Molecular Response

• Early molecular response (EMR): BCR::ABL1 transcripts ≤10% by qPCR (IS) at 3 and 6 months
• MMR: BCR::ABL1 transcripts ≤0.1% by qPCR (IS) or a reduction of ≥3 log in the BCR::ABL1 mRNA, if qPCR (IS) is unavailable
• DMR: BCR::ABL1 values of ≤0.01% IS and is described as various BCR::ABL1 cutoff values (ie MR4.0 ≤0.01% IS, MR4.5 ≤0.0032% IS)

Relapse

• Any signs of loss of hematologic response or CCyR (BCR::ABL1 ≤1%) or its molecular response correlate (MR2.0: BCR::ABL1 [IS] ≤1%) (increase in BCR::ABL1 transcripts to >1%)
• 1-log increase in the BCR::ABL1 transcripts level with loss of MMR

Monitoring Response to TKI Therapy  

Hematologic Tests  

CBC is recommended ever 1 to 2 weeks within the first 1 to 2 months of treatment or until blood counts stabilize and thereafter as indicated based on the persistence of cytopenias.  

Bone Marrow Cytogenetics  

Bone marrow cytogenetics is used to establish the phase of CML and performed at diagnosis. It may be used after the initiation of a TKI therapy at 3 and 6 months, and if qPCR (IS) is not available. It may also be done if there is a failure to reach response milestones, signs of loss of hematologic response, or signs of CCyR or its molecular correlate (increase in BCR::ABL1 transcript levels to >1%).  

qPCR  

qPCR is the preferred method for monitoring response to TKI therapy. It is performed at diagnosis. It is recommended to be performed every 3 months after the initiation of therapy, including in patients who have met response milestones. It may be repeated every 3 months for 2 years and every 3 to 6 months thereafter, if the CCyR has been achieved. It should be repeated in 1 to 3 months if the BCR::ABL1 transcript levels with MMR have increased by 1-log.  

BCR::ABL Kinase Domain Mutation Analysis  

Recommendations for CP:

• Failure to reach response milestones
• There are signs of loss of hematologic response or CCyR or its molecular response correlate (increase in BCR::ABL1 transcripts >1%)
• There is loss of MMR and the BCR::ABL1 transcript levels have increased by 1-log
• Consider myeloid mutation panel to identify BCR::ABL1-independent resistance mutations in patients with no BCR::ABL1 kinase domain mutation

Recommendations for AP or BP: To monitor if the disease has progressed to AP or BP.  

Follow-up  

Factors affecting the patient’s compliance include the length of time from diagnosis to treatment and Imatinib treatment, age, dose of TKI, living along, and male sex. 

Three Months Follow-up Therapy  

For patients with BCR::ABL1 transcripts ≤10% by qPCR (IS), the patient is advised to continue the same TKI with the same dose, and response is monitored with qPCR; adverse effects are also monitored.  

For patients with BCR::ABL1 transcripts ≥10% by qPCR (IS):

• Evaluate the compliance of the patient and report for drug interactions
• Advise the patient to have mutational analysis
• Bone marrow cytogenetic analysis to assess MCyR at 3 months and CCyR at 12 months should be considered
• Advise the patient to enroll in a clinical trial
• Change therapy to other TKIs
• May increase the dose of Imatinib to 800 mg
• May continue the same TKI other than Imatinib for another 3 months if with ≥50% reduction from baseline or >10% cutoff
• Evaluate the patient for allo-HCT

Six Months Follow-up Therapy  

For patients with BCR::ABL1 transcripts <10% by qPCR (IS), the patient is advised to continue the same TKI, and response is monitored with qPCR; adverse effects are also monitored.  

For patients with BCR::ABL1 transcripts >10% by qPCR (IS):

• Evaluate the compliance of the patient and report for drug interactions
• Advise the patient to have mutational analysis
• Advise the patient to enroll in a clinical trial
• Change therapy to other TKIs
• Evaluate the patient for allo-HCT\

Twelve Months Follow-up Therapy  

For patients with BCR::ABL1 transcripts ≤0.1% by qPCR (IS), the patient is advised to continue the same TKI, and response is monitored with qPCR; adverse effects are also monitored. One may also consider a trial of treatment-free remission.  

For patients with BCR::ABL1 transcripts ≤1% by qPCR (IS):

• Advise to continue taking the same TKI if treatment goal is optimal
  • Optimal treatment goal focused on long term survival: >0.1-1%
  • Optimal treatment goal focused on treatment-free survival: ≤0.1%
• If the optimal treatment goal is not achieved, shared decision-making with the patient on switching of treatment (Imatinib to a second generation TKI or allosteric TKI) and enrollment in a clinical trial should be considered

For patients with BCR::ABL1 transcripts ≤10% but us <1 by qPCR (IS):

• Evaluate compliance of the patient and report for drug interactions
• Consider the patient for mutational analysis
• Bone marrow cytogenetic analysis to assess MCyR at 3 months and CCyR at 12 months should be considered
• Change therapy to other TKIs
• May continue with the same TKI if other than Imatinib or increase the dose of Imatinib to 800 mg
• Evaluate for allo-HCT

For patients with BCR::ABL1 transcripts >10% by qPCR (IS):

• Evaluate compliance of the patient and report for drug interactions
• Consider the patient for mutational analysis
• May change to an alternative TKI and evaluate the patient for allo-HCT or enroll in a clinical trial

Chronic Myeloid Leukemia_Follow Up