Can a patient with Chronic Myeloid Leukemia (CML) on Tyrosine Kinase Inhibitors (TKIs) have children?

Family Planning for CML Patients on TKI Therapy

For CML patients on TKI therapy, pregnancy is possible but requires careful planning and management, with different considerations for men and women due to the teratogenic effects of TKIs in women but not men.

For Male CML Patients on TKIs

TKI therapy does not significantly affect male fertility or increase risks to offspring:

• Men can safely father children while continuing TKI therapy without increased risk of congenital abnormalities in their offspring 1
• TKIs may transiently affect some male hormones but do not appear to have deleterious effects on male fertility 1
• Studies show that 91% of women who conceived with dasatinib-treated men delivered normal infants 1
• Changes in sperm quality and morphology can be present at CML diagnosis but remain unchanged after imatinib treatment 1

For Female CML Patients on TKIs

TKIs are teratogenic and contraindicated during pregnancy, particularly in the first trimester:

• Women must discontinue TKI therapy before attempting conception due to significant risks of miscarriage and fetal abnormalities 1
• Data from case reports show concerning outcomes with TKI exposure during pregnancy:
  • 50% normal pregnancies and 10% fetal abnormalities with imatinib exposure 1
  • 33% normal deliveries, 56% abortions (spontaneous or elective), and 11% abnormal pregnancies with dasatinib exposure 1
• All TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) are considered unsafe during pregnancy 1

Recommended Approach for Women Planning Pregnancy

Pre-conception planning:

1. Achieve and maintain deep molecular response (DMR) before attempting pregnancy 1
2. Consult with CML specialist and high-risk obstetrician before discontinuing TKI 1
3. Discontinue TKI therapy with adequate washout period before conception 1
4. Consider fertility preservation options before starting TKI therapy for newly diagnosed patients 1

Monitoring during pregnancy:

1. Monthly monitoring with qPCR is recommended 1
2. Initiate treatment if BCR-ABL1 IS increases to >1.0% 1
3. If treatment is necessary during pregnancy:
   • Interferon alpha is preferred (safe throughout gestation) 1
   • Leukapheresis can be used for rising white blood cell counts 1
   • Low-dose aspirin or low-molecular-weight heparin for thrombocytosis 1
   • Avoid hydroxyurea especially in first trimester 1

Post-delivery management:

1. Resume TKI therapy after delivery 1
2. Breastfeeding is contraindicated while on TKI therapy as TKIs pass into breast milk 1
3. Brief TKI-free period (2-5 days) may be acceptable to provide colostrum 1
4. Close molecular monitoring for women who extend treatment-free period for breastfeeding 1
5. If MMR is lost, breastfeeding should be terminated and TKI restarted 1

Risk Stratification for Treatment Discontinuation

Women who meet criteria for TKI discontinuation (treatment-free remission) have better outcomes:

Minimal criteria for TKI discontinuation (stop allowed) 1:

• First-line therapy or second-line if intolerance was the only reason for changing TKI
• Typical BCR-ABL1 transcripts
• TKI therapy >5 years (>4 years for 2nd generation TKIs)
• Duration of DMR (MR4 or better) >2 years
• No prior treatment failure

Optimal criteria (stop recommended) 1:

• TKI therapy >5 years
• Duration of DMR >3 years if MR4
• Duration of DMR >2 years if MR4.5

Important Considerations and Caveats

• Disease relapse risk: Women who discontinue TKI without achieving DMR have approximately 60% chance of molecular relapse 1
• Response recovery: Most patients who lose response during pregnancy regain it after resuming TKI therapy post-delivery 2
• Monitoring frequency: More intensive monitoring is required during pregnancy - monthly for the first 6 months after TKI discontinuation 1
• Emergency planning: Have a clear plan for managing disease progression during pregnancy if it occurs 1
• Referral recommendation: Patients should be referred to a CML specialty center for management 1

By following these guidelines, CML patients can make informed decisions about family planning while managing their disease effectively.