I have been treating a 20 year old female patient since April 2014 when I met her during her first pregnancy - G1P0 - 8/40 weeks.
She was diagnosed with CML chronic phase in December 2011. Conventional Philadelphia chr and BCR-ABL (P210 fusion gene).
Initial therapy imatinib 600mg daily - complete molecular response (bcr-abl >4 log reduction), but poor compliance.
First pregnancy ¬ introduced imatinib during the last 6 weeks and achieved stable haematological response, no drop in transcripts. Modest progression only during pregnancy
8/40: neut 11, plt 600, bcr-abl 4.2%, no spleen
28/40: neut 50, plt 900, bcr-abl 130s - recommenced imatinib
36/40: neut 10, plt 507 - delivered 38 weeks – healthy baby, who is thriving.

Patient is intolerant with grade 2/3 nausea/fatigue and so really just remained non-compliant. Changed to dasatinib (Feb 2015): completed near 3 months with excellent response, complete haematological and molecular (at least 2.0 log reduction after one month therapy)

Current Status: Pregnant 9/40 weeks
1. (self) Ceased dasatinib May 2015 ¬when she and her partner decided to try for a second pregnancy
2. Routine review in July 2015 when she told me she was trying for a baby; already signs of loss of response
3. She agreed to recommence in September, when her WCC/plt started to rise. Took approx. 1 week of dasatinib and realised she was pregnant and so ceased therapy without notification or advice to do so.

She is very keen to continue with pregnancy BUT
Wcc 90/plt 800s.
No thrombohaemorrhagic events and clinically well
Spleen not enlarged.

Would appreciate any opinions on the options:
a. Leucopharesis? - Is a possibility. Would consider if further advanced in pregnancy but huge resource for hospital and for her...so not currently near top of the list.

b. IFN? - Takes longer and not convinced (at all) she will remain complaint for 30weeks and she needs to learn to self-inject...also hopefully not near the top of the list.

c. Hydroxyurea pulsed intermittently to control WCC/plt
What are people’s opinions on pulsed verses continuous (cumulative) hydrea, to control
myeloproliferation (specifically leucostasis and plt)?

d. dasatinib - possibly introducing this late - post 3rd trimester, as I know she is sensitive.

My issue is deliverability and commitment of whatever therapy/management I choose.

Thanks in advance for your thoughts.

Kate

It is unfortunate that she didn’t wait until she had achieved a deeper and more stable molecular response before attempting to have a second child, she would have probably been much easier to manage in pregnancy then. The challenge now is to keep her disease under control and her fetus safe through this pregnancy. I think the use of imatinib in the third trimester is becoming a more common practice and there is no published or anecdotal evidence that there is a high risk of toxicity for the fetus in this context.
Very concerned about using nilotinib or dasatinib in any phase of pregnancy though. The case of fetal cytopenia with dasatinib really concerns me. I would be inclined to restart imatinib in the third trimester rather than dasatinib – just enough to regain haematological control (I presume she would still be sensitive based on her prior response and assume that she doesn¹t have any KD mutations). For the next few months I would probably avoid anything except leukapheresis for the first trimester and then try interferon or pulses of hydroxyurea in the second trimester, if you have to use anything.

About the only thing that can safely control counts is probably aggressive leukopheresis. This may be necessary several times per week. Although interferon is safe during pregnancy, I doubt the effectiveness in this case partly because of my concerns about compliance, especially due to the fatigue due to both interferon and pregnancy and past history, and secondly because of the maturity of the disease. Interferon as a late addition to her therapy often is minimally effective. I would be most concerned about disease progression during the pregnancy. I agree with Tim about hydroxyurea use if it becomes necessary. I also am very uncomfortable with any TKI during pregnancy, although there may be less risk during the third trimester. Personally, I would avoid them completely. Once she has delivered, I would try to get her back on definitive therapy immediately, try to get her to pass on breast feeding as the drugs also get into breast milk. I think she needs to have a good chat about family planning given her risk of disease progression and the chance that she will never see her kids grow up if her CML goes acute. My approach here is defnitely hard line, but there needs to be a reality check here.