We have just received the following case:

"I have just diagnosed a 37 year old female tennis coach with chronic phase CML, the white cell count is only 13, she has no palpable spleen, and is generally well. She wants to conceive.

Sokal low risk – no myeloblasts, normal platelets. Otherwise well, past history of deep vein thrombosis only.

I recognize imatinib not recommended in pregnancy with reports suggesting a number of congenital malformations.
My options would be to treat to response first, cease glivec then pregnancy off treatment or pregnancy now and hope no rapid progression – IFN if necessary and caution risk venous thromboembolism/prophylaxe.

There is limited literature, but are you aware of any change in natural history of CML in pregnancy or any other suggestions?"

My main concern is that for the first 2-3 years after diagnosis of chronic phase CML there is a significant risk of progression to the acute phase if tyrosine kinase inhibitor (TKI) therapy is not commenced. The risk is at least 10-15% per year in patients who are not treated with a TKI compared to only 2-4% per year in patients treated with imatinib. The risk may be even lower for patients treated initially with a second generation TKI. If your patient chooses to defer effective therapy while they attempt to conceive this might mean 12 months or more of minimal or no treatment for her CML and consequent exposure to a substantial risk of progression to the acute phase.

I would urge her to start TKI therapy straight away, aiming to achieve AT LEAST major molecular response (MMR) but preferably complete molecular response (CMR) before stopping her TKI therapy and attempting to conceive. Given the significant risk of major fetal malformations if a baby is conceived while the mother is taking imatinib I would strongly advice this patient to maintain effective contraception until she stops TKI therapy.

Based on your description this patient probably has a low Sokal score so the transformation risk I quoted above may be a little lower in her case. However this would not change my advice. Assuming she has a low Sokal score she has a great chance of a normal life span if she starts TKI therapy soon - the stakes are very high.

Since this patient is currently 37 years old it may be very difficult for her to defer starting a family. This is a common and difficult dilemma. In the end the patient must make the decision but it is important that they know the risks of delaying or prematurely stopping TKI therapy, as well as the risks to the fetus of conceiving while on imatinib therapy.

Regards,

Tim Hughes

My only two thoughts would be that first perhaps one should start with a more powerful TKI such as nilotinib or dasatinib. Second, maybe one should aim at a CCyR initially and continue on the same TKI for for a few more months with the aim of achieving an MMR but not make that the principal target before interrupting.

John Goldman

I recently had such a case, but slightly different. A 35-year old woman (referred to me), who is in complete molecular remission on Imatinib, and who told me she would have a baby, regardless of what I could say. But if I had a suggestion, she was prepared to think about it. An important point is that she was diagnosed in accelerated phase (based on a high basophil count). So I propose her to stop Imatinib, to be put on Interferon-alpha, and to wait for 6 months. I plan to perform 2 (3 and 6 months qPCR). If she remains in CMR, I think a pregnancy could be contemplated. The question is whether I should continue IFN (which seems to be rather innocuous) or stop it when she starts giving up contraceptives.

I also think that Nilotinib 300mg BID should be the initial choice as it gives faster and higher chances of obtaining MMR and perhaps also CMR. Once that one of this goal is achieved (lower the BCR-ABL is, better it is) the lady can stop and plan to conceive. The rest as already written by Tim and John

I would like to discuss about the results of recently published data on combination of Imatinib and PegIFN ( SPIRIT, NEJM Dec 23) with the patient. Although this approach may be considered experimental at present but seems logical in this particular patient who wants to conceive after some time. Once she achieve CCyR or MMR, PegIFN may then can be continued in pregnancy..

Regards and happy new year 2011