I agree with Franck, although the dose needs to be worked out. I would start her on Pegasys at 180mcg weekly and titrate the dose interval based on counts. If Pegasys is not available then use regualar IFN again titrating the dose and/or interval to keep the counts appropriate. Monitor the molecular level over the next 6-9 months and then if stable, she should try to get pregnant. There is some suggestion that eggs harvested while women are on imatinib may not be the best for IVF and early in vitro embryo death has been noted. Interferon is quite safe in pregnancy and I have had 2-3 patients on interferon undergone fertility therapy that resulted in successful pregnancy. This can include stimulation if necessary while on interferon. If the molecular response is lost during the 6-month observation period, then resume the TKI after harvesting eggs. I daresay the likelihood of this woman being able to stop TKI at a later date will be quite small if she could not stop and switch to interferon successfully at this stage.

In this case with this level of response, I usually use Peg-IFN alfa 2a (Pegasys Roche) 90 microg/week subcutaneously or IFn-alfa 2a (Roferon Roche) 3 millions units 3 times a week. Usually transcript raise to 1% and stabilize thereafter around this value. I ussually carry out interferon until the end of breastfeeding (if any) as TKi are excreted in maternal milk.
Franck

Hi Tara. I agree with Tim, and I would not start imatinib until the loss of MMR. Around 25-30% of these initial increases in the amount of BCR-ABL are only transient and then They are followed by a return to MR4 or lower. In the meanwhile, she can continue to search to become pregnant and then, if she will lose MMR not pregnant she can restart imatinib (or nilotinib) whereas if she will lose MMR and then CCyR being pregnant she can start IFN.

The suggestion by Tim to storage of her fertilized eggs and use them after years(?) of 2ed gen TKI treatment is an excellent suggestion. It you'll be helpful to repeat the PCR ASAP to consolidate the rate of reappearance of CML. Concerning the IFN-a issue, I don't know if there is a consensus in the dose in CML pts' based on data in the IFN era. I have used 3Million U/day sc in a pregnancy with CML mainly due to lack of toxicity to the fetus ,with the hope of delaying CML reappearance.

Panos

Your patient has only had 4 years of TKI therapy so it is not surprising that she has not achieved TFR even though she has been in CMR for almost 3 years. Given the probable tempo of her rise in BCR-ABL she will rapidly lose cytogenetic and possibly also haematological response over the next few months. This doesn’t mean she has to restart imatinib – she may find the risk of 9-12 months of uncontrolled or poorly controlled CML over the period of her pregnancy quite acceptable. It is hard to put a figure on the risk of transformation over this period but it is probably less than 10%. If she does find this risk unacceptable then she can restart imatinib and wait another 3 or so years then try again. If she wants to forge ahead with a pregnancy attempt now despite the risk then you could consider giving her some interferon (low dose – maybe 1 million 3 times weekly initially) but I wouldn’t start until the second trimester.

Another possibility would be to proceed with the harvest and storage of fertilised eggs at this stage (now that she has progressed this far) allowing her to move straight into a pregnancy in a few years when TFR is more likely. This might allay some of her concerns about the delay involved in actually getting pregnant given her low ovarian reserves.

Very little of what I have suggested above is evidence-based. It might be interesting to get some wider discussion on this case.

Further update - This young lady, CML diagnosed in in June 2011. Has been in a complete molecular remission (on 600mg Glivec) since Aug 2012.

She wants a baby – fertility tests done whilst on glivec show low ovarian reserve.

Anyway I ceased the Glivec 2 months ago, the BCR-ABL is now detectable at 0.011 – she is not pregnant yet but is about commence Clomid to induce ovulation.

Any suggestions? Should I commence interferon (if so what is your usual starting dose)?