Risks and challenges of CML management during pregnancy: Looking for a balanced decision

Abstract

On the other hand, in many situations, pregnant patients with CML may be observed without any therapy for the whole pregnancy period. New data about the kinetics of the leukemic clone during pregnancy indicate the possibility of slowly increasing BCR-ABL levels after TKI cessation. 12 Moreover, patients with non-sustained DMR and even with a major molecular response (MMR or BCR-ABL ≤0.1% IS) who lose their response when TKI is interrupted during pregnancy, restore their initial response after re-initiation of TKIs. 13 However, the probability of restoring MMR was 78% two years after resuming TKI in patients with an initial MMR. Again, these findings need further confirmation and a longer follow-up with careful | 379 LETTER TO THE EDITOR molecular monitoring in order to find the optimal degree of remission to be observed without therapy during pregnancy.The authors suggest the possibility of imatinib or nilotinib use after the 16th week of pregnancy and note that an unplanned pregnancy needs to be managed relative to TKI exposure and the CML disease state. In fact, we have been using this approach with just the same timepoint for treatment initiation in our center for several years. The results of the LET (leukemia and term-related) scheme were presented at the 2018 annual meeting of the European Hematology Association. Briefly, 49 CML pregnancy cases were managed in accordance with the level of BCR-ABL and pregnancy stage. 14 Any TKIs were immediately discontinued after pregnancy confirmation, and none of them were used during organogenesis before the 15th week of pregnancy. Imatinib or nilotinib was used after the 15th week of pregnancy for the benefit of patients with no complete hematological response (CHR) or MR2 loss (BCR-ABL >1%); 26 patients were given imatinib and four patients received nilotinib. No other TKIs were administered at any stage of pregnancy.Observation without IFN was used if at least MR2 remained (BCR-ABL <1%). If no CHR was observed before the 15th week, an IFN could be administered. The newborns were healthy, and no congenital abnormalities occurred. A single case of hypospadias was observed with no association of TKI use as the mother received IFN for the whole pregnancy.The article by Abruzzese et al gives directions for the development of recommendations in patients with CML during pregnancy.We are encouraged by the current vision of international experts from different countries, which accords well with our considerations and experience, and we hope that our experience may contribute to a consensus in the practical management of CML patients during pregnancy.

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

“…Acetyl salicylic acid and/or low molecular weight heparin are indicated for thrombocytosis. Leucapheresis and/or IFNα are safe throughout gestation [122,130]. Close collaboration with obstetricians and regular fetal ultrasound examinations are recommended.…”

Pregnancy Outcomes in Patients Treated with Bosutinib

“…Reports have recommended a collaborative approach between the patient and the hematology and obstetric teams regarding the management of pregnancy during TKI treatment for CML. Ideally, female patients with CML who wish to become pregnant should do so when in sustained molecular response and should stop therapy upon conception [ 7 , 9 , 10 , 18 , 19 ]. The effects of bosutinib on pregnancy experienced in the current study were largely similar to those reported for other TKIs, and female patients with CML should not be exposed to TKIs during pregnancy [ 5–11 , 20–23 ].…”

A krónikus myeloid leukaemia tirozin-kináz-gátló kezelésének mellékhatásai és azok gyakorlati ellátása

“…Noha az imatinibet biztonságosan alkalmazták a második és a harmadik trimeszterben, a rendelkezésre álló, igen kevés tapasztalat alapján nem javasolt a rutinalkalmazás. A TKI az anyatejbe kis koncentrációban kiválasztódik, a szoptatás ideje alatt nem javasolt a használatuk [41].…”