Treatment of haematological malignancies during pregnancy can result in good maternal and foetal outcomes and doesn’t equate to an immediate termination or premature delivery for most patients, delegates at Blood 2023 have heard.
Dr Giselle Kidson-Gerber, a haematologist at Prince of Wales Hospital and the Royal Hospital for Women, Sydney, said there needed to be standardised guidelines and pathways, as well as inclusion of pregnant women in clinical trials.
Presenting in Melbourne on Tuesday, Dr Kidson-Gerber, who subspecialises in obstetric haematology, said cancer incidence in pregnancy was estimated to be one in every 1000 pregnancies, including diagnoses in the following 12 months.
She said that incidence was increasing, which might be partly due to increasing maternal age, with haematological malignancies ranking second in incidence after breast cancer.
“Everyone’s terrified about the baby and wants to get rid of it but we actually want to make sure this woman has the best treatment and has an educated understanding of the risks,” said Dr Kidson-Gerber, who co-founded the Haematology in Obstetrics and Women’s Health (HOW) Collaborative.
“We try to avoid termination in all situations, but often during the first trimester of acute leukaemia that really is the best option for the mother.”
She said a quick referral to specialised care including the involvement of a multidisciplinary team with experience in caring for the population was critical.
Dr Kidson-Gerber said there could be delays in diagnosis, either due to nonspecific symptoms such as fatigue or dyspnea being attributed to the pregnancy or patient or clinician reluctance to investigate further in pregnancy with invasive tests.
When it came to imaging, Dr Kidson-Gerber said the goal was to get the most amount of information with the least amount of risk, with the anatomical location of the mass, gestational age and expected radiation dose all taken into account.
Foetal radiation doses and the effects
In weeks 2-4 of pregnancy there was an all or nothing approach (miscarriage or no effect).
From weeks 4-10, Dr Kidson-Gerber said if the exposure to the foetus was more than 200 mGy, there was concerns around increased risk of congenital malformations, which could involve all organs, and intrauterine growth restriction.
From weeks 10-17, Dr Kidson-Gerber said a threshold of more than 200 mGy was associated with microcephaly and potentially intellectual impairment.
After 18 weeks, the threshold was about 250 mGy.
Dr Kidson-Gerber stressed it was okay to undergo imaging for a good reason and there were methods to reduce exposure such as abdominal shielding for CT scans.
Management of haematological malignancy in pregnancy
Data from the International Network on Cancer, Infertility and Pregnancy showed there were more live births despite increasing use of chemotherapy in pregnancy.
Dr Kidson-Gerber referred to a study of 134 women, of whom 54% received antenatal chemotherapy. The researchers looked at the obstetric outcomes, comparing babies of mothers who had lymphoma with no chemotherapy to the mothers who had lymphoma and also received chemotherapy during pregnancy.
There was no difference in small for gestational age or NICU admissions. However, there was lower birth weight, increased preterm contractions and ruptured membranes associated with the chemotherapy group.
Notably, the women’s five-year progression-free survival and overall survival was equivalent to age matched controls who were not pregnant during their diagnosis.
In a study of 80 women, 68% of women received chemotherapy that was CHOP-like. As for obstetric complications, 39% had small-for-gestational-age babies, 52% had preterm delivery of which 46% were planned, and 25% who received antenatal chemotherapy had spontaneous preterm labour, Dr Kidson-Gerber said.
The three year progression-free survival and overall survival appeared comparable for both limited and advanced stage Non-Hodgkin lymphoma, she added.
Acute leukaemia (AML or ALL)
Dr Kidson-Gerber said data were lacking but the available evidence showed delayed chemotherapy or reduced intensity regimen resulted in inferior outcomes.
She presented a single centre study in China involving 21 women. Four died before chemotherapy, six had terminations and one had a spontaneous miscarriage.
Of the nine babies born between 2010-2019, all were low birth weight, including five born at term and five who didn’t receive any chemotherapy. None of the four babies exposed to chemotherapy had malformations or developmental concerns.
“The complete remission rate was better in those who received immediate chemotherapy, as opposed to those for whom it was delayed, and the outcomes are abysmal. At 24 months, only three [women] were alive,” Dr Kidson-Gerber said.
Impact of chemotherapy on the foetus
Dr Kidson-Gerber said chemotherapy in the first trimester carried the risk of foetal malformation and miscarriage, whereas in the second and third trimesters risks included preterm birth, stillbirth (very small increase) and foetal myelosuppression.
“We try to deliver about two weeks after last chemotherapy to avoid neonatal immunocompromise and allow for haematopoietic recovery,” she said.
Data showed 21% of babies exposed to chemotherapy in the first trimester had major congenital malformations, whereas the rate was 3% for babies exposed to chemotherapy after 12 weeks, consistent with the general population.
There also appeared to be no long-term major developmental consequences of in utero exposure to chemotherapy in the second and third trimesters, she said.
In fact, one study showed preterm delivery was the main risk factor for developmental problems up to age three – not antenatal chemotherapy exposure.
“There’s been a shift in our management. We want to avoid delivering babies who are at risk of long-term damage from prematurity, so we administer chemotherapy so that the baby will be delivered later rather than earlier with greater risk.”
Dosing was based on current maternal weight with close foetal monitoring.
Dr Kidson-Gerber also stressed the need for more data to inform treatment approaches.
“Most trials exclude pregnant and lactating women and contraception is mandatory. We know that clinical trials have an important role in improving cancer care and it might provide additional access to medications,” she told delegates.
“We need to work out how we can include these women in our trails.
“In the future, we need guidelines and pathways (including standardisation of investigation and standardisation of management) and long-term follow up.
“It is not a terrible situation, we can give them hope and we can treat them well.”