A small retrospective review has explored a rare but important clinical dilemma.
Women who fall pregnant after completing leukaemia treatment have better outcomes than women diagnosed while pregnant, new research has shown.
A pregnant woman being diagnosed with acute leukaemia is rare but can lead to a series of challenging clinical decisions. There are risks to the mother in delaying treatment until after they have given birth, but there are also risks to the fetus if chemotherapy is started while the mother is still pregnant.
“There is no standard approach for the treatment of acute leukaemia during pregnancy and the effects of such therapy on subsequent fertility are not fully understood,” a team of British researchers wrote in the British Journal of Haematology.
“There is, therefore, a need to gather data on pregnancy-related outcomes among women who previously received treatment for acute leukaemia to address this unmet need.”
Thirty-two patients were identified from eight NHS sites in the United Kingdom and were followed for up to four years after giving birth. Twelve women were diagnosed with acute leukaemia or high-risk myelodysplasia during pregnancy (median age at diagnosis 31 years), while 21 women fell pregnant after successfully completing chemotherapy for acute myeloid leukaemia (median age at diagnosis 26 years).
“One woman belonged to both groups, being diagnosed with AL while pregnant and then becoming pregnant again after successful treatment for AL,” the researchers said.
Of the 12 women who were diagnosed with leukaemia during pregnancy, seven were diagnosed with acute myeloid leukaemia, three with lymphoblastic leukaemia/lymphoma, and two with high-risk myelodysplasia.
Ten of these women completed their pregnancy and gave birth to a live infant, with eight women receiving a caesarean. Six deliveries occurring before they started chemotherapy and two received chemotherapy both antenatally and postnatally. Data on the timing of chemotherapy for the two remaining women were missing. One of the two remaining pregnancies resulted in an induced abortion, while the outcome of the last pregnancy was unknown.
One of the ten infants was extremely preterm (<28 weeks’ gestation), two were very preterm (28-32 weeks), and seven were moderate to late preterm (32-37 weeks), but all 10 infants were alive 28 days after delivery. The eight infants with data available had a median birthweight of 1668g.
“Our finding of low birthweights and prematurity in neonates born to patients diagnosed during pregnancy may reflect the earlier dates of delivery in this group, rather than an effect of the concurrent acute leukaemia,” wrote the researchers.
“As a result, expert opinion suggests that delivery should be delayed until at 37 weeks gestation in pregnancies complicated by acute leukaemia. Concerns in relation to the teratogenicity of chemotherapy are valid, but the risk is predominantly related to fetal exposure to such therapy in the first trimester.”
Seven of the 12 women were alive at the two-year follow-up. Of the other five women, three had died and two had an unknown survival status. Two of the three women who died had a known cause of death: infection secondary to active leukaemia in one and bronchopneumonia in the setting of acute myeloid leukaemia in the other. Five women had a recorded relapse after two years (including two of the three who died), while three did not relapse.
There were no additional deaths recorded at the four-year follow-up. Five women were still alive and four were reported to have remained in remission.
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“Evidence and expert opinion suggest that successful treatment of acute leukaemia during the second and third trimesters, with the fetus in utero, is feasible with leukaemia complete remission rates of up to 80% after standard chemotherapy,” the researchers said.
The 21 women who fell pregnant after completing chemotherapy were made up of 14 with acute myeloid leukaemia, six with B-lymphoblastic leukaemia/lymphoma, and one with high-risk myelodysplasia. There were 25 pregnancies in this group of women, leading to 23 confirmed deliveries (14 vaginal) of 25 living infants (including two sets of twins), one miscarriage, and one pregnancy of unknown outcome.
Four women experienced complications during their pregnancy: one fetus was in the breech presentation, one woman experienced postpartum haemorrhage, and two women had haemolysis with elevated liver enzymes and low platelet syndrome.
Most infants were full term (>37 weeks, n = 17), with two moderate to late preterm, one very preterm, and three extremely preterm. The median birthweight was 3257.5g (data missing for five infants). One infant had a missing survival status at 28 days after delivery, and the remaining 24 were known to be alive.
Eighteen women were alive two years after giving birth, with one death and two who had been lost to follow-up. Two women had relapsed during this time. In the women with four-year data available, 10 were alive and without relapse.
“Though extrapolation from a limited dataset is difficult, this does indicate that women successfully treated for acute leukaemia can be reassured that, if they become pregnant, their pregnancy outcomes are likely similar to those in women who have not been treated for acute leukaemia,” the researchers said.
Limitations of the study included its retrospective and descriptive design, as well as frequently incomplete data.
“Currently available practice guidance suggests that during the second and third trimester, pregnancy-associated acute leukaemia can usually be managed with deferred delivery and antenatal chemotherapy,” the researchers concluded.
“Such an approach may reduce the impact of prematurity on the affected neonate. It is possible that a shift in the treatment paradigms for acute myeloid leukaemia and acute lymphoblastic leukaemia away from intensive chemotherapy may be associated with reduced maternal and neonatal complications.”
