ACUTE MYELOID LEUKEMIA IN PREGNANCY: DIFFICULT JOURNEY FROM DIAGNOSIS TO DELIVERY AND TREATMENT

The Incidence of Acute Myeloid Leukemia is 1 in 75,000 to 100,000 pregnancies with maximum 40% presenting in third trimester and 23% and 37% in first and second trimester respectively. In a population based study by Nolan et al [1], out of total acute leukaemia cases, two thirds are myeloblastic and one third lymphoblastic leukemia.

The rarity of disease during pregnancy, might also be due to very low reporting in view of confusing diagnosis. The symptoms of AML can easily be confused with symptoms of anaemia like malaise, easy fatigueability, low grade fever. Thrombocytopenia and anaemia are relatively common findings in pregnancy. Although, Neutropenia is rare and merits further investigation or close monitoring. But in the developing country like India, it is majorly missed. Thus, whenever there is presence of circulating blasts in a blood film, it suggests a diagnosis of haematological malignancy and is an indication for bone marrow biopsy. The other differential diagnosis that should be kept in mind are Thrombotic microangiopathy, HELLP syndrome and Cytopenias of deficiency or immune origin [2].

The tests to be done before bone marrow aspiration are Full blood count, blood film examination, Vitamin B12, folate and ferritin measurement, Coagulation screen, Renal and liver function tests. All these were done for our patient and further bone marrow aspiration was suggested with studies directed at Immunophenotypic, cytogenetic and molecular analysis for accurate subtyping and understanding of prognostic features.

Once diagnosed, a Multidisciplinary approach comprising of hematologists, obstetricians, anesthetists and neonatologists is the key to appropriate management. Consideration should be given to health of both mother and baby. The woman should be fully informed about the diagnosis, treatment of the disease and possible complications during pregnancy , clearly implying that any treatment delays might result in compromised maternal outcome without improving the outcome for the fetus [3].

The risks of Leukemia, disease per se, to pregnancy is miscarriage, foetal growth restriction, perinatal mortality, premature labour and Intrauterine fetal death [4].

Due to the high risk of the disease, there are different recommendations for management of AML in pregnancy in the three trimesters owing to the urgent need of chemotherapeutic agents and the adverse effects of the drugs involved .

If it is diagnosed in the first trimester, the patient should be counselled for elective abortion, medical/surgical and starting of chemotherapy. Between 13- 24 weeks, the Induction chemotherapy should be started while pregnancy is continued [5]. Preterm termination of pregnancy is indicated after fetal viability. Similar conclusions were derived by Nicola et al and Farhadfar in a single centre study of 5 and 23 case of AML diagnosed during pregnancy respectively [6,7].

Between 24 - 32 weeks, chemotherapy exposure to the fetus must be balanced against risks of prematurity following elective delivery at that stage of gestation (Grade 1C). At gestation age more than 32 weeks, the fetus should be delivered prior to Induction chemotherapy.

Chemotherapy with anthracycline based regimens are favored. According to a meta-analysis done by Natanel A Horowitz et al, anthracycline based regimens were associated with maximum remission but overall maternal survival was very low (30%)[8]. Even in our case, although the mother immediately had remission with chemotherapy. There was a recurrence after disease free 10 months and she succumbed to the disease during the COVID pandemic. Quinolones, tetracyclines and sulphonamides are better avoided in pregnancy(Grade 1B).

In one case report by Abdullah et al, a trial of 5- azacytidine has shown promising results [9]. The antifungal of choice in pregnancy is Amphotericin B or lipid derivatives (Grade 2C). If blood transfusion is needed, the blood should be screened for Cytomegalovirus (Grade 1B). Supportive therapy like a course of Corticosteroids given if delivery is between 24 and 35 weeks gestation (Grade 1A) [10]. Magnesium sulphate should be considered 24 h prior to delivery before 30 weeks gestation (Grade 1A).

Delivery should be planned for a time when the woman is at least 3 weeks post-chemotherapy to minimize risk of neonatal myelosuppresion (Grade 1C). Planned delivery is preferred, like Induction of labour (Grade 2C). Caesarean section is indicated only for obstetric indications. Epidural analgesia is better avoided.

The Dose of chemotherapy is calculated on their actual body weight with dose adjustments for weight gain during pregnancy owing to various pregnancy changes.

The Chemotherapy agents have a MW of 250-400 KDa and hence can cross the placenta resulting in detrimental teratogenic effects on developing fetus.Sunny J. Patel et al have done a comprehensive analysis on outcomes in hospitalized pregnant patients with acute myeloid leukemia and come to conclusion that a multidesciplinary, holistic approach leads to quick remission of the disease [11]

After delivery, histopathologic examination of placenta to rule out placental transfer to fetus is advisable. Cytologic examination should be performed in both maternal and umbilical cord blood and neonates should be clinically examined for palpable skin lesions, organomegaly or other masses. If the baby is found to be healthy, a follow up after every six months for two years is recommended. In each visit, physical examination, chest x-ray and liver function tests should be done.