Acute Lymphocytic Leukemia (ALL) in Pregnancy, Case Report and Literature Review

Introduction: Leukemia is rare in pregnancy, occurring in up to 1 in 100,000 pregnancies. A 28F G2P1 was diagnosed at our institution with Philadelphia (Ph) negative B-ALL at 24 weeks' gestation. She was induced with UKALL14 and achieved a flow negative complete remission post-induction. During induction chemotherapy, regular ultrasound scans showed that the fetus was growing normally for gestational age. The patient was kept on weekly vincristine and prednisone and had an elective c-section at 31+3 weeks, in light of her previous caesarean section, poor bishop score, and in order for her to safely resume chemotherapy. Baby girl had an uneventful hospital course and was discharged after 29 days. Given the sparse data on this challenging topic, we decided to review the literature for all reported cases of ALL in pregnancy.

Methods: We reviewed the literature for all reported cases of ALL from 2000 to 2023. We collected available data on the patient, pregnancy, and fetal outcome as well as leukemia characteristics and chemotherapy received.

Results: We found 57 patients across 20 studies. The median age at diagnosis was 26 years (range 16-41 years). Most affected pregnancies were during the second trimester (T2) (n 23/57) and third trimester (T3) (n 20/57). The subtype of ALL was reported in 49 patients; of those, B ALL was the most common (n 35/49). Ph was reported positive in eight patients. A total of 53 patients received chemotherapy, of those 33 patients were received during pregnancy, while 13 were after pregnancy, and the remaining 7 had unclear timing. Patients received different combinations of standard ALL chemotherapy agents including vincristine (n 49/53), cyclophosphamide (n 25/53), prednisone (n 42/53), dexamethasone (n 23/53), L-asparaginase (n 20/53), pegaspargase (n 1/53), daunorubicin (n 36/53), doxorubicin (n 7/53), idarubicin (n 4/53), cytarabine (n 11/53), 6-mercaptopurine (n 8/53), cytosine arabinoside (n 1/53), and methotrexate was given to 8 patients intrathecally during pregnancy; 6 during T2 and 2 during the first trimester (T1). Dasatinib and imatinib were given to two patients at 33 and 24 weeks respectively. There were no reports of patients who were treated with immune therapy while pregnant.

All four patients who did not receive any treatment died from progressive disease. Complete remission (CR) was reported in 45 patients. One patient died during induction from septicaemia, five were refractory to induction chemotherapy and 2 did not have induction outcome reported. Of those who achieved a CR, 21 were reported alive and 16 reported dead at last follow up. Among those mortalities, 8 were due to relapsed leukemia, 3 due to infectious causes, 2 due to respiratory failure and 2 from unspecified causes. Five patients were reported to have persistent or refractory leukemia, 4 of whom died.

Among the 14 T1 pregnancies, 10 were terminated electively, 3 spontaneously, and there was one maternal death due to declining treatment. Three patients received chemotherapy during T1, two suffered a spontaneous abortion and one had a missed miscarriage. Among the 23 T2 pregnancies, 17 resulted in live deliveries, one stillbirth during chemotherapy, one maternal death and 4 spontaneous abortions; 2 of which received chemotherapy during pregnancy, one did not receive treatment and one abortion with unclear timing of chemotherapy initiation. Among the 20 T3 pregnancies, 19 had successful deliveries and one stillbirth at an unindicated gestational age after receiving chemotherapy. Five babies were reported to have low birth weight, four had neonatal cerebral ischemia, one had intraventricular hemorrhage and one suffered from intestinal obstruction 2 weeks after delivery. All babies were discharged from hospital with no adverse congenital or developmental complications.

Conclusion: Treatment of women presenting with ALL at or beyond T2 is possible with high early remission rates for the mothers and delivery of healthy babies. The outcome is highly dependent on the gestational age. It is important that more cases are reported on this topic due to its challenging and multidisciplinary nature especially given the sparse data available and potential for reporting bias.