A Case of Hematological Malignancy in Pregnancy: Therapeutic Complexities
A 29-year-old woman (G3P2) at 6 weeks of gestation presented to the emergency department for vaginal bleeding over the preceding few days. The patient reported passing blood clots and recent symptoms including easy bruising, unintentional weight loss of 70 pounds over three months, lightheadedness, intermittent headaches, and blurry vision. She denied fevers, chest pain, shortness of breath, abdominal pain, nausea, and vomiting. She also denied any history of prior malignancy. On arrival, she was hypertensive (blood pressure [BP]: 155/100 mmHg) and tachycardic (heart rate [HR]: 105 beats/min). Examination revealed scattered ecchymoses throughout her body. Otherwise, the results of the physical examination were unremarkable. Her family history was notable given a recent diagnosis of leukemia (unknown type) in her cousin. Admission labs were notable, with a white blood cell count (WBC) of 685 x 109/L, hemoglobin (Hb) level of 7 g/dL, and platelet count of 378 x 109 per liter. Automated differential on complete blood count (CBC) revealed 1% blasts, increased neutrophils, myelocytes, metamyelocytes, promyelocytes, basophils, and eosinophils. Pelvic ultrasound revealed an intrauterine pregnancy and a small subchorionic hemorrhage. She was transfused with one unit of packed red blood cells. Peripheral blood smear revealed leukocytosis with left shift and the presence of blasts. The hematology/oncology team was subsequently consulted.
The differential diagnosis for her leukocytosis included acute myeloid leukemia, chronic myeloid leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia.
She was ultimately diagnosed with chronic myelogenous leukemia (CML), confirmed via bone marrow biopsy and aspiration, as well as by an evaluation of BCR-ABL using fluorescence in situ hybridization (FISH) and PCR. Subsequently, she underwent one round of leukapheresis. She was started on pegylated interferon at 180 mcg every five days and pulsating doses of oral hydroxyurea at 1 g for 5 days. As of her most recent follow up, she is clinically stable and doing well.
CML is a myeloproliferative neoplasm caused by a reciprocal translocation between chromosomes 9 and 22, with an incidence of one to two cases per 100,000 adults. This translocation leads to the fusion of the ABL1 gene on chromosome 9 and the BCR gene on chromosome 22.1 The BCR/ABL1 gene codes for an active tyrosine kinase that activates multiple signaling pathways, leading to malignancy. Patients can present with a variety of symptoms including weight loss, fatigue, night sweats, and hepatosplenomegaly. Patients typically have leukocytosis, along with anemia and thrombocytosis.2
Tyrosine kinase inhibitors are the firstline treatment for CML. These drugs target the enzyme that drives the abnormal proliferation of cells. Other treatment options include interferon alpha and hydroxyurea. Busulfan has also been used in the past.3
Since tyrosine kinase inhibitors are teratogenic, management of pregnant patients with CML presents a challenge. Review of the literature suggests that there have been cases in which pregnant women with CML were successfully treated with pegylated interferon alpha during their first trimester (similar to our patient) and continued on the treatment until delivery.4 Interferon alpha inhibits cellular growth and proliferation without directly inhibiting DNA synthesis.4,5 Further, interferon alpha does not cross the placenta and additionally enhances immune regulation and modulates hematopoiesis in the bone marrow.6 Leukapheresis can also be considered to reduce cell counts in symptomatic patients, as in our patient.
Moreover, aspirin or low-molecular-weight heparin (LMWH) can be considered for thrombosis prevention when the platelet count exceeds 500 x 109.7 Side effects of interferon alpha treatment include hematologic toxicity, flu-like symptoms, elevated transaminase levels, fatigue, nausea, and psychiatric manifestations.8
Management of CML can be difficult in pregnancy due to the teratogenicity that is associated with the firstline treatment agents. According to prior cases of CML in pregnancy documented in the literature, interferon alpha and leukapheresis are effective alternatives.
COI Disclosure: Rabab Jafry and Dr. Hina Khan indicated no relevant conflicts of interest.
This article was edited by Drs. Sydney Dunn-Valadez and Usha Perepu.
References:
1. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol. 2020;95(6):691-709.
2. Osman AEG, Deininger MW. Chronic myeloid leukemia: Modern therapies, current challenges and future directions. Blood Rev. 2021;49:100825.
3. Rinaldi I, Winston K. Chronic myeloid leukemia, from pathophysiology to treatment-free remission: A narrative literature review. J Blood Med. 2023;14:261-277.
4. Mubarak AA, Kakil IR, Awidi A, et al. Normal outcome of pregnancy in chronic myeloid leukemia treated with interferon-alpha in 1st trimester: Report of 3 cases and review of the literature. Am J Hematol. 2002;69(2):115-118.
5. Talpaz M, Hehlmann R, Quintás-Cardama A, et al. Re-emergence of interferon-α in the treatment of chronic myeloid leukemia. Leukemia. 2013;27(4):803-812.
6. Castillo DR, Park D, Mehta A, et al. Outcomes of the pregnancies with chronic myeloid leukemia in the tyrosine kinase inhibitor era and literature review. Hematol Rep. 2022;14(1):45-53.
7. Lishner M, Avivi I, Apperley JF, et al. Hematologic malignancies in pregnancy: Management guidelines from an international consensus meeting. J Clin Oncol. 2016;34(5):501-508
8. Sleijfer S, Bannink M, Van Gool AR, et al. Side effects of interferon-alpha therapy. Pharm World Sci. 2005;27(6):423-431.
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