The Management of Myeloproliferative Neoplasms in Pregnant Women

Naseema Gangat, MD, MBBS

Treatment of myeloproliferative neoplasms (MPNs) can come with many challenges for the patient and their treating physician. When these diseases occur in women who are pregnant, the challenges are unique and require an individualized approach.

At the Mayo Clinic, a group of hematologists studied the pregnancy outcomes of 102 women with MPNs and found that despite the growing numbers of pregnant patients who develop myeloproliferative diseases, the live birth rates have improved since 2008 within the institution. This is reportedly due to hematologists at the Mayo Clinic collaborating with the Obstetrics Department to address all aspects of patients’ disease.¹ The findings from the small single-institution study, led by Naseema Gangat, MD, MBBS, et al, provided practice recommendations for hematologists treating pregnant women with MPNs in a paper published in the American Journal of Hematology.

The paper reviewed the outcomes observed in pregnant patients who had essential thrombocytopenia, polycythemia vera, and myelofibrosis. The authors then provided recommendations for physicians treating MPNs during preconception and post-conception as well as postpartum management.²

In an interview with Targeted Oncology, Gangat, consultant, Division of Hematology, Department of Internal Medicine, and associate professor of medicine, Mayo Clinic, discussed her recommendations for managing pregnant patients with MPNs.

TARGETED ONCOLOGY: Can you explain what MPNs look like in the general population? How are MPNs different in pregnant women?

Gangat: MPNs [are] a vast field. Essential thrombocytopenia, polycythemia vera, and myelofibrosis are the big subgroups within MPNs. For pregnant women, MPNs can be critical, particularly because of the risk of thrombosis. A lot of factors come in; for example, patients may need cytoreductive therapy like chemotherapy, [and[ the treatment has to be safe enough for the baby.

It is also important to know whether they have had blood clots before. If we have a young patient with a new diagnosis, we will often counsel them about what role this disease plays in terms of their ability to conceive and what precautions to take, what kind of monitoring they need, even before they become pregnant.

Which MPNs appear to be the most challenging for pregnant patients?

In general, if you look at the breakdown among young patients who are below 40 years of age, essential thrombocytopenia is the most common MPN. So, that is more dangerous in the sense there's risk of bleeding and thrombosis. Thrombotic risk is also high with polycythemia vera, and even though that's more prevalent in older patients, there will be a subset of younger patients who have polycythemia vera, so it has to be factored in.

For patients with essential thrombocytopenia and polycythemia vera, we have to be mindful of pregnancy losses and maternal complications in terms of bleeding and thrombosis, both antepartum and postpartum. These patients need very specialized care.

In the context of myelofibrosis, which is the most aggressive of these diseases, pregnancy is very rare. There are very few cases reported. We don't worry too much about thrombosis in those instances.

In your practice, can you describe what a multidisciplinary team looks like for a pregnant patient with an MPN? How do these clinicians work together?

The multidisciplinary team would include both the hematologist and the high-risk obstetrics department. From the hematological perspective, we would make sure to go through the scans monitoring to make sure, for example, if it's a patient with polycythemia vera, things like their hematocrit are maintained, so that there’s no risk of thrombosis. Obstetrics would keep a close eye on the maternal complications such as preeclampsia and fetal growth charts. Overall, if managed in the appropriate fashion, these women are able to have multiple pregnancies with little risk of complication.

What are your key practice recommendations for treating pregnant patients with an MPN?

Since we don’t have the best evidence due to the lack of clinical trials. There are no prospective studies in the United States where patients have been followed over time and there’s only 1 prospective study from the United Kingdom in which they reported live birth in about 58 patients with an MPN, but the rest are retrospective data.

Based on my experience at the Mayo Clinic having managed several pregnant patients with MPNs. We did share our experience last year in the in 55 pregnant patients with essential thrombocytopenia. What we learned was that we do want to re-stratify our patients based on their risk for thrombosis. Automatically, if a woman has had a prior thrombosis event or a prior pregnancy complication, they are in the high-risk group. Those are patients that would need baby aspirin for sure, and potentially on cytoreductive chemotherapy in the form of pegylated interferon, which is safe to use in the first trimester and thereafter.

If they had a prior venous thrombosis such as a deep vein thrombosis or pulmonary embolism, then we would recommend anticoagulation as well. So, the management of those patients needs to be very stringent.

The low-risk patients are those with no prior pregnancy complications and absence of a JAK2 mutation. Those are the patients that may or may not need aspirin alone. Some of these patients can even undergo observation alone. Since we do know from general research about patients with MPNs in general that JAK2 mutations confers an increased risk of thrombosis and also could potentially play a role in increasing pregnancy complications, those patients should definitely be on an aspirin a day. The exact dosage has not been widely studied.

If you look at polycythemia vera, pregnancy is not very common. So, all the pregnancies in general are high risk and the risk for thrombosis and polycythemia vera is definitely higher than in essential thrombocythemia. In these cases, frequent phlebotomy is recommended to keep an eye on the patient. For those with prior thrombosis, we would definitely recommend cytoreductive chemotherapy.

I would say each pregnant woman with an MPN needs to have individualized care. Hematology and obstetrics look for different things in terms of risk. So, we would want to optimize them, from every angle, so that [they are] least likely to [have] morbidity to the fetus as well as to the mother.

What is the key takeaway from your paper in the American Journal of Hematology ?

What I tried to do in this paper was to bring everything together, synthesize the material and give my interpretation of the findings, so that it can be a useful document for people who are managing MPNs and pregnancy. Then we left off with the algorithm in paper to highlight very briefly how we would categorize our patients and what kind of management recommendations we would need for the practitioners.

_References:

_{1 Gangat N, Joshi M, Shah S, et al. Pregnancy outcomes in myeloproliferative neoplasms: A Mayo Clinic report on 102 pregnancies. Am J Hematol. 2020; 95(5):E114-E117. doi: 10.1002/ajh.25748.}

_{2. Gangat N and Tefferi A. Myeloproliferative neoplasms and pregnancy: Overview and practice recommendations. Am J Hematol. 2021; 91(3): 354-366. doi: 10.1002/ajh.26067}