Introduction:
Approximately half of the annual cases of blood cancers are lymphomas, representing malignancies in the lymphatic system. The lymphatic system, comprising nodes in the neck, armpits, groin, chest, and abdomen, serves to eliminate excess bodily fluids and generate immune cells. Anomalies in lymphocytes (a subtype of white blood cells designed to combat infections) lead to the formation of lymphoma cells. These cells undergo multiplication and accumulate in the lymph nodes, gradually compromising the effectiveness of the immune system. Lymphoma may also be denoted as a form of immune system cancer.
What Is Lymphoma?
Lymphomas are classified as Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin lymphoma is diagnosed in approximately 12 percent of individuals with lymphoma, and advancements in research have transformed it from a once fatal condition to a manageable one. The majority of non-Hodgkin lymphomas are B-cell lymphomas, which can either be high-grade (growing rapidly) or low-grade (growing slowly). B-cell non-Hodgkin lymphomas encompass over a dozen distinct types. The remaining types are T-cell lymphomas, named after an alternative cancerous white blood cell, or lymphocyte. Lymphoma has the potential to impact individuals of any age, encompassing both adults and children.
What Does Relapsing Lymphoma Mean?
A relapse in lymphoma means the cancer has come back after successful treatment. To determine a relapse, doctors look for at least a 6-month period without any signs of lymphoma on tests and scans, which is called remission. If lymphoma shrinks during treatment but does not disappear completely (partial remission), the cells can grow again. Even in complete remission with no evidence of lymphoma on tests, there might still be a few hidden lymphoma cells. Certain types of lymphoma are more prone to relapse. Generally, low-grade non-Hodgkin lymphomas and certain high-grade non-Hodgkin lymphomas are more likely to relapse. Classical Hodgkin lymphomas, on the other hand, have a lower likelihood of relapse.
How Common Is Relapsing Lymphoma During Pregnancy?
Relapsing lymphoma during pregnancy is relatively uncommon, but it can occur, posing unique challenges for both patients and healthcare providers. The incidence of lymphoma during pregnancy is generally low, with estimates suggesting that it affects approximately 1 in 6,000 pregnancies. Among these cases, relapse during pregnancy is rarer still, but the exact prevalence is not well-documented. During pregnancy, managing relapsing lymphoma becomes more challenging because decisions about treatment need to consider the health of both the mother and the developing baby. Pregnant individuals with a history of lymphoma may face the risk of relapse, and this is influenced by factors like the type and stage of the lymphoma and the duration of remission. Treatment options have to be carefully chosen to ensure the best outcomes for both the mother and the baby.
What Are the Recommended Methods for Diagnosing Lymphoma in Pregnant Patients?
When investigating lymphoma, it is crucial to determine the stage of the disease to decide on the right treatment. While a tissue biopsy (taking a small sample for testing) can often be done with just local anesthesia, deeper structures may need a more involved procedure with general anesthesia. Using general anesthesia is generally considered safe during pregnancy and should not prevent getting a diagnosis. Procedures like bone marrow aspirates and trephines are also safe.
The usual process involves a full-body CT (computed tomography) scan or CT-PET scan to understand the extent of the disease before starting treatment. However, both of these techniques use a lot of radiation in the abdominal area, which is not safe during pregnancy. It is not yet clear if the substance used in PET (positron emission tomography) scans is safe during pregnancy, but it is known to cross the placenta. To reduce radiation to the fetus, some places use chest X-rays or CT scans with special shielding for the lower abdomen. Abdominal ultrasound can also be used for part of the staging. Many believe that MRI is safe during pregnancy and is a good alternative to full-body CT scans. If available, MRI is the best choice for imaging in pregnant patients, and ultrasound scanning is also safe and helpful.
Is Immunotherapy Considered Safe During Pregnancy?
A rapidly growing area of interest in blood cancer treatment is immunotherapy. This method uses specific biological agents that seem to work well and have few side effects because they target particular cells. One commonly used agent is Rituximab, which is a type of antibody targeting B-cells. However, because it can cross the placenta, there's a potential impact on the fetal B-cell population and the mother's healthy cells.
Rituximab has been used in pregnant individuals with both cancer and uncontrolled autoimmune diseases. Encouragingly, available data, including a case report, showed only a temporary loss of fetal B-cells due to exposure. No other reports have noted negative effects on the fetus.
Several other new immunotherapies are being tested. For example, Alemtuzumab targets CD52, and Epratuzumab recognizes CD22. Some experimental treatments involve modified antibodies linked to radioisotopes, showing promise in treating certain types of lymphoma that have returned. It is likely that in the future, both blood cancers and solid organ cancers will increasingly rely on this type of targeted therapy.
How Is Relapsing Lymphoma Managed During Pregnancy?
Restaging is necessary to evaluate the prognosis and direct the course of treatment. Prognostic models for relapsed Hodgkin's lymphoma (HL) are not as clearly defined as those for primary HL. A relapse following complete remission generally carries a more favorable prognosis than refractory disease, and a remission duration exceeding 12 months is associated with better outcomes. Factors indicating a poorer prognosis include a remission duration of less than 12 months, a late clinical stage, and the presence of anemia at the time of relapse.
The timing of treatment is a critical consideration. In some cases, treatment may be delayed until after the first trimester to reduce potential risks to the developing fetus. However, the decision depends on factors such as the type and stage of lymphoma, the gestational age, and the urgency of treatment. The common treatment approaches are mentioned below.
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Chemotherapy: Chemotherapy is a common treatment for lymphoma, but its use during pregnancy requires careful evaluation. Some chemotherapy drugs may pose risks to fetal development, especially during the first trimester. In certain situations, alternative chemotherapy agents or modified treatment schedules may be considered to balance the need for cancer control with fetal safety.
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Radiation Therapy: Radiation therapy is generally avoided during pregnancy, especially in the abdominal and pelvic regions, as it poses a risk to the developing fetus. If radiation is deemed necessary, techniques such as shielding or localized treatment may be employed to minimize exposure to the fetus.
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Fetal Monitoring: Continuous monitoring of the fetus is essential throughout the treatment process. Regular ultrasounds and other non-invasive techniques help assess fetal well-being and growth.
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Surgical Interventions: Surgical interventions may be considered depending on the type and location of the lymphoma. Whenever possible, procedures are conducted with the least impact on the fetus, and the potential risks and benefits are carefully weighed.
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Supportive Care: Supportive care measures, including medications to manage symptoms and side effects, are an integral part of managing relapsing lymphoma during pregnancy. This may include antiemetics to control nausea and vomiting associated with chemotherapy.
The choice of treatment depends on factors such as the trimester, location and stage of the disease, duration of remission, and the extent of prior therapy.
What Risks and Factors Should Be Considered in Different Management Options?
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For Hodgkin's lymphoma (HL) diagnosed after the first trimester, management options include observation, chemotherapy, and radiotherapy.
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Radiotherapy helps control local diseases but increases the risk of birth defects and childhood cancer.
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Chemotherapy in the first trimester may lead to miscarriage or major abnormalities, while later trimesters can result in growth issues, low birth weight, preterm birth, or stillbirth.
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Patients with limited, stable, and uncomplicated disease may defer treatment, allowing for comprehensive evaluation post-delivery and accurate stage-appropriate management.
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In cases where delaying treatment might harm the mother's survival, such as advanced disease in early pregnancy, emergency termination of pregnancy (TOP) may be considered due to increased teratogenic effects.
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Salvage therapy, involving high-dose chemotherapy, poses risks to the fetus, including spontaneous abortion, teratogenesis, and an elevated risk of childhood cancer.
Conclusion:
Hodgkin's lymphoma (HL) during pregnancy is rare and brings challenging decisions for both doctors and patients. When HL comes back (relapsed HL), it limits the options for imaging and treatments like chemotherapy or immunotherapy. If a pregnant person with a history of HL shows vague symptoms, doctors need to be extra vigilant. Emergency termination of pregnancy might be needed if delaying treatment could harm the mother's survival. If treatment is postponed until after childbirth, the woman should undergo further testing with a new biopsy and restaging.
