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Clinical Challenges: Managing Hodgkin’s in Pregnancy

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Clinicians who manage Hodgkin’s lymphoma patients with concurrent pregnancy navigate complex decisions to care for both mother and child.

Peak incidence of Hodgkin’s lymphoma coincides with female reproductive years, and approximately 0.5%-1.0% of all patients with the disease present with pregnancy. Overall, lymphoma is the fourth most common cancer occurring in pregnancy, but the most common hematologic malignancy.

“Any kind of illness impacting a woman during pregnancy has many implications, because we are considering both maternal and fetal health,” said Kelsey Martin, MD, a hematologist and medical oncologist at Yale School of Medicine in New Haven, Connecticut, who specializes in caring for pregnant patients.

Pregnancy in Hodgkin’s has not been shown to affect survival. In a study of 134 pregnant patients published in the Lancet Haematology, the overall survival rate at 5 years was 97% for those with early-stage disease and 100% with advanced illness, as compared to 98% and 96%, respectively, in a matched non-pregnant control group. Progression-free survival rates did not differ significantly as well.

Pregnant patients with earlier-stage illness may be able to defer treatment until later trimesters, or even after delivery. But for those with advanced disease, providers have one major challenge: preserving the health of the mother without harming the baby.

Clinicians must balance the effect of treatment delay on maternal survival, while taking into account the risk of unintended abortion, fetal malformation, or other poor perinatal outcomes that come with antenatal therapy.

Chelsea Pinnix, MD, PhD, and Loretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, told MedPage Today that one of the greatest challenges in treating Hodgkin’s lymphoma during pregnancy is diagnosis in the first trimester.

“Patients with advanced disease or those with extensive disease burden diagnosed in the first trimester are faced with a challenging situation,” Pinnix and Nastoupil said via email. “In this scenario, the disease can be life threatening such that delaying therapy may adversely impact survival of the pregnant patient.”

Due to the relative rarity of concurrent Hodgkin’s lymphoma and pregnancy, the medical literature is limited to case-control studies, retrospective reports, and expert opinions. Pinnix and Nastoupil said that there is a paucity of prospective data to guide clinical guidelines.

“The current literature that is available can help guide treatment decisions, but oncologists may have varying perspectives on the best way to manage patients during these challenging times,” they said.

Precautions in Diagnosis

As standard diagnostic tests for Hodgkin’s lymphoma using PET and CT imaging expose the fetus to high levels of radiation, they should be avoided during pregnancy, according to a review in Current Hematologic Malignancy Reports by Veronika Bachanova, MD, PhD, of University of Minnesota in Minneapolis, and Joseph Connors, MD, of BC Cancer Agency in Vancouver.

Histopathologic diagnosis should be obtained through an incisional or excisional biopsy, and patients should undergo normal bloodwork for hemoglobin, white blood cell count, platelet count, erythrocyte sedimentation rate, liver and renal function, as well as lactate dehydrogenase and serum protein electrophoresis.

Instead of PET-CT, the review authors stated that pregnant patients should receive one posteroanterior radiograph of the chest, with shielding to block radiation from harming the fetus.

Bachanova and Connors added that an abdominal ultrasound can be used to identify the size of retroperitoneal nodal disease. MRI without gadolinium, in addition, is a safe option for the fetus.

Initiating Treatment

Most pregnant Hodgkin’s lymphoma patients, Bachanova and Connors wrote, do not need immediate intervention.

Patients with early-stage disease can defer chemotherapy to the second or third trimester, when chemotherapy is less likely to be harmful to the baby. The fetus is most vulnerable between weeks 2 and 8 of gestation — when organ development begins.

Standard of care for Hodgkin’s lymphoma is multi-agent chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Retrospective studies have shown that ABVD is safe to use in the second and third trimester, as well as single-agent vinblastine.

Pregnancy management in Hodgkin’s lymphoma with bulky disease, visceral involvement, B symptoms, sub-diaphragmatic disease, or rapid disease progression, however, becomes more complicated.

Other medications for patients with advanced disease include brentuximab vedotin (Adcetris), an antibody-drug conjugate, and checkpoint inhibitors. But Martin stated that we do not have enough evidence about how those drugs impact pregnancy.

Additionally, the course of treatment depends on when a patient is diagnosed and how sick they are. For those diagnosed with advanced illness early in pregnancy, termination is likely a conversation that clinicians will have with their patient.

“These are hard conversations,” Martin said. Clinicians must be mindful of the cultural, religious, social, and ethical beliefs underlying this decision-making process, she said, and prioritize the emotional well-being of the patient.

Decision-Making at Delivery

When planning for delivery, Bachanova and Connors wrote that a maximal effort should be made to delay at least to 35-37 weeks’ gestation, to avoid preterm birth. According to the Lancet Haematology study, Hodgkin’s lymphoma patients who received antenatal therapy experienced more preterm contractions and preterm rupture of membranes.

Fernando Aguirre Amezquita, MD, a third-year maternal-fetal medicine fellow at the University of Minnesota Medical School in Minneapolis, said that there are a few complications to be mindful of during delivery. “Delivery is a time when there is potential for blood loss,” he said, adding that clinicians have to watch carefully for blood loss in patients with anemia or low platelet counts. Airway blockage that leads to respiratory issues is also a common complication for patients with bulky disease, he stated.

Martin said delivery should be delayed until 3 or 4 weeks after the last round of chemotherapy, to reduce the impacts of immunosuppressants on the baby after delivery. Breastfeeding after delivery should be discouraged if patients continue chemotherapy.

These patients receive multidisciplinary care from diagnosis to delivery to ensure that both the mother and her child receive optimal care. This team may consist of a hematologist-oncologist, maternal-fetal medicine specialist, general ob/gyn, neonatologist, anesthesiologist, pharmacist, and social worker.

“With a multidisciplinary approach, we can really create an individual plan for the patient,” Aguirre Amezquita said. “What’s important for these patients is to create a specific plan that will deliver the best care.”

  • Amanda D’Ambrosio is a reporter on MedPage Today’s enterprise & investigative team. She covers obstetrics-gynecology and other clinical news, and writes features about the U.S. healthcare system. Follow

https://www.medpagetoday.com/clinical-challenges/ash-hodgkin-related-lymphomas/90312

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