Clinical Advances in Hematology & Oncology
August 2013, Volume 11, Issue 8
Commentary
Hodgkin Lymphoma in Pregnancy: Achieving the Best Outcome for Both Mother and Infant
Freya Van Driessche, MD1, and Cesar A. Perez, MD2
1University of Miami Miller School of Medicine, Miami, Florida; 2James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
Hodgkin lymphoma (HL) occurs in a bimodal age distribution, with a peak in young adults and a peak in older age. The incidence of HL in the United States is 9,220 new cases per year, of which 4,220 are in women. Given that incidence peaks in the reproductive years, it is not surprising that 3% of women diagnosed with HL are pregnant.1 Sanchez and colleagues present a case of a 33-year-old woman who was diagnosed with stage IIA classical HL during the second trimester of an intrauterine pregnancy. Because of the timing of diagnosis, most of the treatment was delivered during pregnancy. The outcome was good in both mother and infant. Treating HL in a pregnant woman often presents diagnostic and therapeutic challenges to hematologists, as they must decide on the most beneficial course of action for both patient and infant. HL in pregnancy requires an interdisciplinary approach to the patient that involves medical oncology, maternal-fetal medicine, and pediatrics.
The first challenge is staging the pregnant patient. Staging of HL in the nonpregnant patient involves the use of positron emission tomography/computed tomography (PET/CT). Exposure of the fetus to less than 5 rads (0.05 Gy) is not associated with fetal congenital anomalies, growth restriction, intellectual disabilities, or miscarriage.2 However, 1–2 rads (0.01–0.02 Gy) of exposure may increase the risk of childhood cancer in the developing fetus by a factor of 1.5 to 2, although this finding is controversial.2,3 Fetal radiation exposure during nonabdominal CT scan is minimal. For example, a chest CT scan without the use of an abdominal shield exposes the fetus to 30 mrads (0.00003 Gy), far less than what could pose a safety risk to the fetus. Although a single anteroposterior chest radiograph with the use of an abdominal shield can be used for staging of the chest in HL, we recommend the use of chest CT with an abdominal shield, taking into consideration the radiation figures mentioned previously. Although the safety of using PET/CT in pregnancy has not been extensively studied, the exposure to the uterus using normal standard levels of isotope is 370–740 mrads (0.0037–0.0074 Gy). This is still well below the threshold of 5 rads (0.05 Gy), but the use of PET/CT in pregnancy is contraindicated because of the lack of studies.4
The second challenge faced is choice and timing of HL treatment. Currently, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is considered standard of care for classical HL because it has been demonstrated to have similar efficacy as mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), but with less toxicity.5 ABVD also appears to be safe to the fetus in the second and third trimesters of pregnancy, and is the recommended therapy in early-stage HL.6 On the other hand, for patients with unfavorable HL (stage IIB, III, or IV, or an International Prognostic Score of ≥3), dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) is advocated as the standard of care. However, since the difference between ABVD and dose-escalated BEACOPP in this high-risk population can be salvaged with a high-dose salvage regimen, we will recommend the use of ABVD even in this circumstance, because the toxicity of dose-escalated BEACOPP might compromise the infant.7
Treatment with chemotherapy in the first trimester remains controversial; some studies show that 33% of fetuses exposed in the first trimester are born with congenital abnormalities.8 Those patients with low-risk clinical circumstances (ie, slowly growing disease, disease above the diaphragm, diagnosis late in pregnancy) can have therapy delayed until after delivery without affecting long-term survival. To prevent delivery at a time where fetal myelosuppression would occur, chemotherapy should not be given within 3 weeks of scheduled delivery or after 35 weeks of gestation. This delay allows for fetal myelosuppression from chemotherapy to resolve and for the placenta to excrete any remaining drugs from the fetus.9
HL is a highly curable malignancy. The 10-year survival figures for HL are close to or exceed 90% in all age groups up to age 45 years.10 These figures are not affected if standard chemotherapeutic regimens for HL are administered during the second and third trimester.11 Long-term studies on children exposed to standard chemotherapy regimens for HL in utero have not shown increased rates of congenital anomalies, differences in birth weight or school performance, or increased rates of neurologic or psychologic problems. The children also did not have an increased rate of secondary malignancies.12 Standard treatment for low-risk HL in the second or third trimester with ABVD is associated with favorable maternal and fetal outcomes.11 Management of high-risk HL in pregnancy is less well described, but we advocate for use of ABVD in this population, along with a planned high-dose salvage regimen that includes autologous stem cell transplantation. Treatment within the first trimester of pregnancy remains controversial.
References
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