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Cancer in Pregnancy: Non-Hodgkin's Lymphoma and Pregnancy
Non-Hodgkin's lymphoma (NHL) is the fourth most common cancer among pregnant women1,2. It has an age-dependent incidence pattern with a sharp increase in frequency starting in middle life and occurs more frequently in young males. Taken together, these epidemiological data probably explain why there are so few reports on NHL in pregnancy. Available reports are mainly single cases of uncontrolled studies3,4. However, the rate of NHL has been increasing steadily in the last few years. To date more than 100 cases of NHL during pregnancy have been reported. A careful review of the cases that are published suggests that aggressive histology NHL is the most common type reported in pregnancy5,6.
Patients with NHL often have unusual manifestations and there is frequently a delay in diagnosis of up to three months7,8. The majority of pregnant women with NHL have diffuse large B-cell or peripheral T-cell lymphoma9.
The histologic presentation, the possible teratogenicity of some diagnostic methods and the need to administer combined chemotherapy regimens in these intermediate-high grade lymphomas dictate a limited staging work-up during pregnancy. This work-up should include history, physical examination, routine blood tests, bone marrow biopsies, chest x-ray with abdominal shielding, abdominal ultrasound and possibly MRI 5.
All patients diagnosed with NHL during the first trimester should be counseled regarding therapeutic abortion, and be staged and treated immediately with the standard therapy given to non-pregnant patient7. Local radiation therapy might be acceptable initially for only a small number of patients with stage I lymphoma9.
Treatment with a full dose of a multi-drug regimen should be administered during the second trimester10. In one report of 19 women, 16 healthy infants were delivered between 35 and 39 weeks of gestation with no apparent congenital abnormalities or complications of delivery, such as infection or bleeding10.
The use of radiolabeled monoclonal antibodies is contraindicated. The risk of other monoclonal antibodies (e.g., rituximab) during pregnancy is unknown.
Although Burkitt's and lymphoblastic lymphomas have been reported to have a rapid lethal course during pregnancy, the patients were probably not optimally treated with high-intensity, brief duration chemotherapy, according to current knowledge 12. High-dose methotrexate is an integral component of most effective regimes and poses the greatest risk to the developing fetus, especially if administered during the first trimester. Therapeutic abortion is strongly recommended, should this therapy by initiated. The rare pregnant women presenting with either low grade or localized intermediate grade lymphoma can be managed more conservatively.
Prognosis and fetal consequences
The effect of Non-Hodgkin's lymphoma on pregnancy (and vice versa), remains unclear. Some investigators observed rapid clinical progression of aggressive NHL during the immediate post partum period 6, while others concluded that pregnancy does not seem to affect the course of NHL9,13. Many reports suggest that the incidence of spontaneous abortion, malformation, and prematurity is not influenced by lymphoma9,14. In our own very small series, there appeared to be a trend towards a lower mean birth weight in babies born to mothers who had NHL compared to their matched controls 4. Recommendations regarding abortion should be individualized based on potential harm of staging procedures, chemotherapy or radiotherapy to the fetus 15. Induction of labor should be performed when there is a viable fetus and the mother's blood counts are not compromised by a recent cytotoxic treatment. Breast feeding is contraindicated during treatment of NHL 16. Placental involvement is uncommon but 4 cases have been reported, including 2 well-reported cases of dissemination to the fetus17,18.
- Haas JF: Pregnancy in association with a newly diagnosed cancer: A population-based epidemiologic assessment. Int J Cancer 34:229-235, 1984.
- Landis SH, Murray T, Bolden S, et al. Cancer Statistics, 1999. CA Cancer J Clin 49:8-31.
- Lishner M, Zemlickis D, Sutcliffe SB, Koren G: Non-Hodgkin's lymphoma in pregnancy, in: Cancer in pregnancy. Koren G,Lishner M,Farine D (eds). Cambridge University Press, pp. 116-119,1996.
- Lin AY, Tucker MA. Epidemiology of Hodgkin's Disease and Non-Hodgkin's lymphoma. In Canellos GP, Lister TA, Sklar (EDS): The Lymphomas. Philadelphia, Pa. 1998, pp. 43-61.
- Ward FT, Weiss RB: Lymphoma in pregnancy. Sem. Oncol 16:397-409,1989.
- Steiner-Salz D, Yahalom J, Samuelov A, Polliac A: Non Hodgkin's lymphoma associated with pregnancy. A report of 6 cases with a review of the literature. Cancer 56:2087-2091,1985.
- Pohlman B, Macklis M. Lymphoma and pregnancy. Sem. Oncol Vol27, No6, 2000.
- Moore DT, Taslimi MM: Non-Hodgkin's lymphoma in pregnancy: A diagnostic dilemma.Case report and review of the literature. J Tenn Med Assoc 85:467-469,1992.
- Dhedin N, Coiffier B: Lymphoma in the elderly and in pregnancy. In Canellos Gp, Lister TA, Sklar JL (eds). The Lymphomas. Philadelphia, Pa. Saunders, 1998, pp. 549-556.
- Aviles A. Diaz-Maguco JC, Torras V et al: Non-Hodgkin's lymphoma and pregnancy: Presentation of 16 patients. Gynecol Oncol 37:335-337,1990.
- Gelb AB, Van de Rijn M, Warnke RA, Kamel OW: Pregnancy associated lymphomas. A clinicopathological study. Cancer 78:304-310,1996.
- Selvais PL, Mazy G, Gosseye S et al: Breast infiltration by acute lymphoblastic leukemia during pregnancy. Am J Obstet Gynecol169:1619-1620,1993.
- Sutcliffe SB, Chapman RM: Lymphomas and leukemias. In: Cancer in Pregnancy (Allen HH, Nisker JA, ed.) Futura, mt kisco. pp135-189,1986.
- Zuazu J, Julia A, Sierra J, et.al: Pregnancy outcome in hematologic malignancies. Cancer 67:703-709,1991.
- Koren G, Weiner L, Lishner M, Zemlickis D, Finegen J: Cancer in pregnancy: Identification of unanswered questions on maternal and fetal risks. Obstet Gynecol Surv 45:504-514,1990.
- Doll DC, Ringenberg QS, Yarbro JW: Antineoplastic agents and pregnancy. Sem Oncol 16:337-346,1989.
- Antonelli NM, Dotters DJ, Katz VL, Kuller JA: Cancer in pregnancy: A review of the literature. Obstet & Gynecol Surv 51:125-142,1996.
- Meguerian-Bedoyan Z, Lamant L, Hopfner C, et al. Anaplastic large cell lymphoma of maternal origin involving the placenta: Case report and literature survey. Am J Surg Pathol 21:1236-1241,1997.