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Cancer in Pregnancy: Leukemia during Pregnancy

Introduction
The occurrence of leukemia during pregnancy is very rare with an estimated incidence of one per 100,000 pregnancies annually1. It has been estimated that during pregnancy most leukemias are acute: two thirds are myeloid (AML) and one third are lymphatic (ALL) 2. Chronic myeloid leukemia (CML) is found in less than 10% of leukemias during pregnancy 2 and chronic lymphocytic leukemia (CLL) is extremely rare 3.

Prognosis
The survival of pregnant and non-pregnant women with acute leukemia has improved with the availability of modern chemotherapy and supportive care. Remission rates of 70-75% and median survival time of 6 to12 months are currently reported for pregnant women 4,5. These figures are not different from those achieved in non-pregnant women with acute leukemia.

Fetal consequences
Acute leukemia can affect pregnancy and the fetus. Intrauterine growth retardation has been reported in mothers not treated with chemotherapy 4. In addition, preterm labor, induced and spontaneous abortion as well as still birth are common in acute leukemia 2,5. Although there is an estimated teratogenic risk rate of 10% when chemotherapy is administered in the first trimester, Avile's and Niz reported no fetal malformations and no late side effects in children born to mothers who were treated for acute leukemia during early pregnancy 6.

Treatment

It is generally believed that pregnant women should be treated as non-pregnant women.

Therapeutic abortion should be considered in early gestation, but if the woman decides to continue the pregnancy certain drugs, like methotrexate, should be replaced. Standard anti-leukemic treatment can be safely administered during the second and third trimesters. Delivery should be accomplished when fetal survival can be ensured and the mother is in complete remission 7. There are rare reports of leukemia blasts infiltrating the placenta 8 and a single case of infantile acute monocytic leukemia caused by vertical transmission of the mother's leukemia cells 9.

Five cases of relapse of ALL in pregnancy have been reported in the English-language medical literature. The mechanisms attributable to the immunologic and hormonal changes of pregnancy have been postulated 10. All five patients were treated between 2 weeks and 4.5 months with cytotoxic chemotherapy with the fetus still in utero. Four out of five patients delivered healthy and normal infants and an elective abortion was reported. Unfortunately, all mothers except one died of their disease in under 2 years 10.

Giagounidis et al reviewing the literature, identified 14 cases of children born from mothers with APL and treated with ATRA (all-trans-retinoic acid) in the second and third trimester of gestation. One baby had Potter's Syndrome diagnosed before onset of ATRA. None of the other babies was born with malformations. Six of the children were born without any obstetric complications, while two babies had cardiac symptoms at birth but survived without sequelae. Two other babies delivered by cesarean section had low Apgar scores at 1 minute and 5 minutes, one developed respiratory distress because of anesthetic applied to the mother, one baby delivered prematurely, and one stillbirth occurred at 29 weeks 11.

Chronic myeloid leukemia during pregnancy should be treated as in the nongestational patients. Since the disease has an initial chronic phase, it is usually managed conservatively during pregnancy, while an aggressive approach, such as bone marrow transplantation, may be considered after delivery. A limited number of cases described successful treatment modalities of CML during pregnancy including leukapheresis 12, 13, hydroxyurea 14, 15 and interferon 16, 17.

Pregnancy complicated by hairy cell leukemia is extremely rare. Splenectomy is a safe and effective treatment option during the second trimester for this rare condition 18

Single cases have been treated with interferon during pregnancy 12. A single case of CLL was reported 3. Interestingly, the placenta showed increased numbers of mature appearing lymphocytes in the intervillous space, consistent with the diagnosis of CLL. The baby was small for date but had no malformations and had an uneventful post partum course.

References

  1. Haas VA: Pregnancy in association with newly diagnosed cancer: a population-based epidemiological assessment. Int J cancer 34:229-235,1984.
  2. Calligiuri MA, Mayer RJ: Pregnancy and leukemia. Sem Oncol 16:338-396,1989.
  3. Chrisomalis L, Baxi LV, Heller D: Chronic lymphocytic leukemia in pregnancy. Am J Obstet Gynecol175:1381-2,1996.
  4. Catanzarite VA, Ferguson JE: Acute leukemia and pregnancy: a review of management and outcome. Obstet Gynecol Surv 39:663-678,1974.
  5. Reynoso EE, Sheperd FF, Messner HA et al: Acute leukemia during pregnancy. The Toronto Leukemia study group experience with long-term follow-up of children exposed in utero to chemotherapeutic agents J. Clin Oncol 5:1098-1100,1987.
  6. Aviles A, Niz J. Long-term follow-up of children born to mothers with acute leukemia during pregnancy. Med & Ped Oncol 16:3-6,1988.
  7. Lishner M, Ravid M. Leukemia during pregnancy. In: Cancer in pregnancy: maternal and fetal risks. Koren G, Lishner M, Farine D (eds). Cambridge University Press. pp. 143-146,1996.
  8. Diddy III GA, Moise Jr KJ, Carpenter Jr RJ et al. Maternal malignancy metastatic to the products of conception: A review. Obstet Gynecol Surv44:535-540,1989.
  9. Osada S, Horbe K, Oiwa K et al. A case of infantile acute monocytic leukemia caused by vertical transmission of the mother's leukemia cells. Cancer 65:1146-1149,1990.
  10. Krishnansu Tewari, Fabio Cappuccini, Robert B. Rosen, Tamerou Asrat, Matthew F. Kohler. Relapse of acute lymphoblastic leukemia in pregnancy: survival following chemoirradiation and autologous transfer of interleukin-2-activated stem cells. Gynecologic Oncology 74, 143-146, 1999.
  11. Giagounidis AAN, Beckmann MW, Giagounidis AS, Aivado M, Emde T, Germing U, Riehs T, Heyll A, Aul C. Acute promyelocytic leukemia and pregnancy. Eur J Haematol 64: 267-271, 2000.
  12. Bazarbashi MS, Smith MR, Karaner C, ZielinskiI, Bishop CR: Successful management of Ph chromosome positive chronic myelogenous leukemia with leukapheresis during pregnancy. Am. J. Hematol 38:235-7,1991.
  13. Frank J. Strobl, Karl V. Voelkerding, Eileen P. Smith. Management of chronic myeloid leukemia during pregnancy with leukapheresis. Journal of Clinical Apheresis 14:41-44, 1999.
  14. Patel M, Dukes IA, Hull JC: Use of hydroxyurea in chronic myeloid leukemia during pregnancy: A case report. J Repro Med 33:661-3,1988.
  15. Murat Celiloglu, Sabahattin Altunyurat, Bulent Undar. Hydroxyurea treatment for chronicmyeloid leukemia during pregnancy. Acta Obstet Gynecol Scand 79:803-804, 2000.
  16. Baer MR, Ozer H, Foon KA: Interferon - a therapy during pregnancy in chronic myelogerous leukemia and hairy cell leukemia. Br J Hemato l81:161-9,1992.
  17. C. Baykal, N. Zengin, F. Coskun, N. Guler, A. Ayhan. Use of hydroxyurea and alpha-interferon in chronic myeloid leukemia during pregnancy: a case report. Eur J Gynaec. Oncol, 2000.
  18. Stiles GM, Stanco LM, Saven A, Hoffmann KD. Splenectomy for hairy cell leukemia in pregnancy. J Perinatol May-June; 18(3): 200-1, 1998.
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