Chronic Lymphocytic Leukemia

The incidence of chronic lymphocytic leukemia (CLL) during pregnancy is rare, as this malignancy affects mainly the older population, with a median age of approximately 70 years, and it affects men twice as often as women. Only 10-15% of patients are under the age of 50 years.74 The management of CLL in the pregnant patient is challenging due to lack of data. Information regarding the effects of various chemother-apeutic agents on the developing fetus is derived solely from reports describing teratogenic and mutagenic effects in animal experiments, and case reports on pregnancy outcomes complicated by various other malignancies. Only four cases of pregnancy and CLL have been described.75-78

The natural course of CLL can be highly variable, and chemotherapy is often not indicated if the disease is in an early and stable stage, as there is no data to support improvement in survival with early interven-tion.79 Therefore, CLL may not require treatment immediately because it has a relatively indolent course, but it can carry a risk of leukostasis, as well as risk of placental insufficiency, IUGR, increased fetal prematurity, and increased mortality.80 Leukapheresis has been successfully used in both acute and chronic leukemias for rapid reduction of high WBC counts in patients with symptoms of increased viscosity. This form of treatment provides a temporary alternative to chemotherapy for the pregnant patient with signs/ symptoms of leukostasis.81-83

In a case reported by Chrisomalis et al.,75 a 30-year-old woman with CLL experienced repeated infections during pregnancy that were treated successfully with antibiotics. She was not treated for the CLL, as she was asymptomatic. In addition to her bone marrow, the intervillous spaces of the placenta were filled with mature-appearing lymphocytes consistent with CLL. The patient delivered a healthy newborn, and the patient and baby remained in good health 1 year after delivery.75 Welsh et al.76 reported a 22-year-old patient with CLL diagnosed at 35 weeks gestation with a WBC count of 45,400/^L. She delivered a healthy infant at term. Four months following delivery, her WBC count decreased to 10,300/^L without therapy. She continued to have a high percentage of monoclonal lymphocytes, but the absolute number decreased. The authors concluded that this represents an apparent spontaneous "clinical" but not "clonal" regression.76

Ali et al. published a case of a 30-year-old woman who presented with anemia and cervical lym-phadenopathy in the 17th week of gestation.78 Based on clinical findings, and microscopic analysis of her peripheral blood and bone marrow, she was diagnosed as having stage IV B-cell CLL. The patient underwent three courses of leukapheresis at the 25th, 30th, and 38th weeks of gestation to maintain the WBC count below 100,000/^L. Therapeutic pheresis was well tolerated by the mother and fetus, and no complications were identified. A healthy baby was born at term without anatomical or hematologic abnormalities.

There have been no reports on the use of purine analogues in pregnancy.

Targeted therapy with an anti-CD52 or anti-CD20 monoclonal antibody has been used in untreated CLL patients and in those with progressive disease after flu-darabine treatment.8485 Rituximab is one such anti-CD20 monoclonal antibody, and there exists little evidence for its safety during pregnancy. One report on rituximab and pregnancy has been published in a non-Hodgkin's lymphoma patient. A 29-year-old female with stage IIA bulky CD20T diffuse large B-cell lymphoma was treated with rituximab during 21 weeks of gestation. She received four cycles of therapy along with doxorubicin, vincristine, and oral prednisolone. The patient developed a very good partial remission and subsequently delivered a healthy term infant by Cesarean section. The child developed normally, and a normal peripheral B-cell population was detected at 4 months.86

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