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Chapter 151 Hematologic Changes in Pregnancy 2209

highlights complications that may occur in pregnant women with Imatinib Therapy
Hodgkin disease because children born to three of five women with
the disease had complications, including death. Remission rates and A 38-year-old woman with a history of chronic-phase chronic myeloid
20-year overall survival rates among women diagnosed with Hodgkin leukemia on imatinib therapy for 5 years becomes pregnant. She has
disease during pregnancy are reportedly similar to those observed in had a complete cytogenetic response. She asks what to do about her
nonpregnant women with the disease. 143,144 In rare instances, Hodgkin imatinib therapy.
lymphoma metastasizes to the placenta, so the placenta and newborn Imatinib is teratogenic and should not be used during pregnancy. It
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infant should be examined for evidence of malignancy. Staging has been linked to spontaneous abortions and to fetal malformations,
during pregnancy can be performed with CT, but MRI is preferred including skeletal abnormalities, hydrocephalus, and exophthalmos.
to reduce to exposure of the fetus to radiation. Although there are case reports documenting fetal exposure at various
Similar to other malignancies managed during pregnancy, treat- stages of pregnancy without harm, it is not recommended. Case reports
ment of women with Hodgkin disease is challenging. Generally, suggest that patients who have achieved maximal response to therapy
fare better when their treatment is held for pregnancy, as opposed to
chemotherapy at any point in pregnancy increases the risk of an patients who have not achieved best response.
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unfavorable outcome. The teratogenic effects of chemotherapy and
radiation during pregnancy are a primary concern. However, the
standard regimen of Adriamycin (doxorubicin), bleomycin, vinblas-
tine, and dacarbazine does not appear to increase teratogenic risk teratogenicity in rats and impaired spermatogenesis in dogs, monkeys,
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when given in the second or third trimester. and rats. In a series of 19 pregnancies involving a mother or father
Non-Hodgkin lymphoma (NHL) rarely occurs during pregnancy. undergoing imatinib-based therapy for CML, three pregnancies
There are case reports and case series of women with NHL who have resulted in a spontaneous abortion, and two others produced children
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been treated successfully with chemotherapy during the second and with minor malformations. The remaining 13 pregnancies resulted
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third trimesters of pregnancy. In a review of 121 cases of pregnancy- in the delivery of a healthy child. Among mothers in this study who
associated NHL, 75% had stage IV disease at diagnosis, and repro- had previously achieved a complete hematologic remission with
ductive organ involvement was found in half the cases. Placental and imatinib and interrupted therapy during pregnancy, a majority (five
fetal involvement were uncommon. 146,147 of nine) lost the hematologic remission. These findings highlight the
Alkylating agents given during the first trimester can result in fetal important therapy-related implications for mother and fetus, which
malformations or death, although there are reports of children who must be weighed carefully in determining an appropriate course of
received chemotherapy during the first trimester with no subsequent management (see box on Imatinib Therapy). Currently, it is recom-
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deficits. On the basis of available data, response and recurrence mended by specialists in the field that patients undergoing treatment
rates among women treated for NHL during pregnancy are similar with imatinib for CML use proper contraception. 157
to those seen in the treatment of pregnant women with Hodgkin
disease.
The Myeloproliferative Neoplasms:
Acute and Chronic Leukemias Essential Thrombocythemia, Polycythemia
Vera, and Myelofibrosis
Treatment of acute myeloid leukemia cannot be delayed. Minimal
data are available on the treatment of patients with acute leukemia, Essential thrombocythemia (ET) has a bimodal peak of distribution,
but in patients treated with chemotherapy during the first trimester, so it is the most common myeloproliferative neoplasm (MPN) in
outcomes were poor. For patients in the first trimester, planned women of childbearing age (see Chapters 69, 70, and 71). Although
abortion should be discussed, followed by treatment with standard evidenced-based guidelines do not exist for the management of
induction chemotherapy. 149 pregnancy in this setting, more and more information regarding this
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Patients in the second and third trimesters should be treated topic is being reported. Although some variation is seen in the rates
immediately. There is an association of preterm delivery, IUGR, and of complications among various studies, overall, all of the studies
spontaneous abortion with treatment in the second and third trimes- noted a consistent increase in the rate of complications compared
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ters. In terms of treatment options, daunorubicin is preferred with pregnant women without MPN. Pregnancy alone is a risk
because idarubicin has increased placental transfer. Amphotericin B factor for thrombosis, and pregnancy confers a sixfold increase in the
is considered the antifungal of choice in pregnancy because there have rate of thrombosis in pregnant patients without MPN. Thrombosis
been no reports of teratogenicity. 151,152 If treatment is not delayed, is a major source of morbidity and mortality in patients with MPN.
pregnant women can have outcomes similar to those of nonpregnant It is thought that the prothrombotic state that exists in MPN is
patients. behind a majority of the morbidity that can develop during preg-
Among acute leukemias arising within the myeloid lineage, acute nancy. Thrombotic occlusion of the placental circulation has been
promyelocytic leukemia is unique in terms of clinical features, par- observed.
ticularly DIC and associated bleeding complications, and therapy, In a study documenting 103 pregnancies occurring in 62 patients
which involves all-trans retinoic acid (ATRA) in conjunction with with MPN, the rate of live births was 60%, and the first trimester
traditional chemotherapy. Concern regarding the teratogenic effects abortion rate was 32%. Fetal complications occurred in 40% of cases
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of ATRA is warranted. In the 1980s, Lammer and colleagues noted and maternal complications in 9%. The risk of fetal loss for patients
an increased risk of fetal malformation after in utero exposure to the with ET was 3.4-fold higher than for those in the aged-matched
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retinoid isotretinoin. In a recent case report, Carradice et al control population. 159
described a bleeding complication that occurred after ATRA initia- A pooled outcome analysis of 461 pregnant patients with ET
tion in a pregnant woman with acute promyelocytic anemia. However, demonstrated that first-trimester loss occurred in 25% to 40% of
authors of a review of 13 women treated during pregnancy with patients with a live birth rate of 50% to 70%. Late pregnancy loss
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ATRA administration for acute promyelocytic anemia found no occurred in 10% of cases. Postpartum thrombotic complications
evidence that the agent led to fetal malformation when used in the occurred in 5.2% of patients. In a recent analysis of all publications
treatment of pregnant women. 155 of pregnant patients with ET that had more than 30 patients per
Similar concerns regarding toxicity of therapy arise in managing study, a mean rate of live birth obtained from the literature was
pregnancies conceived before and during treatment of chronic 60.6% (range, 50%–75.4%). 161
myeloid leukemia (CML). Imatinib, a small-molecule inhibitor Studies of pregnancy in the setting of polycythemia vera (PV) are
against the BCR-ABL tyrosine kinase, is the standard of care much fewer and consist mainly of case reports. One of the largest
for treatment of CML. In animal studies, imatinib exhibited studies to date consisted of 18 pregnancies. There were 11 live births