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124 Part III: Epochal Hematology Chapter 8: Hematology during Pregnancy 125

scans can probably be done safely in pregnancy; however, this is rarely ACUTE LEUKEMIA
necessary and most experts recommend waiting until after the first tri- Leukemia is distinctly uncommon in pregnancy; estimates derived from
mester. The toxicities of treatment and the risks of delaying treatment studies beginning in the 1950s place the incidence at approximately
until later in pregnancy or postpartum need to be considered carefully 1:75,000 pregnancies (Chaps. 88 and 91). 119,120 Acute leukemias make
in each case. Fetal risks of chemotherapy are greatest in the first tri- up nearly 90 percent of the total, followed by chronic myeloid leukemia,
mester during the period of organogenesis, with folate antagonists and which comprises an additional 10 percent; chronic lymphocytic leuke-
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antimetabolites carrying the largest risk. Despite the changes in phys- mia is extremely rare. The acute leukemias require urgent treatment,
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iology that occur during pregnancy, there is no evidence that dosing and while pregnancy itself does not alter the course of the leukemia,
should be changed. If chemotherapy is indicated, it should be delayed the outcome is much worse if treatment is delayed. A summary of
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until the second trimester; however, single-agent vinblastine has been data on 96 pregnant women reported in the literature from 1983 to 1995
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given in the first trimester with a low incidence of fetal abnormalities. who were treated with cytotoxic chemotherapy for leukemias (most of
Treatment should be timed so that there is the maximum amount of which were acute) revealed that most patients received regimens that
time possible between the last dose of chemotherapy and delivery to included multiple drugs and were not different from those given to
avoid cytopenias in either the mother or the fetus. In some cases, radio- nonpregnant patients. Nearly one-third of patients were treated in
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therapy may be a feasible alternative in the second and third trimesters the first trimester of pregnancy. Among the 96 pregnancies, there were
of pregnancy. Of 16 patients who received radiotherapy for supradia- 2 maternal deaths, 2 children were stillborn, 2 therapeutic abortions
phragmatic Hodgkin lymphoma (clinical stages IA and IIA) during were performed, 1 child had chromosomal abnormalities, and 8 had
pregnancy, 11 received full mantle irradiation, and all patients had congenital defects. Seven of the eight children born with congenital
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lead shielding of the uterus. All 16 pregnancies were carried to com- defects were born to mothers who had been treated in the first trimes-
pletion with full-term deliveries of normal infants. However, a review ter. It was not possible to identify a drug (or drugs) that was most likely
of the records of 382 women treated with radiotherapy for Hodgkin responsible for adverse outcomes. Treatment in the first trimester carries
lymphoma suggests that the risk of breast cancer after radiation ther- a high risk of fetal anomaly or miscarriage. For patients with acute mye-
apy is nearly sevenfold greater with irradiation around the time of logenous leukemia (AML) receiving a standard induction regimen of
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pregnancy. Additional studies are needed to confirm these findings, cytarabine and an anthracycline, it is probably best to avoid idarubicin,
but this potential risk should be borne in mind by the clinician when which is more lipophilic with elevated placental transfer. Doxorubicin
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making therapeutic decisions. Relapse of Hodgkin lymphoma usu- has been extensively studied in pregnancy women with breast cancer
ally occurs within the first 2 years following treatment, and patients are and is probably the anthracycline of choice in pregnant patients with
counseled to avoid pregnancy during this period. Vigilance for second AML. Although few cases of fetal cardiotoxicity related to anthracy-
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cancers in these patients is also advised as is monitoring for hypothy- clines have been reported, fetal cardiac function should be monitored in
roidism in those who receive radiation therapy, especially during subse- pregnancy. Very few data exist for consolidation therapy in pregnancy.
quent pregnancies when hypothyroidism could have profound maternal Case reports of treatment of acute promyelocytic leukemia in preg-
and fetal effects.
nancy with all-trans-retinoic acid 125–127 suggest that it may be safe after
NON-HODGKIN LYMPHOMA the first trimester. Arsenic trioxide is not recommended for use at any
stage of pregnancy because of its high potential for embryotoxicity.
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As compared with Hodgkin lymphoma, other lymphomas (Chap. 95) For patients who require chemotherapy postpartum, breastfeeding is
are less frequent in pregnancy, tend to present with a higher stage dis- not recommended so as to avoid exposure of the newborn to cytotoxic
ease, and have a poorer prognosis. Burkitt or Burkitt-like lymphoma drugs in the breast milk. Patients with chronic myeloid leukemia have
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can involve the breasts of young pregnant or lactating women and typ- been successfully treated in pregnancy with interferon-α, hydroxyurea,
ically behaves aggressively. 111,112 A recent review of more than 100 cases leukapheresis, and even busulfan. 130–132 A review of 125 women treated
of Non-Hodgkin lymphoma in pregnancy, 75 percent of the patients with imatinib mesylate during pregnancy revealed that most pregnan-
had stage IV disease at diagnosis and nearly half had involvement of cies had successful outcomes; however, 12 infants had abnormalities, 3
reproductive organs, primarily the breast. Very few cases of placental or of which involved complex malformations. 133
fetal involvement were observed. In patients with high-grade lympho- Supportive treatment with antiemetics, including ondansetron,
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mas, chemotherapy often cannot be delayed and difficult decisions must aprepitant and metoclopramide, is safe, and these agents do not cause
be made. However, in one report of 16 pregnant patients who received congenital malformations. Little data exist for the effects of growth
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aggressive chemotherapy for non-Hodgkin lymphoma during their factors including granulocyte colony-stimulating factors, but there are
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pregnancies, all survived to delivery. Half of the 16 patients received no reports of teratogenic effects. Care should be taken with prescrib-
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chemotherapy in their first trimester and all 16 delivered healthy ing antibiotics and quinolones in specific should be avoided in preg-
infants despite episodes of myelosuppression during the pregnancies. nancy as should sulfonamides. When antifungal therapy is required,
In a subsequent report, the health of 84 children born to mothers who amphotericin may be the drug of choice as there have been no reports
received chemotherapy for hematologic malignancies during pregnancy of teratogenicity with this agent. Fluconazole appears to be safe at doses
revealed no abnormalities in physical or cognitive development and no less than 150 mg per day, but ketoconazole and voriconazole can cause
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increase in cancers at a median followup of 18.7 years. Rituximab in fetal malformations and should avoided altogether. 136
pregnancy, both as a single agent and in combination with chemother-
apy, has not been associated with abnormalities of the newborn when
given in the first, second, or third trimester ; however, there is one ESSENTIAL THROMBOCYTHEMIA
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report of prolonged lymphopenia in a neonate whose mother received
rituximab in pregnancy. 61,116,117 A retrospective study of 231 pregnancies The management of pregnant patients with essential thrombocythe-
associated with maternal rituximab exposure identified 153 pregnan- mia (ET) is a challenge because thrombosis is the main complication
cies with known outcomes. Among these pregnancies there were 90 live of ET (Chap. 85) and is accentuated by the prothrombotic state of preg-
births, 22 of which were premature. There were four neonatal infections nancy. In addition, of all the myeloproliferative neoplasms, ET has the
and two congenital malformations. 118 highest proportion of affected females of child-bearing age. One study

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