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Cancer in Pregnancy: Cytarabine

Cytarabine is an antimetabolite used in the treatment of acute leukemia and occasionally in lymphomas. It is a nucleoside analogue, which inhibits DNA synthesis.

Setting Treatment Outcomes
Species studied
Animal studies * Mice and rats 2 to 67 times the human dose Increased frequency of limb defects, particularly ectrodactyly and digital anomalies. 1-4 These effects were time and dose dependent.
10 to 93 times the human dose, late pregnancy Increased incidence of brain and kidney defects 5-8
Chicks, rats, mice, hamsters Increased incidence of skeletal defects 9-12, cleft palate 3,10,11, cerebellar hypoplasia 5,13 and retinal dysplasia 5.
Study design
Human studies Case reports 1st trim exposure Many case reports of normal babies after 1st trimester exposure were found 14-16. Two malformed infants were reported after 1st trimester exposure to cytarabine:
Combination with thioguanine A male baby born to a mother who received cytarabine and thioguanine during the whole pregnancy. He was born at 38 weeks of pregnancy, with low birth weight (2,232g). The following anomalies were found: absence of the medial two toes of both feet, absence of the distal phalange of the left thumb and of the distal and proximal phalange of the right thumb. Otherwise he was normal. Karyotype showed no abnormalities.

The same mother got pregnant again one year later with the same chemotherapy and gave birth to a female baby without anomalies. Karyotype was normal 17

Cytarabine only A male baby born to a mother who received ARA-C as a single agent during all pregnancy. The baby showed the following anomalies: bilateral microtia with atresia of the external auditory canals; right hand with lobster claw deformity and only three digits; lower limb anomalies. Karyotype was normal 18
2nd and 3rd trim exposures Chromosomal abnormalities were described in two cases after 2nd trimester exposure to ARA-C:
A patient treated from 20th week of pregnancy with thioguanine and cytarabine. A therapeutic abortion was performed at 24 weeks. No congenital abnormalities were found at autopsy but the karyotype from chorionic tissue showed a group C trisomy mosaicism 19.

A healthy girl born to a woman who received combination therapy including ARA-C for acute lymphoblastic leukemia, from 22nd week to term. Karyotype analysis showed 46 chromosomes with the presence of gaps and a ring chromosome. The clinical significance of this finding is still unknown but it may represent an risk of cancer as well as a risk of genetic damage in the next generation 20

Three cases of intrauterine death after combination therapy were reported, two in the second trimester 21,22 and one in the third 23. One baby exposed during the second trimester was born with bruising and petechia over multipleareas. The mother was treated with doxorubicin, cytarabine and thioguanine 21.

A case of severe myelosupression in an infant exposed to combined therapy during 1st, 2nd and 3rd trim 24, details below Two other cases of neutropenia and thrombocytopenia were reported 25,26

There are many case reports of normal babies born after cytarabine exposure during the second and/or third trimester 21,27-29.

Case series No epidemiological studies of congenital anomalies among infants of women that were treated with ARA-C during pregnancy were identified. The following case series were found:

1. No congenital anomalies were observed in one series among 9 children born to women treated during pregnancy with cancer chemotherapeutic regimens that included ARA-C. Five of these women were treated during the first trimester 28. Their growth, intellectual development and cytogenetic analysis were normal in ages rangingfrom 3 - 19 years at the time of the follow-up.

2. In a series of 9 patients with acute leukemia during pregnancy, 4 of them with the use of cytarabine during the first trimester, no one was born with congenital malformation24, but 2 had a subnormal birth weight. One of them had severe pancytopenia and low birth weight. The mother of this patient received combination chemotherapy (cytosine arabinoside, prednisone, 6-mercaptorurine, methotrexate andvincristine) during 1st, 2nd and 3rd trimesters.

3. In a case series of 7 pregnant patients with acute leukemia, 4 of them with combination therapy including ARA-C during the 2nd or 3rd trimester, there were 4 live births without major malformations, but 2 of them were of low birth weight. One had a mild perinatal thrombocytopenia. Their long-term follow-up (1 to 11 years) did not show any developmental abnormality 29.

* - None of the animal studies reported in this table were conducted at The Hospital for Sick Children, Toronto, or by Motherisk.


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