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Current Studies at Motherisk
Neurodevelopment of Children Exposed in-Utero to Chemotherapy for Maternal Breast Cancer (Dr. I Nulman)
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Cancer in Pregnancy: Busulfan
Busulfan (Myleran) is an alkylating antineoplastic agent with particular toxicity for the bone marrow.
|In vitro studies||Embryonic cells||DNA inhibition synthesis 1|
|Animal studies *||rats||single dose||limb deformities, radial/tibial ray 2|
|18-34 mg/kg on 12th day||cleft palate, stunting and digital defects 3|
|10 mg/kg on gestation day 12 or 13 or later||germ cells depletion, ovarian dysgenesis, destruction of seminiferous tubules 4,5|
|Human studies||Epidemiological studies||No epidemiological studies of congenital anomalies among the infants of women treated with busulfan during pregnancy.|
|Case reports||1st trim exposure||Twenty-two case reports of first trimester exposure were located. The following malformed children were reported:
1. An abortus with myeloschisis 6
2. An abortus with unspecified defects 7
|busulfan + 6-MP||3. A baby with cleft palate, stunted growth, corneal opacity and microphtalmia, external genitalia poorly developed, death with 10 days8
4. A baby with pyloric stenosis 9
5. A baby with an anomalous left hepatic lobe 9
|2nd and 3rd trim||There are more than 20 cases with normal outcome with 2nd or 3rd trim exposures to busulfan.
A case report of a baby with kidney agenesis, hydronephrosis, liver calcification but the exposure in this case was after 20 weeks of pregnancy thus making it difficult to establish a cause - effect relationship. This baby had also intrauterine growth retardation which was attributed to the busulfan exposure 10.
A few infants with prenatal exposure to busulfan have been followed for periods of up to 10 years with respect of growth and mental development, without evidence of adverse outcome 11.
Obs: Busulfan therapy has been associated with chromosomal damage, but the clinical significance of this to the fetus is unknown 12.
- Anuszewska E. Effects of busulfan on embryonic cells in vitro. PolJ Pharmacol Pharm; 43: 129-33, 1991 (English abstract).
- Kato et al: Experimental study of radial ray deficiency. JHand Surg 15: 470-6, 1990.
- Murphy et al: The comparative effects of polyfunctional alkylating agents in the rat fetus with additional notes on the chicken embryo. Ann N Y Acad Sci 68: 762-81, 1958.
- Heller and Jones: Production of ovarian dysgenesis in the rat and human by busulfan. Am J Obstet Gynecol 89:414-20, 1964.
- Pelloux et al: Effects of busulfan on ovarian folliculogenesis, steroidogenesis and anti-mullerian activity of rat neonates. ActaEndocrinol (Copenh) 118: 218-26, 1988.
- Abramovici et al: Myeloschisis in a six weeks embryo of a leukemia woman treated by busulfan. Teratology 18: 241-6, 1978.
- De Rezende et al: Leucemia e Gravidez. Rev Ginecol Obstet117:46, 1965.
- Diamond et al: Transplacental transmission of busulfan (Myleran)in a mother with leukemia. Pediatrics 25: 85-90, 1960.
- Nicholson: Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynecol Commonw 75:307-12, 1968.
- Boros & Reynolds: Intrauterine growth retardation following third trimester exposure to busulfan. Am J obstet Gynecol 129: 111-2,1977.
- Lee et al: Leukemia during pregnancy. Am J Obstet Gynecol 84:455-8, 1962.
- Gebhart et al: Chromosomal aberrations during busulfan therapy. Deutsche Med Wochenschr 99: 52-6, 1974.