Cancer in Pregnancy: Busulfan

Busulfan (Myleran) is an alkylating antineoplastic agent with particular toxicity for the bone marrow.

	Setting	Treatment	Outcomes
In vitro studies	Embryonic cells		DNA inhibition synthesis ¹
	Species studied
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
	Study design
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.

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

Obs: Busulfan therapy has been associated with chromosomal damage, but the clinical significance of this to the fetus is unknown ¹².

References

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.

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