Cancer chemotherapeutic agents as human teratogens

Selig, Brady P.; Furr, J. R.; Huey, Ryan; Moran, Colin Neil; Alluri, Vinod N.; Medders, Gregory R.; Mumm, Christina D.; Hallford, Henry Gene; Mulvihill, John J.

doi:10.1002/bdra.23063

Cited by 34 publications

(27 citation statements)

References 352 publications

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“…27 Corticosteroids were not highly teratogenic in a prospective study by Koren and Lishner of 184 women exposed during pregnancy. 22 L-asparaginase derived from Escherichia coli or Erwinia chrysanthemi significantly reduces the level of coagulation Congenital anomalies, especially of kidneys, gut, brain, heart, skeleton.…”

Section: 28mentioning

confidence: 94%

“…2,27,29,30 The risk of L-asparaginase-induced coagulopathy in childhood ALL increases with age and is highest in adolescents; 31 this risk may be expected to be exacerbated during pregnancy, which itself is a hypercoagulable state, but only limited data from animal studies are available. L-asparaginase during the first trimester was shown in preclinical studies to produce congenital malformations in 17% of viable fetuses and resorption of 57% of implanted embryos.…”

Section: Aviles and Nizmentioning

confidence: 99%

“…The documented malformation rate is no more than 10% after first-trimester exposure, 27 as vinca alkaloids-with their high affinity for protein binding-cross the placenta poorly.…”

mentioning

confidence: 99%

“…67 Cyclophosphamide has been studied in 209 cases, with a 26% rate of adverse pregnancy outcomes overall and a 22% rate of fetal malformation after first-trimester exposure. 27 However, most reported cases have involved combination chemotherapy, and several studies have documented safe maternal and fetal outcomes after standard cyclophosphamide-containing regimens for aggressive lymphomas during pregnancy. 2,4,13,19,20 Cytarabine exposure during the first trimester has been found to pose an 11% risk of congenital anomalies, 27 while second-and third-trimester exposure is associated with increased risk of prematurity, low birth weight, and possibly intrauterine fetal demise.…”

mentioning

confidence: 99%

“…27 However, most reported cases have involved combination chemotherapy, and several studies have documented safe maternal and fetal outcomes after standard cyclophosphamide-containing regimens for aggressive lymphomas during pregnancy. 2,4,13,19,20 Cytarabine exposure during the first trimester has been found to pose an 11% risk of congenital anomalies, 27 while second-and third-trimester exposure is associated with increased risk of prematurity, low birth weight, and possibly intrauterine fetal demise. 12,26 Imatinib, the prototype tyrosine kinase inhibitor, has been teratogenic in animal studies.…”

mentioning

confidence: 99%

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Management of Concurrent Pregnancy and Acute Lymphoblastic Malignancy in Teenaged Patients: Two Illustrative Cases and Review of the Literature

Zaidi

Johnson

Church

et al. 2014

Journal of Adolescent and Young Adult Oncology

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The usual age range of acute lymphoblastic malignancies (acute lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma) includes teenagers and young adults (<22 years of age) and coincides with the age of fertility. Concurrence of acute lymphoblastic malignancy with pregnancy is therefore most likely to happen during the younger childbearing ages. However, the therapeutic challenges posed by the dual diagnosis of lymphoblastic malignancy and pregnancy have not specifically been studied in the context of age, and management guidelines for pregnant young patients are lacking. Inconsistency in defining the legal decision-making rights of pregnant teenaged patients adds a further level of complexity in this age group. Management of this challenging combination in the young patient therefore entails unique ethical considerations. Here we present two illustrative cases of teenage pregnancy complicated by acute lymphoblastic malignancy, review the available literature, and offer suggestions for the therapeutic management of such cases in adolescent and young adult patients. Importantly, practical management recommendations are provided in the context of clinical ethics principles that are universally applicable, including in developing countries, where the highest incidence of adolescent pregnancies has been documented.

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Section: 28mentioning

confidence: 94%

Section: Aviles and Nizmentioning

confidence: 99%

“…The documented malformation rate is no more than 10% after first-trimester exposure, 27 as vinca alkaloids-with their high affinity for protein binding-cross the placenta poorly.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Management of Concurrent Pregnancy and Acute Lymphoblastic Malignancy in Teenaged Patients: Two Illustrative Cases and Review of the Literature

Zaidi

Johnson

Church

et al. 2014

Journal of Adolescent and Young Adult Oncology

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Sonic Hedgehog, VACTERL, and Fanconi anemia: Pathogenetic connections and therapeutic implications

Lubinsky

2015

American J of Med Genetics Pt A

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Three systems with VACTERL association findings- mutations of the Sonic Hedgehog (SHH) signaling pathway in mice, murine adriamycin teratogenicity, and human Fanconi anemia (FA) pathway mutations, may all involve a similar mechanism. SHH is up-regulated in irradiated cells, and DNA breaks common with radiation damage in the adriamycin and FA systems are plausible signals for such effects, which would affect development. Since FA related DNA breakage occurs throughout life, SHH disturbances may account for later FA related findings involving hematopoietic and malignancy issues. In support, androgen, a standard treatment for FA hematologic failure, down-regulates SHH, and common FA malignancies such as squamous cell carcinomas and acute myeloid leukemia have been linked to enhanced SHH function. This suggests that interventions lowering SHH levels may be useful therapeutically. Also supporting a connection between pre- and post- natal findings, the frequency and number of VACTERL anomalies with FA correlate with the severity and onset of hematopoietic and malignancy issues. In FA, radial anomalies are the most common of these defects, followed by renal findings, while vertebral and gastrointestinal anomalies are relatively uncommon, a pattern that differs from observations of the VACTERL association. Genes with more severe effects also show a greatly increased incidence of brain abnormalities, and a paucity of such findings with other FA genes suggests that brain development is relatively refractory to SHH related effects, accounting for the rarity of such findings with the association.

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Species Differences in Renal Development and Associated Developmental Nephrotoxicity

Frazier

2017

Birth Defects Research

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The developing kidney is sensitive to both morphological and functional disturbances during the gestational and postnatal phases of growth and differentiation. Exposure to drugs or chemicals during these critical windows of renal development can result in aplasia, dysplasia, polycystic kidney disease, hydronephrosis, or other features characteristic of nephrotoxicity, including tubule dilation, necrosis, or mineralization. Functional effects can occur without associated morphological abnormalities. Differences in the timing of nephrogenesis and morphologic renal development among species help to explain specific phenotypes of various gestational and postnatal teratogens and nephrotoxins. Functional maturation follows anatomical maturation, but important differences in maximally achieved glomerular filtration rate, concentrating ability and acid-base equilibrium between species makes comparison of these timings critical for accurate and consistent translation of laboratory animal toxicity data to the human clinical experience. Species and age dependent differences in the maturation of kidney transporters, renal xenobiotic metabolism and renal blood flow can have a profound effect on the toxicity profiles of agents and marked differences in the tolerability based on age. Advances in the understanding of the genetics of inherited renal diseases and the underlying cellular and molecular pathogenesis of renal developmental anomalies has helped provide mechanistic understanding of many teratogenic and perinatal nephrotoxic agents. Investigative studies have provided important translational and mechanistic information for assessing human pediatric nephrotoxic potential. Birth Defects Research 109:1243-1256, 2017. © 2017 Wiley Periodicals, Inc.

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Cancer chemotherapeutic agents as human teratogens

Abstract: Systematic ascertainment of women early in pregnancy, preferably in a population base, is needed for assessment of true risks. Long-term follow-up is needed to rule out neurobehavioral effects.

Cited by 34 publications

References 352 publications

Management of Concurrent Pregnancy and Acute Lymphoblastic Malignancy in Teenaged Patients: Two Illustrative Cases and Review of the Literature

Management of Concurrent Pregnancy and Acute Lymphoblastic Malignancy in Teenaged Patients: Two Illustrative Cases and Review of the Literature

Sonic Hedgehog, VACTERL, and Fanconi anemia: Pathogenetic connections and therapeutic implications

Species Differences in Renal Development and Associated Developmental Nephrotoxicity

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