Issues of imatinib and pregnancy outcome.
The introduction of tyrosine kinase inhibitors into clinical practice now offers most patients with chronic myelogenous leukemia lengthy remissions and the possibility of normal life expectancies. These improved survivals have resulted in the need to address issues relating to quality of life, including fertility and procreation. Treatment may require lifelong daily therapy with drugs that might inhibit proteins essential to gonadal function, implantation, and embryogenesis. Animal data suggest that imatinib at standard dosages is unlikely to impair fertility in either adult male or female animals. However, human data remain limited, particularly in children and adolescents. Children born to men who are actively taking imatinib at conception seem healthy, and current advice is not to discontinue treatment. In contrast, data are less encouraging for children born to women exposed to imatinib during pregnancy. Although numbers are small, a disturbing cluster of rare congenital malformations has prevented imatinib from being recommended safely, particularly during the period of organogenesis. Alternative strategies for managing pregnancy in chronic myelogenous leukemia include one or both of regular leukapheresis and interferon-alpha. Pregnancy in advanced-phase disease presents particular problems.
Apperley
Jane
J
Imperial College, Hammersmith Campus, London, England W12 0NN. j.apperley@imperial.ac.uk
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001549:Benzamides; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D023421:Models, Animal; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D011788:Quality of Life; D012307:Risk Factors; D013723:Teratogens / Q000633:toxicity
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013723:Teratogens; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases