mercaptopurine and Diseases-in-Twins

A 29-year-old pregnant woman diagnosed with acute lymphocytic leukemia maintained remission with daily cyclophosphamide and intermittent prednisone treatment. She delivered a male twin with multiple congenital abnormalities who was diagnosed with papillary thyroid cancer at 11 years of age and stage III neuroblastoma at 14 years of age. The female twin was unaffected and has exhibited normal development to date. First trimester exposure to cyclophosphamide has been associated with major malformations. Metabolites of cyclophosphamide have been demonstrated to be teratogens and carcinogens in animals. Differences in placental or fetal hepatic cytochrome P-450 may account for the variability in response between the twins. In addition, disparity between the twins may be the result of differences in metabolite inactivating enzymes present either in fetal liver or placenta. The risk of second malignancies caused by alkylating agents such as cyclophosphamide has been well documented in adults and children but to the best of our knowledge this is the first description of transplacental second cancer.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adrenal Gland Neoplasms; Adult; Aminopterin; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Papillary; Cyclophosphamide; Diseases in Twins; Female; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Mercaptopurine; Neuroblastoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Pregnancy; Pregnancy Complications, Neoplastic; Prenatal Exposure Delayed Effects; Thyroid Neoplasms; Time Factors; Twins, Dizygotic; Vincristine

A subacute myelomonocytic leukemia was diagnosed in 28-month-old cotwins. At this age, their spontaneously dividing cells had a normal karyotype. A few months later, after treatment with 6-mercaptopurine, the following karyotypes were observed: 50,XX, +X, +13, +19, +21 in one and 51,XX, +X, +X, +10, +19, +21 in the other. After bone marrow transplantation, both relapsed although they had received high doses of chemo- and radiotherapy. One developed a clone 46,XX,del(20q), which acquired other clonal rearrangements. The other child developed two different abnormal clones, both with unbalanced rearrangement of chromosome 13. Some of these clones may correspond to immature erythroblasts. The gain of chromosomes, especially for #13, which occurred independently in the cotwins by various mechanisms and at different periods during the disease, is very striking. It may indicate the existence of a strong selective advantage for trisomic 13 cells and may be related to the genetic constitution of the patients.

Topics: Bone Marrow Transplantation; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 13; Diseases in Twins; Female; Humans; Infant; Karyotyping; Leukemia, Myelomonocytic, Acute; Mercaptopurine; Twins; Twins, Monozygotic