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Successful pregnancies after bone marrow transplantation for Fanconi anemia

Bone Marrow Transplantation volume 34, pages 1099–1100 (2004)Cite this article

Fanconi anemia (FA) is a rare autosomal recessive chromosome instability syndrome characterized by progressive bone marrow (BM) failure, skeletal defects, reduced fertility and increased susceptibility to malignancy. Endocrinopathies are a common feature of FA and pregnancy is uncommon.1 FA cells of all organ tissues are hypersensitive to DNA crosslinking agents and to oxygen and have cell cycle abnormalities. Hematopoietic stem cell transplantation (HSCT), using an adapted attenuated conditioning regimen, represents the only curative therapy capable of restoring normal hematopoiesis in patients with FA. Nevertheless, HSCT only cures hematopoietic disorder of FA and does not change the instability syndrome outside the BM.

A 17-year-old girl was diagnosed with FA following identification of pancytopenia. Initial CBC was: hemoglobin 6.8 g/dl (reticulocytes 34 × 109/l), platelets 31 × 109/l and WBC 4.3 × 109/l (neutrophils: 1.7; lymphocytes: 2.3). The BM biopsy showed severe medullary hypoplasia. The chromosome breakage test using mitomycin was positive for FA with a greater than 12-fold patient/control ratio. Past medical history was unremarkable. Menarche occurred at age 11 followed by regular menstrual cycles. Physical examination disclosed no stigmata of FA. At 3 months following diagnosis, she was transplanted with an HLA-matched sibling BM. The conditioning regimen contained cyclophosphamide (20 mg/kg total dose, over 4 days), thoraco-abdominal irradiation (500 cGy) and antithymoglobulin (Atgam, Pharmacia & Upjohn; 60 mg/kg total dose, over 4 days). GVHD prophylaxis consisted of cyclosporin A and short-course methotrexate. Engraftment was observed on day +19. She has had stable ⩾90% donor chimerism, with normal CBC. The patient had received various combinations of estrogens and progestagens since the age of 17 for birth control, but experienced mood swings and weight gain. Secondary amenorrhea, associated with hot flushes, dyspareunia and a decrease in breast volume, was diagnosed 18 months after transplantation, following cessation of her contraception. Hormonal dosages were: estradiol <50 pmol/l (N>110–183), FSH: 97.4UI/l (N<15 in luteal phase) and LH: 53UI/l (N<20 in luteal phase). Thyroid function tests were normal (TSH: 1.9 mU/l). She had no evidence of other endocrine disorders. In total, 30 months after transplantation, the gynecological status remained unchanged and was considered permanent. The patient was referred for oocyte donation but presented with an unstimulated pregnancy. In total, 52 months after transplantation, she delivered a 4030 g normal male at 39.5 weeks gestation. The patient has since had a second pregnancy ending with the birth of a normal female baby at +66 months following transplant (weight=4050 g).

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Authors and Affiliations

  1. Service d'Hématologie et Oncologie Pédiatrique, Hôpital Sainte Justine, 3175 Côte Sainte Catherine, Montréal, H3T 1C5, Québec, Canada

    J H Dalle, M Duval, P Rousseau, J Champagne, M F Vachon & M A Champagne

  2. Service d'Endocrinologie Pédiatrique, Hôpital Sainte Justine, Montréal, Québec, Canada

    C Huot

  3. Service de gynécologie et obstétrique, Hôpital Sainte Justine, Montréal, Québec, Canada

    D Francoeur

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  1. J H Dalle
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Dalle, J., Huot, C., Duval, M. et al. Successful pregnancies after bone marrow transplantation for Fanconi anemia. Bone Marrow Transplant 34, 1099–1100 (2004). https://doi.org/10.1038/sj.bmt.1704680

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