Allogeneic marrow transplantation for aplastic anaemia associated with dyskeratosis congenita

Eight patients with aplastic anaemia associated with dyskeratosis congenita received allogeneic marrow grafts from either HLA-identical siblings (six patients) or HLA-matched unrelated donors (two patients), Patients who received marrow from HLA-identical siblings were conditioned with cyclophosphamide (140-200 mg/kg), with or without antithymocyte globulin. Patients who received unrelated donor marrow were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (1200 cGy). The six patients who survived for >2 weeks following transplant all had haematological evidence of engraftment, and all three patients who survived for at least a year following transplant recovered normal haematological function. Three patients died with respiratory failure and pulmonary fibrosis at 70 d, 8 years and 20 years post-transplant; three patients died during the neutropenic period of invasive fungal infections: one patient died on day 44 of refractory acute graft-versus-host disease: and one patient remains alive 463 d following transplant. The surviving patient recently underwent surgical resection of a Dukes' stage C rectal carcinoma diagnosed 14 months posttransplant. The aplastic anaemia associated with dyskeratosis congenita can be successfully treated by allogeneic bone marrow transplantation: however, this approach does not reverse the other systemic manifestations of the syndrome, The pathogenesis of the interstitial lung disease observed in dyskeratosis congenita patients following marrow transplantation is not understood.