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 posttransplant; 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 intestinal lung disease observed in dyskeratosis congenita patients following marrow transplantation is not understood.
Langston
A A
AA
Fred Hutchinson Cancer Research Center, Seattle, Washington 98118, USA.
Sanders
J E
JE
Deeg
H J
HJ
Crawford
S W
SW
Anasetti
C
C
Sullivan
K M
KM
Flowers
M E
ME
Storb
R
R
D000328:Adult; D000741:Anemia, Aplastic / Q000150:complications / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007642:Keratosis / Q000150:complications* / Q000151:congenital; D008171:Lung Diseases / Q000209:etiology; D008297:Male; D009260:Nail Diseases / Q000150:complications / Q000151:congenital; D009894:Opportunistic Infections / Q000150:complications; D014184:Transplantation, Homologous; D016896:Treatment Outcome