Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita

Ki vehet részt

• Bone marrow hypocellular for age
• Moderate or severe aplastic anemia defined by one of the following: peripheral blood neutrophils < 0.5 x 10\^9/L; platelets < 30 x 10\^9/L or platelet transfusion dependence; reticulocytes < 50 x 10\^9/L in anemic patients or red cell transfusion dependence
• Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence of two or more associated features; OR a pathogenic mutation in DKC1,TERC, TERT, NOP10, NHP2, TCAB1, TINF2, CTC1, PARN, RTEL1, ACD, NAF1, STN1, or ZCCHC8, as reported by a CLIA-approved laboratory; OR age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes as reported by a CLIA-approved laboratory; OR Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome
• Availability of a related or unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C, and DRB1
• Patient and/or legal guardian must be able to sign informed consent
• Donor must provide a marrow allograft
• Diagnosis of Fanconi anemia must be excluded by mitomycin C or diepoxybutane chromosomal breakage testing on peripheral blood at a CLIA-approved laboratory (not required for patients with a genetic mutation consistent with DC)
• Adequate renal function with glomerular filtration rate equal to or greater than 30 ml/min/1.73 m2

Ki nem vehet részt

• Positive patient anti-donor HLA antibody, which is deemed clinically significant
• Prior allogeneic marrow or stem cell transplantation
• Prior solid organ transplantation
• Uncontrolled bacterial, viral or fungal infections
• Positive test for the human immunodeficiency virus (HIV)
• Known severe or life-threatening allergy or intolerance to fludarabine, alemtuzumab, mycophenolate mofetil or both cyclosporine and tacrolimus
• Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination
• Karnofsky/Lansky performance status < 40
• Pregnancy or breastfeeding