Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
Phase: Phase 2
DFCI Protocol ID: 16-294
Dyskeratosis congenita is a disease that affects numerous parts of the body, most typically causing failure of the blood system. Lung disease and a predisposition to cancer are also frequent causes of illness and death. Bone marrow transplantation (BMT) can cure the blood system but can make the lung disease and cancer predisposition worse, because of agents such as alkylators and radiation that are typically used in the procedure. Based on the biology of DC, we hypothesize that it may be possible to avoid these agents in patients with DC, and still have a successful BMT. In this protocol we will test whether a regimen that avoids alkylators and radiation can permit successful BMT without compromising survival in patients with DC.
Dana-Farber Cancer Institute, Children's Hospital Boston
Suneet Agarwal, MD, PhD,
Children's Hospital Boston
Dana-Farber Cancer Institute:
Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, email@example.com
- Bone marrow cellularity: 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
- 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 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,
- Patient and/or legal guardian must be able to sign informed consent.
- Matched unrelated donor must consent to 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
- Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow
- Karnofsky/Lansky performance status < 40%.
- Uncontrolled bacterial, viral or fungal infections.
- Positive test for the human immunodeficiency virus (HIV).
- Pregnancy or breastfeeding.
- Known severe or life-threatening allergy or intolerance to fludarabine, alemtuzumab,
cyclosporine, or mycophenolate mofetil.
- Positive patient anti-donor HLA antibody, which is deemed clinically significant.
- Prior allogeneic marrow or stem cell transplantation.