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

Dyskeratosis Congenita research study

What is the primary objective of this study?

Dyskeratosis congenita is a disease that affects numerous parts of the body, most typically causing failure of the blood system. Lung disease, liver disease and cancer are other frequent causes of illness and death. Bone marrow transplantation (BMT) can cure the blood system but can make the lung and liver disease and risk of cancer worse, because of DNA damaging 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 DNA damaging agents in patients with DC, and still have a successful BMT. In this protocol we will test whether a regimen that avoids DNA alkylators and radiation can permit successful BMT without compromising survival in patients with DC.

Who is eligible to participate?

Inclusion Criteria: - 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, or ACD 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 Exclusion Criteria: - Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination. - 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. - Prior solid organ transplantation

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Dyskeratosis Congenita

Hoyeraal Hreidarsson Syndrome

Revesz Syndrome

Aplastic Anemia

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Biological:alemtuzumabConditioning: alemtuzumab 0.2 mg/kg/dose IV x 5 doses

Drug:Fludarabinefludarabine 30 mg/m2/dose IV x 6 doses


Drug:Mycophenolate mofetil

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

alemtuzumab/fludarabine conditioningalemtuzumab/fludarabine conditioning; cyclosporins/mycophenolate mofetil GVHD prophylaxis

Study Status


Start Date: July 2012

Completed Date: December 2034

Phase: Phase 2

Type: Interventional


Primary Outcome: Primary engraftment

Secondary Outcome: Survival to day+100 post-BMT

Study sponsors, principal investigator, and references

Principal Investigator: Suneet Agarwal, MD, PHD

Lead Sponsor: Boston Children’s Hospital

Collaborator: Dana-Farber Cancer Institute

More information:

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