Non-TBI and Alkylator-free Conditioning for Allogeneic Bone Marrow Transplantation for Bone Marrow Failure Due to Dyskeratosis Congenita / Telomere Disease
Dyskeratosis congenita (DC) is an inherited multisystem disorder, which classically presents
with a clinical triad of skin pigment abnormalities, nail dystrophy, and oral leukoplakia.
DC is part of a spectrum of telomere biology disorders, which include some forms of
inherited idiopathic aplastic anemia, myelodysplastic syndrome, and pulmonary fibrosis and
the congenital diseases Hoyeraal-Hreidarsson syndrome and Revesz syndrome. Progressive bone
marrow failure (BMF) occurs in more than 80% of patients under 30 years of age and is the
primary cause of morbidity and mortality, followed by pulmonary failure and malignancies.
Allogeneic hematopoietic cell transplantation (HCT) is curative for the hematological
defects, but several studies have demonstrated poor outcomes in DC patients due to increased
early and late complications. A predisposition to pulmonary failure, vascular disease and
secondary malignancies may contribute to the high incidence of fatal complications following
HCT in DC patients, and provides an impetus to reduce exposure to chemotherapy and
radiotherapy in preparative regimens. Recent studies suggest that fludarabine-based
conditioning regimens provide stable engraftment and may avoid the toxicities seen after HCT
for DC, but studies to date are limited to case reports, retrospective studies and a single
prospective trial. In this study, we propose to prospectively evaluate the efficacy of a
fludarabine- and antibody-based conditioning regimen in HCT for DC patients, with the goals
of maintaining donor hematopoiesis and transfusion independence while decreasing early and
late complications of HCT for DC.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Day +100 Post-transplant Survival
To determine feasibility, in terms of the proportion of patients who survive to Day+100 post-transplant, of a reduced intensity conditioning regimen in allogeneic HCT for BMF due to DC.
100 days post bone marrow infusion
Suneet Agarwal, MD, PHD
Boston Children's Hospital
United States: Institutional Review Board
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