Abstract
Dyskeratosis congenita (DC) is characterized by reticular skin pigmentation, oral leukoplakia and abnormal nails. Patients with DC have very short telomeres and approximately one-half have mutations in telomere biology genes. A majority of patients with DC develop BM failure (BMF). Hematopoietic cell transplantation (HCT) represents the only known cure for BMF in DC, but poses significant toxicities. We report six patients who underwent allogeneic HCT with a novel nonmyeloablative conditioning regimen specifically designed for DC patients. Graft sources included related PBSCs (1), unrelated BM (2) and unrelated double umbilical cord blood (3). Complete donor engraftment was achieved in five of six patients. One patient had initial autologous hematopoietic recovery, which was followed by a second transplant that resulted in 88% donor chimerism. With a median follow-up of 26.5 months, four patients are alive, three of whom were recipients of unrelated grafts. We conclude with this small study that encouraging short-term survival can be achieved with HCT in patients with DC using a preparative regimen designed to promote donor engraftment and minimize life-threatening disease-specific complications such as pulmonary fibrosis. Long-term follow-up will be crucial with respect to individualized patient care with each of the transplanted individuals.
Trial registration:
ClinicalTrials.gov NCT00455312.
Publication types
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Clinical Trial
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Alemtuzumab
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm / administration & dosage
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Antibodies, Neoplasm / adverse effects
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Antibodies, Neoplasm / therapeutic use
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Bone Marrow Transplantation / adverse effects
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Child, Preschool
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Combined Modality Therapy / adverse effects
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Cord Blood Stem Cell Transplantation / adverse effects
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / adverse effects
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Cyclophosphamide / therapeutic use
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Dyskeratosis Congenita / physiopathology
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Dyskeratosis Congenita / therapy*
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Female
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Hematopoietic Stem Cell Transplantation* / adverse effects
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Humans
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Male
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Peripheral Blood Stem Cell Transplantation / adverse effects
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Pulmonary Fibrosis / etiology
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Pulmonary Fibrosis / prevention & control
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Transplantation Conditioning / adverse effects
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Transplantation Conditioning / methods*
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Vidarabine / administration & dosage
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Vidarabine / adverse effects
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Vidarabine / analogs & derivatives
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Vidarabine / therapeutic use
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Whole-Body Irradiation / adverse effects
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Young Adult
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm
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Antineoplastic Agents
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Alemtuzumab
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Cyclophosphamide
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Vidarabine
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fludarabine
Associated data
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ClinicalTrials.gov/NCT00455312