Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia

Inclusion Criteria:

• Aged 0 - 70 years

• Acceptable hematopoeitic stem cell donor

• Dyskeratosis Congenita (DC) with evidence of BM failure defined as:

• requirement for red blood cell and/or platelet transfusions or

• requirement for G-CSF or GM-CSF or erythropoietin or

• refractory cytopenias having one of the following three

• platelets <50,000/uL or transfusion dependent

• absolute neutrophil count <500/uL without hematopoietic growth factorsupport

• hemoglobin <9g/uL or transfusion dependent

• Diagnosis of DC with a triad of mucocutaneous features:

• oral leukoplakia

• nail dystrophy

• abnormal reticular skin hyperpigmentation, or

• Diagnosis of DC with one of the following:

• short telomeres (under a research study)

• mutation in telomerase holoenzyme (DKC1, TERT, TERC, NOP10, NHP2, TCAB1)

• mutation in shelterin complex (TINF2)

• mutation in telomere-capping complex (CTC1)

• Severe Aplastic Anemia (SAA) primary transplant with evidence of BM failure:

• Refractory cytopenia defined by bone marrow cellularity <50% (with < 30%residual hematopoietic cells)

• Diagnosis of SAA with refractory cytopenias having one of the following three:

• platelets <20,000/uL or transfusion dependent

• absolute neutrophil count <500/uL without hematopoietic growth factor support

• absolute reticulocyte count <20,000/uL

• Severe Aplastic Anemia (SAA) requiring a 2nd transplant

• Graft failure as defined by blood/marrow chimerism of < 5%

• Early myelodysplastic features

• With or without clonal cytogenetic abnormalities

• Adequate organ function defined as:

• cardiac: left ventricular ejection fraction ≥ 35% with no evidence ofdecompensated heart failure

• pulmonary: DLCO ≥30% predicted, no supplemental oxygen requirement

• renal: Glomerular filtration rate (GFR) ≥30% predicted

• Voluntary written consent

Exclusion Criteria:

• Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis onbiopsy

• Pregnant or lactating

• Uncontrolled infection

• Prior radiation therapy (applies to SAA patients only)

• Diagnosis of Fanconi anemia based on DEB

• Diagnosis of dyskeratosis congenita with advanced MDS or acute myeloid leukemia with >30% blasts