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 factor
support

- 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 of
decompensated 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 on
biopsy

- 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