Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

OBJECTIVES:

Primary

- Estimate the incidence of detectable donor-derived collagen type VII at day 100 in
patients with epidermolysis bullosa by donor.

Secondary

- Determine the incidence of transplant-related mortality at day 180

- Determine the incidence of blood chimerism at days 21, 100, 180, 365, and 730

- Determine the incidence of neutrophil recovery at day 42 and platelet recovery at day
180

- Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade
III-IV at day 100

- Determine the incidence of chronic GVHD at 1 year

- Determine the probability of survival at 1 and 2 years

- Determine the incidence of donor derived cells in the skin

- Determine resistance to blister formation OUTLINE: This is an open-label, pilot study.

- Conditioning regimen: Busulfan intravenously (IV) over 2 hours every 6 hours on days -9
to -4, fludarabine phosphate IV over 1 hour on days -5 to -3, and high-dose
cyclophosphamide IV over 1 hour on days -5 to -2.

- Stem cell transplantation on day 0.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: 30 patients

Inclusion criteria:

- Diagnosis of epidermolysis bullosa (EB)

- Documented collagen type VII deficiency by:

- Antigenic mapping (LH7.2 antibody)

- Ultrastructure analysis of anchoring fibrils

- DNA mutation analysis

- Performance status: >50% Lansky; >50% Karnofsky

- Adequate organ function

- Renal: glomerular filtration rate > 60ml/min/1.73m2 patients aged ≤ 10 years

- Hepatic: bilirubin, aspartate aminotransferase/alanine aminotransferase
(AST/ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal 4.2.3
Pulmonary: oxygen saturation >92% 4.2.4 Cardiac: left ventricular ejection
fraction > 45%.

- Healthy related hematopoietic stem cell donor available and meeting 1 of the following
criteria:

- HLA-A, B, DRB1-identical sibling bone marrow and/or umbilical cord blood donor
(first priority)

- HLA-A, B, DRB1-matched or partially matched related donor (second priority)

- Donor may be a carrier but must be unaffected by EB

- 8/8 HLA A, B, C, DRB1 allele level matched unrelated marrow donor (third
priority)

- 7/8 HLA-A, B, C, DRB1 allele level matched unrelated marrow donor or 4/6 HLA-A, B
(antigen level), DRB1 (allele level) matched unrelated cord blood donor (fourth
priority)

Exclusion criteria:

- Active infection at time of transplantation (including active infection with
Aspergillus or other mold within 30 days)

- Squamous cell carcinoma of the skin

- History of human immunodeficiency virus (HIV) infection

- Prior transplantation with donor skin