MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study

The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. The stem cell transplant is called AHSCT (for "allogeneic hematopoetic stem cell transplantation"). The rare disease is called MNGIE (for "Mitochondrial NeuroGastroIntestinal Encephalomyopathy"). Patients with MNGIE will be transplanted with stem cells from an individual who is human leukocyte antigen (HLA) 10/10 matched. The purpose of the transplant is the production of thymidine phosphorylase.

Patients who have been identified as having MNGIE by genetic testing and/or reduced thymidine phosphorylase levels will be considered for this study. The study team physician will evaluate the condition of the patient and determine if they are eligible. An HLA matched donor is necessary for transplantation. If a suitable donor is found the transplant process can proceed. The patient receives immunosuppressive therapy ( 1 week in the hospital) with subsequent IV transfer of stem cells from the donor. The patient remains in the hospital for approximately 1 month to monitor the transplant. The patient is required to attend research visits at days 0, 100, 6m, 18m and 24 m.

Inclusion Criteria:

• Homozygous or compound heterozygous mutations in the TYMP gene
• Plasma thymidine level >3micromole/L
• Plasma deoxyuridine >7.5 micromole/L
• 5 to 55 years of age
• Appropriate stem cell donor (HLA 10/10 matched)
• Karnofsky performance of at least 55

Exclusion Criteria:

• Severe cognitive impairment
• Severe psychiatric illness
• Moderate to severe lung disease
• Prior episode of peritonitis due to perforated diverticula
• Prior episode of intestinal pseudo-obstruction
• Moderate to severe hepatopathy
• Moderate to severe diabetes Mellitus
• Moderate to severe cardiomyopathy
• Moderate to severe nephropathy
• Pregnancy or planning to become pregnant during study
• Hypersensitivity to E.coli derived products
• HIV disease
• Positive to anti-donor HLA DP