Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
Conditions
Keywords
Allogeneic Hematopoietic Stem Cell Transplantation, MNGIE, Stem Cell transplant
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALHematopoietic Allogeneic Stem Cells
HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).
Sponsors
Cornell University
National Institute of Neurological Disorders and Stroke (NINDS)
Michio Hirano, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| neutrophil count (cells/L) | 42 days | engraftment success |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| number of patient survival days | 100 days | is the patient al |
| chimerism percentage | 100 days | percent of donor cell chimerism at 100 days |
| micromole/l dUrd | 100 days | level of deoxyuridine |
| micromole Thd | 100 days | level of thymidine |
Outcome results
None listed