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Hematopoietic Stem Cell Transplantation (HSCT) for Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE): a Single Center Experience Underscoring the Multiple Factors Involved in the Prognosis.
  • +6
  • Irina Zaidman,
  • Ronit Elhasid,
  • Aharon Gefen,
  • Anat Yahav Dovrat,
  • Sultan Mutaz,
  • Ron Shaoul,
  • Orly Eshach Adiv,
  • Hanna Mandel,
  • Galit Tal
Irina Zaidman
Hadassah Medical Center
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Ronit Elhasid
Tel Aviv Sourasky Medical Cente, affiliated to the Sackler Faculty of Medicine, Tel Aviv University
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Aharon Gefen
Rambam Health Care Campus
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Anat Yahav Dovrat
Rambam Health Care Campus
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Sultan Mutaz
Makassed Hospital
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Ron Shaoul
Rambam Health Care Campus
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Orly Eshach Adiv
Hillel Yaffe Medical Center
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Hanna Mandel
Rambam Health Care Campus
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Galit Tal
Rambam Health Care Campus
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Abstract

Background: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a progressive autosomal recessive disorder characterized by cachexia, gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy and brain MRI white matter changes. Bi-allelic TYMP mutations lead to deficient thymidine phosphorylase (TP) activity, toxic accumulation of plasma nucleosides (thymidine and deoxyuridine), nucleotide pool imbalances and mtDNA instability. Death is mainly due to GI complications: intestinal perforation, peritonitis, and/or liver failure. Based on our previous observations in 3 patients with MNGIE, that platelet infusions resulted in a transient 40% reduction of plasma nucleoside levels, in 2005 we performed the first HSCT worldwide as a life-long source of TP in a patient with MNGIE. Procedure: HSCT was performed in a total of six patients with MNGIE. The multiple factors involved in the prognosis of this cohort were analyzed and compared to the literature experience. Results: Cell source was bone marrow in five patients and peripheral stem cells in one, all from fully HLA-matched related donors, including four who were TYMP mutation carriers. Four of six (66%) survived compared to the 37% survival rate in the literature. Reduced intensity conditioning regimen contributed to secondary graft failure in 2 patients. 15 years post-HSCT the first transplanted patient is seemingly cured. Severe GI symptoms pre-transplantation were mostly irreversible and a poor prognostic factor. Conclusions: Allogenic HSCT could constitute a curative therapeutic option for carefully selected, young, pre-symptomatic or mildly affected patients. Timing, donor selection and optimal conditioning protocol are major determinants of outcome. HSCT is inadvisable in patients with advanced MNGIE disease.

Peer review status:Published

28 Sep 2020Submission Checks Completed
28 Sep 2020Assigned to Editor
28 Sep 2020Submitted to Pediatric Blood & Cancer
01 Oct 2020Reviewer(s) Assigned
29 Oct 2020Review(s) Completed, Editorial Evaluation Pending
30 Oct 2020Editorial Decision: Revise Minor
21 Dec 20201st Revision Received
21 Dec 2020Submission Checks Completed
21 Dec 2020Assigned to Editor
24 Dec 2020Reviewer(s) Assigned
12 Jan 2021Review(s) Completed, Editorial Evaluation Pending
12 Jan 2021Editorial Decision: Accept
03 Feb 2021Published in Pediatric Blood & Cancer. 10.1002/pbc.28926