PMID- 33533561
OWN - NLM
STAT- MEDLINE
DCOM- 20211014
LR  - 20211014
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Linking)
VI  - 68
IP  - 5
DP  - 2021 May
TI  - Hematopoietic stem cell transplantation for mitochondrial neurogastrointestinal 
      encephalopathy: A single-center experience underscoring the multiple factors 
      involved in the prognosis.
PG  - e28926
LID - 10.1002/pbc.28926 [doi]
AB  - BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a 
      progressive autosomal recessive disorder characterized by cachexia, 
      gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy, and brain 
      magnetic resonance imaging (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 
      mitochondrial DNA (mtDNA) instability. Death is mainly due to GI complications: 
      intestinal perforation, peritonitis, and/or liver failure. Based on our previous 
      observations in three patients with MNGIE that platelet infusions resulted in a 
      transient 40% reduction of plasma nucleoside levels, in 2005 we performed the 
      first hematopoietic stem cell transplantation (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 human leukocyte antigen (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 two patients. Fifteen years post HSCT, 
      the first transplanted patient is seemingly cured. Severe GI symptoms before 
      transplantation were mostly irreversible and were poor prognostic factors. 
      CONCLUSIONS: Allogenic HSCT could constitute a curative therapeutic option for 
      carefully selected, young, presymptomatic, 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.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Zaidman, Irina
AU  - Zaidman I
AUID- ORCID: 0000-0002-7549-0935
AD  - Department of Bone Marrow Transplantation and Cancer Immunotherapy, 
      Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
FAU - Elhasid, Ronit
AU  - Elhasid R
AUID- ORCID: 0000-0002-5663-6919
AD  - Department of Hematology-Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, 
      Israel.
FAU - Gefen, Aharon
AU  - Gefen A
AD  - Division of Pediatric Hematology Oncology and Bone Marrow Transplantation, Ruth 
      Rappaport Children's Hospital, Rambam Medical Center, Haifa, Israel.
FAU - Yahav Dovrat, Anat
AU  - Yahav Dovrat A
AD  - Department of Radiology, Rambam Health Care Campus, Haifa, Israel.
FAU - Mutaz, Sultan
AU  - Mutaz S
AD  - Department of Pediatrics, Makassed Hospital, Faculty of Medicine, Al-Quds 
      University, Jerusalem, Israel.
FAU - Shaoul, Ron
AU  - Shaoul R
AUID- ORCID: 0000-0001-5667-8759
AD  - Gastroenterology institute, Ruth Rappaport Children's Hospital, Rambam Medical 
      Center, Haifa, Israel.
AD  - Technion Faculty of Medicine, Haifa, Israel.
FAU - Eshach Adiv, Orly
AU  - Eshach Adiv O
AD  - Technion Faculty of Medicine, Haifa, Israel.
AD  - Pediatric Gastroenterology and Nutrition Unit, "HyllelYaffe" Medical Center, 
      Hadera, Israel.
FAU - Mandel, Hanna
AU  - Mandel H
AD  - Technion Faculty of Medicine, Haifa, Israel.
AD  - Metabolic Clinic, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, 
      Haifa, Israel.
FAU - Tal, Galit
AU  - Tal G
AD  - Metabolic Clinic, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, 
      Haifa, Israel.
AD  - Pediatric B Department, Ruth Rappaport Children's Hospital, Rambam Health Care 
      Campus, Haifa, Israel.
LA  - eng
PT  - Journal Article
DEP - 20210203
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - Visceral myopathy familial external ophthalmoplegia
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Cohort Studies
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Intestinal Pseudo-Obstruction/*therapy
MH  - Male
MH  - Muscular Dystrophy, Oculopharyngeal/*therapy
MH  - Ophthalmoplegia/*congenital/therapy
MH  - Pedigree
MH  - Prognosis
MH  - Retrospective Studies
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - hematopoietic stem cell transplantation
OT  - mitochondrial neurogastrointestinal encephalopathy
EDAT- 2021/02/04 06:00
MHDA- 2021/10/15 06:00
CRDT- 2021/02/03 08:39
PHST- 2020/12/21 00:00 [revised]
PHST- 2020/09/28 00:00 [received]
PHST- 2021/01/12 00:00 [accepted]
PHST- 2021/02/04 06:00 [pubmed]
PHST- 2021/10/15 06:00 [medline]
PHST- 2021/02/03 08:39 [entrez]
AID - 10.1002/pbc.28926 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2021 May;68(5):e28926. doi: 10.1002/pbc.28926. Epub 2021 
      Feb 3.