title: Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.
abstract: The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.
authors: Hematology, University Hospital Basel, Basel, Switzerland.
authors: M
authors: M
authors: Medinger
authors: GMP Facility, University Hospital Basel, Basel, Switzerland.
authors: W
authors: W
authors: Krenger
authors: Hematology, University Hospital Basel, Basel, Switzerland.
authors: A
authors: A
authors: Jakab
authors: Hematology, University Hospital Basel, Basel, Switzerland.
authors: J
authors: J
authors: Halter
authors: Hematology, University Hospital Basel, Basel, Switzerland.
authors: A
authors: http://orcid.org/0000-0002-7942-6746
authors: A
authors: Buser
authors: Hematology, University Hospital Basel, Basel, Switzerland.
authors: C
authors: C
authors: Bucher
authors: Hematology, University Hospital Basel, Basel, Switzerland.
authors: J
authors: J
authors: Passweg
authors: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors: A
authors: http://orcid.org/0000-0002-1100-3819
authors: A
authors: Tzankov
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D018952:Antigens, CD34 / Q000032:analysis; D019540:Area Under Curve; D015415:Biomarkers; D001853:Bone Marrow / Q000098:blood supply / Q000473:pathology* / Q000502:physiology; D002454:Cell Differentiation; D015331:Cohort Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology; D064231:Nestin / Q000032:analysis*; D011347:Procollagen / Q000032:analysis; D012372:ROC Curve; D012038:Regeneration; D055153:Stem Cell Niche; D019172:Transplantation Conditioning / Q000009:adverse effects
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C577484:NES protein, human; D064231:Nestin; D011347:Procollagen