title: Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation.
abstract: Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the bone marrow (BM) microenvironment are involved in the pathogenesis of PGF is unclear. In the present prospective nested case-control study, 19 patients with secondary PGF, 38 matched patients with good graft function (GGF) after allo-HSCT, and 15 healthy donors (HDs) were enrolled. The cellular elements of the BM microenvironment, including endosteal cells, perivascular cells, and vascular cells, were analyzed by flow cytometry as well as hematoxylin and eosin and immunohistochemical staining in situ. The median time to occurrence of secondary PGF was 90 days post-transplantation (range, 58 to 264 days). The patients with PGF showed markedly hypocellular marrow (10% versus 45% versus 45%; P < .0001) with scattered hematopoietic cells and significantly lower CD34(+) cells (0.07% versus 0.26% versus 0.26%; P < .0001), endosteal cells (4 per high-power field [hpf] versus 16 per hpf versus 20 per hpf; P < .001), perivascular cells (0.008% versus 0.10% versus 0.12%; P < .0001), and endothelial progenitor cells (0.008% versus 0.16% versus 0.18%; P < .0001) compared with GGF allo-HSCT recipients and HDs, respectively. Multivariate analyses revealed that endothelial progenitor cells (odds ratio, 150.72; P = .001) and the underlying disease (odds ratio, 18.52; P = .007) were independent risk factors for secondary PGF. Our results suggest that the impaired BM microenvironment may contribute to the occurrence of secondary PGF post-HSCT.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Kong
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Chang
authors.forename: Ya-Zhe
authors.initials: YZ
authors.lastname: Wang
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Sun
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Yan
authors.forename: Feng-Rong
authors.initials: FR
authors.lastname: Wang
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Liu
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Liu
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: Allogeneic hematopoietic stem cell transplantation; Bone marrow; Microenvironment; Poor graft function; Secondary