Aplastic anemia (AA) is a serious hematological disorder characterized by pancytopenia and defective bone marrow (BM) microenvironment. Previous investigations have demonstrated that there is a defect of angiogenesis in the BM of patients with AA. However, whether abnormalities of the BM microenvironment, particularly the overall specialization of niches, which have been classified into osteoblastic, vascular, and perivascular niches, are involved in the pathogenesis of AA is unknown. In the present study, 46 patients with AA and 15 controls were selected. The cellular elements of the BM microenvironment, including endosteal, vascular, and perivascular cells, were analyzed by immunohistochemical staining in situ. Patients with AA showed markedly fewer endosteal cells [0.33 vs 3.67 per high-power field (hpf); P < 0.05], vascular cells (8.00 vs 12.67 per hpf; P < 0.05), and perivascular cells (7.17 vs 10.67 per hpf; P < 0.05) compared with controls. These data indicate that AA is associated with impaired hematopoietic stem cell niches.
Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells. However, no significant differences in endosteal cells were detected. We explored the cause of this restoration by analyzing the origin of BM mesenchymal stem cells (BM-MSCs) and the expression of cytokines in BM plasma. STR-PCR revealed that the BM-MSCs were derived from the host, not the donor. In addition, significantly elevated levels of vascular endothelial growth factor (VEGF) were found after allo-HSCT. Our data indicates that vascular and perivascular niches are numerically restored, but the endosteal niche remains numerically impaired in patients with AA after allo-HSCT, and that levels of VEGF, but not donor-derived BM-MSCs, may correlate with the restoration of BM niches.
To assess the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) patients with infection, we conducted a retrospective study on 65 SAA patients with infection who received allo-HSCT from August 2012 to December 2016. All patients received antibacterial and/or antifungal therapy before transplantation. The infection status after initial anti-infection therapy was classified as complete response (CR) (n = 14) or partial response/stable disease (PR/SD) (n = 51) before transplantation. The median times for myeloid engraftment in the PR/SD and CR groups were 10.5 days (range, 7 to 22) and 10 days (range, 8 to 11), with cumulative incidences of 98% and 100%, respectively. With a median follow-up of 788 days (range, 181 to 1758), patients with PR/SD had comparable results for 3-year estimated overall survival (85.4% versus 92.9%, P = .530) and 3-year failure-free survival (82.7% versus 92.9%, P = .458) with 14 patients with CR who received contemporaneous transplantation. In multivariate analysis, poor survival outcomes for the entire cohort was significantly associated with poor pretransplantation performance status. This retrospective study indicated that allo-HSCT may be a feasible therapeutic option for SAA patients with infection.
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