Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes.
The establishment of G-CSF-primed unmanipulated haploidentical blood and marrow transplantation (The Beijing Protocol) has achieved outcomes for the treatment of acute leukemia, myelodysplastic syndrome, and severe aplastic anemia with haploidentical allografts comparable to those of human leukocyte antigen (HLA)-matched sibling donor transplantation.
Our results demonstrate that it is unlikely that G-CSF impacts on the outcome of severe aplastic anemia; nevertheless, very late events are common and eventually impact on the prognosis of these patients, irrespectively of their age at immunosuppressive therapy (NCT01163942).
We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation.
A 3-year-old girl with severe aplastic anemia (SAA) that was unresponsive to steroid, cyclosporine and filgrastim treatments received bone marrow (BM) mesenchymal stromal cells (MSC; 1.25 x 10(6)/kg), granulocyte colony-stimulating factor (G-CSF)-mobilized BM and peripheral blood stem cell grafts from her father.
G-CSF has also been applied in priming strategies designed to enhance the sensitivity of leukemia stem cells to cytotoxic agents, in protocols aimed to induce their differentiation and accompanying growth arrest and cell death, and in severe aplastic anemia and myelodysplastic syndrome (MDS) to alleviate anemia.
Granulocyte colony-stimulating factor (G-CSF) dependent hematopoiesis with monosomy 7 in a patient with severe aplastic anemia after ATG/CsA/G-CSF combined therapy.
Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor.
The gene frequencies of A(∗)02:01, A(∗)02:06, B(∗)13:01, DRB1(∗)07:01, DRB1(∗)09:01, DRB1(∗)15:01 and DQB1(∗)06:02 in SAA patients were significantly higher than in controls (all P<0.05), while the allelic frequencies of A(∗)02:07, A(∗)11:01 and B(∗)40:01 were notably lower in SAA patients than those in the controls (P = 0.001, 0.002, 0.005, respectively).
The gene frequencies of A(∗)02:01, A(∗)02:06, B(∗)13:01, DRB1(∗)07:01, DRB1(∗)09:01, DRB1(∗)15:01 and DQB1(∗)06:02 in SAA patients were significantly higher than in controls (all P<0.05), while the allelic frequencies of A(∗)02:07, A(∗)11:01 and B(∗)40:01 were notably lower in SAA patients than those in the controls (P = 0.001, 0.002, 0.005, respectively).
However, if such a donor is not available, any single-allele or multiple-allele (HLA-C, -DRB1, -DQB1) mismatched donor is acceptable as an unrelated donor for patients with severe aplastic anemia.
However, if such a donor is not available, any single-allele or multiple-allele (HLA-C, -DRB1, -DQB1) mismatched donor is acceptable as an unrelated donor for patients with severe aplastic anemia.
In conclusion, the defective Sirt1 may be correlated to the abnormal IFNγ expression in SAA patients, and activation of Sirt1 signaling may help improve the inflammatory status of SAA.
Genetic ablation or blockade of components of IL-6-STAT3-SAA signalling prevents the establishment of a pro-metastatic niche and inhibits liver metastasis.
Aberrant cytokine profiles were secreted by SAA MSCs, with increased concentrations of interleukin-6, interferon-γ, tumor necrosis factor-α, and interleukin-1β in the CM.
In CD34(+) cells, Fas expression was significantly higher in the newly diagnosed SAA group (46.59 ± 27.60%) than the remission (6.12 ± 3.35%; P < 0.01) and control (8.89 ± 7.28%; P < 0.01) groups.
Employing unbiased RNA amplification, patient-specific gene expression profiling was carried out for CD34(+) cells from patients newly diagnosed with very severe aplastic anemia (n=13), refractory anemia (n=8) and healthy controls (n=10).
The response rate in severe aplastic anemia patients with increased IFN-γ levels in the blood plasma was higher than that in severe aplastic anemia patients with decreased IFN-γ levels in the blood plasma (73.7% vs. 25.0%, p<0.05).
In AA patients, the ratio of CD(34)(+) cells in BMMNC less than 0.1% accounts for 75% (6/8) SAA patients, compared with 10.55% (2/19) in CAA (P < 0.05).