Recent advances in treatment of aplastic anemia

Shin, Seung Hwan; Lee, Sung Eun; Lee, Jong Wook

doi:10.3904/kjim.2014.29.6.713

Cited by 20 publications

(26 citation statements)

References 95 publications

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“…Both immunosuppressive therapy and allogeneic HSCT represent definite therapies for patients with SAA [11,12,20,21]. MSD-HSCT is the preferred first-line treatment option for younger (≤50 years) SAA patients [22]. GVHD and GR, both of which are critically influenced by the composition of the (27) .075 IFD 15 (26) 16 (29) .701 CMV viremia 14 (24) 12 (22) .770…”

Section: Discussionmentioning

confidence: 99%

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

Chen

Wei

Huang

et al. 2018

Biology of Blood and Marrow Transplantation

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We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.

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Section: Discussionmentioning

confidence: 99%

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

Chen

Wei

Huang

et al. 2018

Biology of Blood and Marrow Transplantation

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“…1 For younger (⩽40 years) patients with severe AA (SAA), if they have a suitable donors, allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is the most preferred first-line treatment, [2][3][4] whereas its applications to older patients (440 years) is limited because of inferior outcomes or no advantage compared with the alternative treatment option of immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporin A. [5][6][7][8][9] Until recently, cyclophosphamide (Cy; 200 mg/kg) ± ATG had been the most widely used conditioning regimen for patients with SAA who received MSD-SCT.…”

Section: Introductionmentioning

confidence: 97%

Comparable outcomes between younger (⩽40 years) and older (>40 years) adult patients with severe aplastic anemia after HLA-matched sibling stem cell transplantation using fludarabine-based conditioning

Shin

Jeon

Yoon

et al. 2016

Bone Marrow Transplant

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Allogeneic stem cell transplantation from HLA-matched siblings (MSD-SCT) for elderly patients with severe aplastic anemia (SAA) is not a widely accepted first-line treatment. Recently, fludarabine, lower-dose cyclophosphamide and antithymocyte globulin conditioning (Flu/lower-dose Cy/ATG) with lower toxicities has been investigated. To determine whether this regimen can overcome the negative effects of age, we analyzed 117 adult patients with SAA who received MSD-SCT using Flu/lower-dose Cy/ATG, and compared outcomes between 63 younger age group (YAG; ⩽40 years) and 54 older age group (OAG; >40 years) patients. No primary graft failure was observed. Neutrophil engraftment was significantly faster in the YAG compared with the OAG (12 vs 13 days; P=0.04). The incidences of acute grade II-IV (9.5% vs 9.3% at day 100; P=0.42) and chronic GVHD (8.1% vs 9.5% at 5 years; P=0.80), secondary graft failure (20.8% vs 7.9% at 5 years; P=0.11) and transplant-related mortality (5.4% and 11.1% at 5 years; P=0.91) were not significantly different between the YAG and OAG. In addition, failure-free (73.7% vs 81.0% at 5 years; P=0.73) and overall survival rates (93.7% vs 88.9% at 5 years; P=0.20) were comparable. Our results suggest that MSD-SCT using Flu/lower-dose Cy/ATG may be a feasible first-line treatment even in older patients with SAA.

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“…In addition to first‐line standard treatment for AA, such as IST and HSCT, developing small novel molecules which could be used to correct the differentiation imbalance of AA BM‐MSCs or improve the AA BM microenvironment is of great value. Cheng et al reported that arsenic trioxide (ATO) exerts its clinical efficacy in treating AA patients by inhibiting adipogenic differentiation and facilitating osteogenic differentiation through increasing BMP4 expression, implicating its potential wide‐spread clinical application in AA therapy.…”

Section: Discussionmentioning

confidence: 99%

Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis

Liu

et al. 2018

J Cellular Molecular Medi

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Aplastic anaemia (AA) is a life‐threatening hematopoietic disorder characterized by hypoplasia and pancytopenia with increasing fat cells in the bone marrow (BM). The BM‐derived mesenchymal stem cells (MSCs) from AA are more susceptible to be induced into adipogenic differentiation compared with that from control, which may be causatively associated with the fatty BM and defective hematopoiesis of AA. Here in this study, we first demonstrated that levamisole displayed a significant suppressive effect on the in vitro adipogenic differentiation of AA BM‐MSCs. Mechanistic investigation revealed that levamisole could increase the expression of ZFP36L1 which was subsequently demonstrated to function as a negative regulator of adipogenic differentiation of AA BM‐MSCs through lentivirus‐mediated ZFP36L1 knock‐down and overexpression assay. Peroxisome proliferator‐activated receptor gamma coactivator 1 beta (PPARGC1B) whose 3′‐untranslated region bears adenine‐uridine‐rich elements was verified as a direct downstream target of ZFP36L1, and knock‐down of PPARGC1B impaired the adipogenesis of AA BM‐MSCs. Collectively, our work demonstrated that ZFP36L1‐mediated post‐transcriptional control of PPARGC1B expression underlies the suppressive effect of levamisole on the adipogenic differentiation of AA BM‐MSCs, which not only provides novel therapeutic targets for alleviating the BM fatty phenomenon of AA patients, but also lays the theoretical and experimental foundation for the clinical application of levamisole in AA therapy.

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Recent advances in treatment of aplastic anemia

Cited by 20 publications

References 95 publications

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

Comparable outcomes between younger (⩽40 years) and older (>40 years) adult patients with severe aplastic anemia after HLA-matched sibling stem cell transplantation using fludarabine-based conditioning

Levamisole suppresses adipogenesis of aplastic anaemia‐derived bone marrow mesenchymal stem cells through ZFP36L1‐PPARGC1B axis

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