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Hematology AND Aplastic anemia [keywords]
- Low Expression of Basic Fibroblastic Growth Factor in Mesenchymal Stem Cells and Bone Marrow of Children with Aplastic Anemia. [JOURNAL ARTICLE]
- Pediatr Hematol Oncol 2013 Dec 5.
Background: Our previous experiments with gene chip suggested that basic fibroblastic growth factor (FGF2) levels were lower in mesenchymal stem cell (MSC) from aplastic anemia patients. The purpose of this study was to determine the expression of FGF2 in MSC and in bone marrow of children with aplastic anemia to better understand the role of low FGF2 expression in the pathogenesis of aplastic anemia. Procedure: MSCs from the bone marrow of aplastic anemia children and control group were cultured in vitro. Growth curves of primary and passage MSC were plotted. FGF2 gene expression in MSCs was detected using quantitative real-time polymerase chain reaction (RT-PCR). FGF2 protein expression in mononuclear cells and FGF2 protein level in extracellular fluid of bone marrow were also investigated. Result: Decreased growth of MSCs from aplastic anemia children was observed after passage 8 in serial subcultivation, and FGF2 gene expression was downregulated. Within the patients' bone marrow, low FGF2 expression was validated both in mononuclear cells and in the extracellular fluid. Conclusion: Low FGF2 gene expression in MSCs and low FGF2 protein level in bone marrow of aplastic anemia may involve to pathogenesis of aplastic anemia.
- Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: Correlation with the clinico-pathological features of aplastic anemia. [Journal Article]
- Chin J Integr Med 2013 Dec; 19(12):905-12.
To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology.Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α.Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively).AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.
- Hematologic improvement with deferasirox following tandem antithymocyte globulin treatment in a transfusion-dependent patient with severe aplastic anemia. [Journal Article]
- Rinsho Ketsueki 2013 Nov; 54(11):2047-52.
A 62-year-old man with transfusion-dependent severe aplastic anemia received immunosuppressive therapy (IST) with rabbit antithymocyte globulin and cyclosporine A in April 2010. However, his transfusion dependency did not improve. As more than 100 red blood cell (RBC) transfusions had been performed, he was administered iron chelation therapy (ICT) with deferasirox (DFX) to improve iron overload starting in July 2011. Consequently, both RBC and platelet transfusion dependency gradually improved concomitant with a decrease in serum ferritin. The bone marrow (BM) biopsy findings before administration of DFX showed severe iron accumulation and strong positive immunostaining for 8-OHdG, a marker of oxidative stress due to free iron. One year after ICT, the number of BM hematopoietic cells was increased and both iron deposition and oxidative stress were decreased. These findings suggest that DFX may contribute to hematological improvement in patients with IST-refractory aplastic anemia.
- The use of a fludarabine-based conditioning regimen in patients with severe aplastic anemia - a retrospective analysis from three Indian centers. [Journal Article]
- Clin Transplant 2013 Nov; 27(6):923-9.
Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA-identical sibling or family donors. Seventy-six patients were considered "high risk" as per criteria. The graft source included peripheral blood stem cells in 109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low-risk group (n = 45) and 64.0 ± 5.6% in the high-risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long-term survival in patients undergoing HSCT for SAA.
- [Apoptosis and its mechanisms of spleen CD4⁺ CD25⁺ regulatory T cells in severe aplastic anemiamouse model]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2013 Nov; 34(11):931-5.
To explore the apoptosis and its mechanisms of spleen CD4⁺ CD25⁺ regulatory T (Treg) cells in severe aplastic anemia (SAA) mouse model induced by interferon (IFN-γ) in combination with busulphan (BU).The BALB/c female mice SAA model was induced by intraperitoneal injection with IFN-γ and intragastric administration with BU (combined group, n=16), with BU group (n=16), IFN-γ group (n=16) and normal group (n=16) as controls. Spleen Treg cells were purified by using of immunomagnetic beads. Apoptosis was detected by flow cytometry. AKt and TGF-β expression was measured by Western blot.Apoptosis of spleen Treg cells in combined group [(33.21±0.65)%] was significantly higher than that in BU group [(21.58±0.64)%], IFN-γ group [(17.62±1.05)%], and control[(27.38±1.89)%] (P<0.05). A significantly lower expression of AKt and TGF-β protein was also seen in combined group (0.30±0.05 and 0.17±0.05), as compared to the other three groups (P<0.05).Excessive apoptosis of Treg cells was found in SAA mouse model, which may be a cause of Treg cells decrease in patients with AA. The down-regulated expression of AKt and TGF-β could play a role in increased apoptosis of Treg cells. Our data may provide a new treatment strategy in AA.
- Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): An initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). [JOURNAL ARTICLE]
- Pediatr Blood Cancer 2013 Nov 27.
Randomized clinical trials in pediatric aplastic anemia (AA) are rare and data to guide standards of care are scarce.Eighteen pediatric institutions formed the North American Pediatric Aplastic Anemia Consortium to foster collaborative studies in AA. The initial goal of NAPAAC was to survey the diagnostic studies and therapies utilized in AA.Our survey indicates considerable variability among institutions in the diagnosis and treatment of AA. There were areas of general consensus, including the need for a bone marrow evaluation, cytogenetic and specific fluorescent in situ hybridization assays to establish diagnosis and exclude genetic etiologies with many institutions requiring results prior to initiation of immunosuppressive therapy (IST); uniform referral for hematopoietic stem cell transplantation as first line therapy if an HLA-identical sibling is identified; the use of first-line IST containing horse anti-thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling donor is not identified; supportive care measures; and slow taper of CSA after response. Areas of controversy included the need for telomere length results prior to IST, the time after IST initiation defining a treatment failure; use of hematopoietic growth factors; the preferred rescue therapy after failure of IST; the use of specific hemoglobin and platelet levels as triggers for transfusion support; the use of prophylactic antibiotics; and follow-up monitoring after completion of treatment.These initial survey results reflect heterogeneity in diagnosis and care amongst pediatric centers and emphasize the need to develop evidence-based diagnosis and treatment approaches in this rare disease. Pediatr Blood Cancer 2013;9999:1-6. © 2013 Wiley Periodicals, Inc.
- [The variation and clinical significance of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia before and after immunosuppressive therapy]. [English Abstract, Journal Article]
- Zhonghua Nei Ke Za Zhi 2013 Jul; 52(7):585-9.
To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA).A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyteglobulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months.Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t = 5.041, P = 0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and > 24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values < 0.05). Clinical response rates were comparable in both ATG+CsA or CsA alone groups no matter PNH clone was positive or negative.PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurres before or after IST does not affect the therapeutic efficacy.
- Korean guideline for iron chelation therapy in transfusion-induced iron overload. [Journal Article, Review]
- J Korean Med Sci 2013 Nov; 28(11):1563-72.
Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.
- Reduced intensity conditioning and co-transplantation of unrelated peripheral stem cells combined with umbilical cord mesenchymal stem/stroma cells for young patients with refractory severe aplastic anemia. [JOURNAL ARTICLE]
- Int J Hematol 2013 Nov 22.
Five young patients with a long history of severe aplastic anemia (SAA) who had failed initial CSA treatment and lacked a HLA-matched sibling donor, underwent co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) and umbilical cord mesenchymal/stroma stem cells (UC-MSCs). After FLU + CTX + ATG ± 2GY TBI conditioning, all patients received UD-PBSCs and UC-MSCs. There were no side effects attributable to the infused MSCs, and no severe complications or infections were observed in any patient after transplantation. After transplantation, one patient experienced primary graft failure, the reason for which may be related to a long history (>17 years) of SAA. The other four patients achieved complete hematopoietic recovery and complete donor hematopoietic chimerism. We did not observe severe aGVHD or cGVHD. These data suggest that co-transplantation of UD-PBSCs and UC-MSCs is an acceptable alternative treatment for young patients with a long history of intensively treated SAA.
- Acquired aplastic anemia in children. [Journal Article]
- Pediatr Clin North Am 2013 Dec; 60(6):1311-36.
This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.