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Hematology AND Aplastic anemia [keywords]
- Epidemiologic and HLA Antigen Profile in Patients with Aplastic Anemia. [Journal Article]
- J Coll Physicians Surg Pak 2014 Aug; 24(8):549-52.
To analyze patients suffering from aplastic anemia (AA, peripheral pancytopenia and hypocellular bone marrow in the absence of dysplasia, infiltration and fibrosis) for documenting patient's baseline characteristics and association with various human leucocyte antigens.An observational, cross-sectional study.The National Institute of Blood Disease (NIBD), Karachi, from March 2003 to August 2008.All consecutive patients with confirmed diagnosis of AA were evaluated. Data included the baseline characteristics, complete blood counts (CBC), bone marrow biopsy findings, severity of disease, exposure to drugs or chemicals, viral serology and their HLA expression. The data was analyzed on SPSS programme and frequencies were documented.Among 318 patients, there were 236 (74.21%) males and 82 (25.78%) females. Median age was 16 and 70% belonged to urban population. Drug exposure could be established in 23 (7.23%) of cases, while 4 (1.25%) were HBV surface antigen positive and 7 (2.2%) were HCV antibodies positive. In all, 73 (22.9%) had very severe AA, 195 (61.32%) had severe AA while 50 (15.7%) cases had non-severe AA. HLA B5 (52) showed high expression in 83 patients (26%) in comparison to 5.9% reported in healthy population.AA was found to affect young adult males living in urban areas. HLA B5 (52) showed higher expression in patients with aplastic anemia.
- Reduced-intensity stem cell allografting for PNH patients in the eculizumab era: The Mexican experience. [JOURNAL ARTICLE]
- Hematology 2014 Aug 22.
Background Paroxysmal nocturnal haemoglobinuria (PNH) presents as two major entities: the classical form, predominantly haemolytic and a secondary type with marrow failure and resultant aplastic anaemia (AA-PNH). Currently, the treatment of choice of the haemolytic variant is eculizumab; however, the most frequent form of PNH in México is AA-PNH. Patients and methods Six consecutive AA-PNH patients with HLA-identical siblings were allografted in two institutions in México, employing a reduced-intensity conditioning regimen for stem cell transplantation (RIST) conducted on an outpatient basis. Results Median age of the patients was 37 years (range 25-48). The patients were given a median of 5.4 × 10(6)/kg allogeneic CD34(+) cells, using 1-3 apheresis procedures. Median time to achieve above 0.5 × 10(9)/l granulocytes was 21 days, whereas median time to achieve above 20 × 10(9)/l platelets was 17 days. Five patients are alive for 330-3150 days (median 1437) after the allograft. The 3150-day overall survival is 83.3%, whereas median survival has not been reached, being above 3150 days. Conclusion We have shown that hypoplastic PNH patients can be allografted safely using RIST and that the long-term results are adequate, the cost-benefit ratio of this treatment being reasonable. Additional studies are needed to confirm the usefulness of RIST in the treatment of AA-PNH.
- [Association between serum interleukin-17 level and abnormal celluar immunological status in patients with severe aplastic anemia]. [English Abstract, Journal Article]
- Zhonghua Yi Xue Za Zhi 2014 May 27; 94(20):1539-42.
To explore the role of interleukin-17 (IL-17) in the pathogenesis of severe aplastic anemia (SAA).Peripheral blood samples were obtained from 40 SAA patients (25 untreated, 15 recovery) and 10 normal controls from October 2012 to October 2013. The level of IL-17 in peripheral blood was measured with cytometric bead array (CBA). The correlations between IL-17 and T cells subset (CD4(+)/CD8(+)), dendritic cells (DC) subset (mDC/pDC), regulatory T cells (Treg) and hemogram were analyzed.The serum level of IL-17 in untreated patients was higher than that in recovery patients and normal controls ((17.07 ± 15.18) vs (7.09 ± 3.84) and (3.53 ± 2.08) ng/L, both P < 0.01). Also significant differences existed between the latter two groups (P < 0.05). The ratio of CD4(+)/CD8(+) was (0.32 ± 0.08) in untreated patients and it was lower than that in recovery patients (1.11 ± 0.31, P < 0.01) and normal controls (1.07 ± 0.26, P < 0.01). The ratio of mDC/pDC was (3.16 ± 0.55) in untreated patients was higher than that in recovery patients (1.60 ± 0.43, P < 0.01)and normal controls (1.43 ± 0.38, P < 0.01). The percentage of Tregs in peripheral blood lymphocyte (CD4(+)CD25(+)CD127(dim)/PBL) was 0.80% ± 0.31% in untreated patients and it was lower than that in recovery patients (1.78% ± 0.69%, P < 0.01) and normal controls (2.23% ± 0.66%, P < 0.01). The serum level of IL-17 in untreated SAA patients was related positively with mDC/pDC ratio (r = 0.414, P < 0.05) and negatively with CD4(+)/CD8(+) ratio (r = -0.421, P < 0.05) and CD4(+)CD25(+)CD127(dim)/PBL(r = -0.650, P < 0.01). And significant negative correlations existed between serum IL-17 and white blood cells in untreated patients (r = -0.689, P < 0.01) and recovery patients (r = -0.640, P < 0.05).The elevated serum level of IL-17 in SAA is related with the immunological status and disease severity.
- [The outcome of thirteen patients with nonmalignant hematologic diseases treated with HLA haploidentical stem cell transplantation]. [English Abstract, Journal Article]
- Zhonghua Nei Ke Za Zhi 2014 Jun; 53(6):473-6.
To evaluate the clinical efficacy and safety of human leukocyte antigen (HLA) haploidentical stem cell transplantation in nonmalignant hematologic diseases.To analyze the outcome of 13 patients with nonmalignant hematologic diseases who underwent HLA haploidentical stem cell transplantation from September 2001 to October 2013.Thirteen patients including 9 of severe aplastic anemia, 3 of severe β thalassemia, 1 of congenital pure red cell aplastic anemia underwent HLA haploidentical stem cell transplantation. Three HLA loci mismatched in 4 cases, two HLA loci mismatched in 8 cases and one HLA locus mismatched in 1 case. The conditioning regime consisted of Fludarabine (30 mg×m(-2)×d(-1)×5 d ), Busulfan(0.8 mg×kg(-1)×6h(-1)×4 d), Cyclophosphamide (60 mg×kg(-1)×d(-1)×2 d ), rabbit anti-human lymphocyte globulin ( 2.5 mg×kg(-1)×d(-1)×5 d ). To prevent from graft-versus-host disease (GVHD), cyclosporin A and short term methotrexate (MTX) were used. All patients were successfully engrafted. The incidence of grade 1-2 acute graft-versus-host disease (aGVHD) was 3/13, and that of grade 3-4 was 1/13. The cumulative incidence of total chronic GVHD (cGVHD) was 3/13. Eleven patients survived free of disease at a median follow-up period of 13 months (2-145).HLA haploidentical stem cell transplantation is an effective and safe therapy for nonmalignant hematologic diseases.
- Somatic mutations identify a sub-group of aplastic anemia patients that progress to myelodysplastic syndrome. [JOURNAL ARTICLE]
- Blood 2014 Aug 18.
Aplastic anemia (AA) is a heterogeneous disorder. The distinction between acquired AA and hypocellular myelodysplastic syndrome (hMDS) is often difficult, especially non-severe AA. Definition of hMDS is based solely on morphological changes in blood and bone marrow. We postulated that somatic mutations are present in a subset of AA, and predict malignant transformation. From our database of 345 AA patients, we identified 150 patients with no morphological evidence of MDS, who had stored BM and constitutional DNA. We excluded Fanconi anemia, mutations of telomere maintenance, and a family history of bone marrow failure (BMF) or cancer. The initial cohort of 57 patients was screened for 835 known genes associated with BMF and myeloid cancer; a second cohort of 93 patients was screened for mutations in ASXL1, DNMT3A, BCOR, TET2, and MPL. Somatic mutations were detected in 19% of AA, and included ASXL1 (n=12), DNMT3A (n=8) and BCOR (n=6). Patients with somatic mutations had a longer disease duration (37 vs. 8 months, p<0.04), and shorter telomere lengths (median T/S length, 0.9 vs. 1.1, p<0.001), compared to patients without mutations. Somatic mutations in AA patients with disease duration of > 6 months were associated with 40% risk of transformation to MDS (p <0.0002). Nearly a fifth of AA patients harbor mutations in genes typically seen in myeloid malignancies that predicted for later transformation to MDS.
- Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children and adolescents with acquired severe aplastic anemia. [JOURNAL ARTICLE]
- Bone Marrow Transplant 2014 Aug 18.
Haploidentical hematopoietic SCT (haplo-HSCT) is to be established in patients with acquired severe aplastic anemia (SAA) refractory to immunosuppressive therapy and lacking HLA-matched related or unrelated donors. Graft failure (GF) and GVHD have been major obstacles to HSCT. A total of 17 children and adolescents with SAA underwent haplo-HSCT in our center. The conditioning regimen consisted of BU, fludarabine, CY and anti-thymocyte globulin. All patients received cyclosporine, short-term MTX, mycophenolate mofetil and basiliximab for GVHD prophylaxis. Mesenchymal stem cells derived from unrelated umbilical cord were infused on day 1. Neutrophil engraftment was achieved in all 17 patients in a median time of 16 days (range 9-25 days). The median time of platelet engraftment was 22 days (range 9-95 days) in 16 patients. The cumulative incidence (CI) of II-IV acute GVHD (aGVHD) at day +100 was 30.53±11.12% and III-IV aGVHD occurred in only one patient. The CI of chronic GVHD was 21.25±13.31%. Secondary GF with autologous hematopoiesis recovery occurred in one patient. The OS was 71.60±17.00% at a median follow-up of 362 (36-1321) days. These limited promising data suggest that haplo-HSCT is feasible as a salvage therapy for children and adolescents with refractory SAA who lack matched donors.Bone Marrow Transplantation advance online publication, 18 August 2014; doi:10.1038/bmt.2014.187.
- Severity stratification of aplastic anemia. [Journal Article]
- Chin Med J (Engl) 2014 Aug; 127(16):3040.
- [Abnormal quantity of regulatory T cells in peripheral blood of patients with severe aplastic anemia and its clinical significance]. [English Abstract, Journal Article]
- Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Jul; 22(4):1043-6.
This study was purposed to investigate the role of regulatory T cells (Treg) in the immune unbalance for patients with acquired severe aplastic anemia (SAA). The flow cytometry was used to detect the quantity of CD4(+) CD25(+) CD127(dim) Tregs, T cell subset (CD4(+)/CD8(+) ratio), dendritic cell(DC) subset(mDC/pDC ratio) in 44 SAA patients(25 untreated patients and 19 recovery patients) and 23 normal controls. The correlation between Tregs and T cell subset, DC subset and hemogram were analyzed. The results showed that the percentage of CD4(+) CD25(+) CD127(dim) Tregs in peripheral blood lymphocyte(PBL) of untreated patients was (0.83 ± 0.44) %, which was obviously lower than that in recovery patients (2.91 ± 1.24)% and normal controls (2.18 ± 0.55)% (P < 0.05), but the difference was not statistically significant between latter two groups. The ratio of CD4(+)/CD8(+) was (0.5 ± 0.3) in untreated patients, which was obviously lower than that in recovery patients (1.2 ± 0.4) and normal controls (1.11 ± 0.24) (P < 0.05). The ratio of mDC/pDC was (3.08 ± 0.72) in untreated patients, which was significantly higher than that in recovery patients(1.61 ± 0.49) and normal controls (1.39 ± 0.36) (P < 0.05). The percentage of CD4(+) CD25(+)CD127(dim) Tregs in PBL positively correlated with CD4(+)/CD8(+) ratio (r = 0.695, P < 0.01), and that negatively correlated with mDC/pDC ratio (r = -0.796, P < 0.01). There were significant positive correlations between CD4(+)CD25(+)CD127(dim) Tregs/PBL and WBC, Ret% (r = 0.761, 0.749 respectively, P < 0.01). It is concluded that the decrease of CD4(+)CD25(+)CD127(dim) Tregs quantity in SAA may be one of mechanisms underlying bone marrow failure resulting from the deterioration of immune tolerance and hyperfunction of T-cells.
- [Expressive Changes of CD4(+)T Cell Subset Transcription Factors in Patients with Aplastic Anemia, Myelodysplastic Syndrome and Acute Myeloid Leukemia and Their Clinical Significances]. [English Abstract, Journal Article]
- Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Jul; 22(4):1038-42.
This study was aimed to compare the expressions of specific transcription factors of CD4(+) T cell subset ( T-bet, GATA-3, RORγt and FoxP3 mRNA) in peripheral blood of patients with aplastic anemia(AA), myelodysplastic syndrome(MDS), and acute myeloid leukemia(AML), and investigate their immune status and pathogenesis, so as to provide experimental basis for the choice of clinical treatment. The expression of T-box (T-bet), GATA-3, ROR-γt and Foxp3 mRNA in PBMNC were examined by RT-PCR in 42 cases of MDS, including 22 refractory anemia(MDS-RA) and 20 refractory anemia with excess blasts (MDS-RAEB), in 23 cases of AA, 17 cases of AML patients and 16 healthy volunteers respectively. The results indicated that, compared with normal control group, expressions of T-bet and RORγt mRNA in AA patient group were significantly higher (P < 0.01), expression levels of GATA3 Foxp3 mRNA were lower (both P < 0.01). There was no significant difference in expression of T-bet and GATA3 mRNA between MDS group and normal control group, but the expression levels of Foxp3 and RORγt mRNA were higher than those in normal controls (P < 0.05); T-bet and RORγt in MDS-RA group were higher than those in the normal controls(P < 0.01), and GATA3 expression significantly reduced (P < 0.05), however, there was no significant difference in expression of Foxp3 between MDS-RA and the controls. Expression levels of T-bet and RORγt mRNA in patients with MDS-RAEB and AML were lower than those in normal controls (P < 0.05), but the expression levels of GATA3 and Foxp3 mRNA were significantly higher than those in normal controls (P < 0.01). It is concluded that the transcription factor expressions are different in PBMNC of patients among these three diseases. Immune-mediated excessive apoptosis may play an important role in pathogenesis, bone marrow failure in patients with AA and MDS-RA, and abnormal clones of immature cells may be one of main reasons for bone marrow failure in AML and late stage of MDS.
- Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT. [JOURNAL ARTICLE]
- Clin Transplant 2014 Aug 14.
Graft failure and survival are major problems for aplastic anemia patients undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact graft failure in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic-HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse 5-year survival (78.6% vs 100%, p=0.021) and higher treatment-related mortality (21.4% vs 0%, p=0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer 5-year survival (75.0%) than anti-HLA class I&II antibody-positive and -negative patients (87.5% and 100.0% respectively, p=0.039). Presence of anti-HLA class I antibodies (p=0.024) and older age (10yrs or more) (p=0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric aplastic anemia patients. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT. This article is protected by copyright. All rights reserved.