- Aplastic Anemia and Risk of Incident Atrial Fibrillation - A Nationwide Cohort Study. [Journal Article]
- CJCirc J 2018 Feb 16
- CONCLUSIONS: Patients with AA could have an elevated risk for AF. The mortality risk increased further for those who develop AF.
- Clinical characteristics and treatment outcomes of pulmonary invasive fungal infection among adult patients with hematological malignancy in a medical centre in Taiwan, 2008-2013. [Journal Article]
- JMJ Microbiol Immunol Infect 2018 Jan 31
- CONCLUSIONS: Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.
- How I treat myelodysplastic syndromes of childhood. [Journal Article]
- BloodBlood 2018 Feb 08
- Pediatric myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders with an annual incidence of 1-4 cases/million, accounting for less than 5% of childhood hematological malignanc...
Pediatric myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders with an annual incidence of 1-4 cases/million, accounting for less than 5% of childhood hematological malignancies. MDS in children often occur in the context of inherited bone marrow failure syndromes, this representing a peculiarity of myelodysplasia diagnosed in the pediatric age. Moreover, germline syndromes predisposing individuals to develop MDS/acute myeloid leukemia have recently been identified, such as those caused by mutations inGATA2, ETV6, SRP72,andSAMD9/SAMD9-LRefractory cytopenia of childhood (RCC) is the most frequent pediatric MDS variant, showing specific histopathological features. Allogeneic hematopoietic stem cell transplantation (HSCT) represents the treatment of choice for many children with MDS, being routinely offered to all patients with MDS with excess of blasts, to those with MDS secondary to previously administered chemo-radiotherapy, and to those with RCC associated with either monosomy 7, complex karyotype or severe neutropenia or transfusion dependence. Immune-suppressive therapy may be a treatment option for RCC patients with hypocellular bone marrow and absence of monosomy 7 or complex karyotype, although the response rate is lower than that observed in severe aplastic anemia, and a relevant proportion of these patients will subsequently need HSCT for either non-response or relapse.
- Isolated splenic mucormycosis in a case of aplastic anaemia. [Journal Article]
- BCBMJ Case Rep 2018 Feb 08; 2018
- Mucormycosis, a rare opportunistic infection seen in immunocompromised hosts, is caused by fungi of Mucorales family. It may be confined to the organs, such as rhinocerebral and pulmonary mucormycosi...
Mucormycosis, a rare opportunistic infection seen in immunocompromised hosts, is caused by fungi of Mucorales family. It may be confined to the organs, such as rhinocerebral and pulmonary mucormycosis, or may cause disseminated infection. A 14-year-old boy presented to our clinic with fever and left upper quadrant abdominal pain, and on evaluation was found to have pancytopaenia, and imaging revealed ill-defined splenic collection with thrombus in the splenic vein. He was started on empirical intravenous antibiotics, followed by antifungals empirically as he did not show any improvement clinically. Eventually, splenectomy was done, which on histopathological examination revealed mucormycosis. The patient finally succumbed to his illness as he developed peritonitis and refractory shock. To date, only two cases of isolated splenic mucormycosis have been reported. Aggressive treatment is needed, which includes the use of antifungals (amphotericin B) and surgical debridement or resection of the involved tissues or organs.
- Efficacy and safety of combined immunosuppressive therapy plus umbilical cord blood infusion in severe aplastic anemia patients: A cohort study. [Journal Article]
- ETExp Ther Med 2018; 15(2):1966-1974
- The present study aimed to evaluate the efficacy and safety of combined immunosuppressive therapy (IST) plus umbilical cord blood infusion (UCBI) in severe aplastic anemia (SAA) patients. A total of ...
The present study aimed to evaluate the efficacy and safety of combined immunosuppressive therapy (IST) plus umbilical cord blood infusion (UCBI) in severe aplastic anemia (SAA) patients. A total of 68 patients with SAA were enrolled in the current prospective cohort study and divided into the IST (n=35; positive control) and IST+UCBI (n=33; experimental) groups according to the treatment conditions. Patients in the IST group were treated with rabbit antithymocyte globulin (r-ATG) at a dose of 2.5 mg/kg through intravenous infusion once a day for five days. This was combined with oral cyclosporine A (CsA) at a dose of 3-5 mg/kg twice a day for 2 years. Patients in the IST+UBCI group were treated with r-ATG and CsA at the same doses and frequencies as the IST group plus one UCBI 1 day after the final treatment with r-ATG. At 6 months post treatment, the complete response and overall response rate (ORR) of the IST+UCBI group were markedly higher compared with those in the IST group. Furthermore, patients in the IST+UCBI group achieved absolute neutrophil count (ANC) and platelet count responses more rapidly as compared with the IST group. However, no difference in the hemoglobin (Hb) response was identified between the two groups. In addition, SAA patients achieved responses in the ANC and platelet count more rapidly in comparison with very severe aplastic anemia (VSAA) patients, while the number of days to Hb responses were similar in the SAA and VSAA patients. Multivariate logistic regression analysis also revealed that IST+UCBI treatment was an independent predicting factor for patients achieving complete response or partial response, whereas VSAA was an independent predictor of a worse ORR. Platelet and reticulocyte were also independent predicting factors. Finally, the survival of patients was similar between the groups, and no difference in the safety of the treatment was observed. In conclusion, combined IST plus UCBI treatment may be applied as an effective and safe therapy for SAA patients.
- A composite mouse model of aplastic anemia complicated with iron overload. [Journal Article]
- ETExp Ther Med 2018; 15(2):1449-1455
- Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal d...
Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.
- Allogeneic Matched Related Donor Bone Marrow Transplantation for Pediatric Patients With Severe Aplastic Anemia Using "Low-dose" Cyclophosphamide, ATG Plus Fludarabine. [Journal Article]
- JPJ Pediatr Hematol Oncol 2018 Feb 09
- CONCLUSIONS: This small pilot study shows that this cytoreductive regimen could be considered as the standard of care for transplantation of pediatric patients with aplastic anemia from HLA-matched siblings.
- Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor Vβ oligoclonality and CDR3 homology in acquired aplastic anemia. [Journal Article]
- HHaematologica 2018 Feb 01
- Oligoclonal expansion of CD8+CD28- lymphocytes has been considered indirect evidence for a pathogenic immune response in acquired aplastic anemia. A subset of CD8+CD28- cells with CD57 expression ter...
Oligoclonal expansion of CD8+CD28- lymphocytes has been considered indirect evidence for a pathogenic immune response in acquired aplastic anemia. A subset of CD8+CD28- cells with CD57 expression termed effector memory cells is expanded in several immune mediated diseases and may have a role in immune surveillance. We hypothesized that effector memory CD8+CD28-CD57+ cells may drive aberrant oligoclonal expansion in aplastic anemia. We found CD8+CD57+ cells frequently expanded in the blood of aplastic anemia patients, with oligoclonal characteristics by flow cytometric Vβ usage analysis: skewing in 1 to 5 Vβ families and frequencies of immunodominant clones ranging from 1.98% to 66.5%. Oligoclonal characteristics were also observed in total CD8+ cells from aplastic anemia patients with CD8+CD57+ cell expansion by T-cell receptor deep sequencing, as the presence of 1 to 3 immunodominant clones. Oligoclonality was confirmed by T-cell receptor repertoire deep sequencing of enriched CD8+CD57+ cells, which showed also decreased diversity compared to total CD4+ and CD8+ cell pools. From analysis of complementarity-determining region 3 sequences in the CD8+ cell pool, a total of 29 sequences were shared between patients and controls, but these sequences were highly expressed in aplastic anemia subjects and also present in their immunodominant clones. In summary, expansion of effector memory CD8+ T cells is frequent in aplastic anemia and mirrors Vβ oligoclonal expansion. Flow cytometric Vβ usage analysis combined with deep sequencing technologies allows high resolution characterization of the T-cell receptor repertoire, and might represent useful tools in diagnosis and periodic evaluation of aplastic anemia patients.
- Fanconi Anemia germline variants as susceptibility factors in aplastic anemia, MDS and AML. [Journal Article]
- OOncotarget 2018 Jan 05; 9(2):2050-2057
- Using next generation sequencing we have systematically analyzed a large cohort of 489 patients with bone marrow failure (BMF), including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML),...
Using next generation sequencing we have systematically analyzed a large cohort of 489 patients with bone marrow failure (BMF), including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), aplastic anemia (AA), and related conditions for the presence of germline (GL) alterations in Fanconi Anemia (FA) and telomerase genes. We have detected an increased frequency of heterozygous FA gene mutations in MDS and to lesser degree in AML suggesting that the presence of one normal allele may not be completely protective and indeed heterozygous FA lesions may have a long latency period before hematologic manifestation. In contrast, GL telomerase gene mutations were not associated with increased disease risk. When compared to large control cohorts, we have not detected an increased frequency of damaging variants among telomerase complex genes, including those previously believed to be involved in the pathogenesis of AA. Our results may suggest that while low penetrance and delayed disease onset can confound identification of genetic predisposition factors, GL FA alterations can be also associated with MDS.
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- [Reduced-intensity umbilical cord blood transplantation for adult patients with fulminant aplastic anemia]. [Journal Article]
- RKRinsho Ketsueki 2018; 59(1):64-68
- Allogeneic hematopoietic stem cell transplantation is recommended as a curative treatment option for fulminant aplastic anemia with no neutrophil despite the administration of granulocyte-colony stim...
Allogeneic hematopoietic stem cell transplantation is recommended as a curative treatment option for fulminant aplastic anemia with no neutrophil despite the administration of granulocyte-colony stimulating factor. In the absence of an HLA-matched donor, unrelated cord blood transplantation (UCBT) is a treatment option that can be performed quickly. However, the optimal conditioning regimen of UCBT is yet to be established. We report two cases of fulminant aplastic anemia in adult patients who received UCBT. The first patient was a 52-year-old woman and the second was a 26-year-old man, both of whom received a conditioning regimen of total body irradiation (TBI; 2-4 Gy), fludarabine (Flu; 120 mg/kg), and cyclophosphamide (CY; 100 mg/kg) before UCBT. Short-term methotrexate and tacrolimus were used for prophylaxis of acute graft-versus-host disease (GVHD). Engraftments were achieved on days 26 and 19, and they exhibited complete donor chimerism by days 28 and 34. There was no evidence of acute GVHD, and therefore, the immunosuppressant drugs were discontinued. Reduced-intensity UCBT using a low-dose TBI/Flu/CY conditioning regimen could be an effective treatment option for fulminant aplastic anemia in the absence of a suitable donor.