- Glycosylphosphatidylinositol-specific T cells,IFNγ-producing T cells,and pathogenesis of idiopathic aplastic anemia. [Journal Article]
- BloodBlood 2016 Nov 30
- Left main crossover stenting in a patient with severe thrombocytopenia due to aplastic anemia. [Journal Article]
- CICardiovasc Interv Ther 2016 Nov 24
- A 76-year-old man with aplastic anemia presented with recurrent acute myocardial infarction (AMI) with heart failure. After the initial appearance of AMI approximately 2 months earlier, he had receiv...
A 76-year-old man with aplastic anemia presented with recurrent acute myocardial infarction (AMI) with heart failure. After the initial appearance of AMI approximately 2 months earlier, he had received conservative treatment/transfusion alone because of severe thrombocytopenia and anemia (platelet 11 × 10(3)/μL, hemoglobin 6.4 g/dL). Refractory heart failure persisted despite repeated conservative treatment/transfusion for the second AMI, and therefore, we performed transradial coronary angiography and left main crossover stenting with a bare metal stent. His critical condition markedly improved; however, soon after discharge, he complicated with subdural hematoma. He has since been free of cardiovascular/hemorrhagic events for 7 months without antiplatelet/anticoagulant therapy.
- Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review. [Review]
- IJInt J Nephrol 2016; 2016:5163789
- Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. How...
Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality. The incidence of AKI reported in recipients of myeloablative allogeneic transplant is considerably higher in comparison to other subclasses mainly due to use of cyclosporine and development of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself a major independent risk factor for the development of AKI in HSCT recipients. The other major risk factors are sepsis, nephrotoxic medications (amphotericin B, acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and tumor lysis syndrome. The mainstay of management of AKI in these patients is avoidance of risk factors contributing to AKI, including use of reduced intensity-conditioning regimen, close monitoring of nephrotoxic medications, and use of alternative antifungals for prophylaxis against infection. Also, early identification and effective management of sepsis, tumor lysis syndrome, marrow infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT recipients.
- Etiological causes of pancytopenia: A report of 137 cases. [Journal Article]
- AJAvicenna J Med 2016 Oct-Dec; 6(4):109-112
- CONCLUSIONS: The etiological causes of pancytopenia vary depends on patients' age, gender, country, and other conditions. Vitamin B12 deficiency is the most common treatable cause of pancytopenia. Most of the etiological causes could be diagnosed with laboratory analysis and radiological imagings, without the need of a bone marrow examination.
- Development of a disease-specific quality of life questionnaire for patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria (QLQ-AA/PNH)-report on phases I and II. [Journal Article]
- AHAnn Hematol 2016 Nov 11
- Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated ultra-rare diseases. Quality of life (QoL) evaluation tools used in studies for AA and PNH are unspecific ...
Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated ultra-rare diseases. Quality of life (QoL) evaluation tools used in studies for AA and PNH are unspecific and designed for cancer patients (e.g., the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30). Given the complexity of AA and PNH, variation in symptoms and treatments, younger age of many patients, and the fact that AA and PNH are not classified as malignant diseases, it is likely that cancer-specific questionnaires are inappropriate. We generate an AA/PNH-specific QoL questionnaire (QLQ-AA/PNH), performed according to EORTC guidelines. QoL issues were obtained from the literature and interviews with patients and physicians (phase I), then ranked by patients and physicians. In phase II, items were created. Patients in more than 25 German and Swiss cities were interviewed face to face. In phase I, interviews of 19 patients and 8 physicians specialized in AA/PNH treatment resulted in 649 QoL issues; these were condensed to 175 and graded according to their importance by 30 patients and 14 physicians (phase II). Five physicians took part in phases I and II. Altogether, 97 issues were rated important. Twelve EORTC QLQ-C30 items were not rated important, while several new QoL aspects were brought up. Modifications in wording and phrasing led to two questionnaires with 77 items regarding general QoL aspects and 20 items regarding medical care. Important QoL aspects of PNH/AA patients are inappropriately captured with available QoL tools. Developing a new QoL questionnaire specific for this patient group is warranted.
- Mixed T Cell Chimerism After Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using an Alemtuzumab-Containing Regimen Is Shaped by Persistence of Recipient CD8 T Cells. [Journal Article]
- BBBiol Blood Marrow Transplant 2016 Nov 2
- Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT f...
Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90.7%. Acute and chronic GVHD each occurred in 6 patients (13.3%), and only 1 case was severe. Mixed T-cell chimerism was frequent and persisted after cessation of postgrafting immunosuppression. T cells were extensively depleted, composing only 11.3% of lymphocytes at day +30 and rising to 43.8% by 1 year, but still significantly below normal levels (67.2%; P = .018), and deficiency persisted after immunosuppressive therapy withdrawal. Depletion of CD4 T cells was particularly profound, causing inversion of the normal CD4:CD8 T cell ratio. T cell subset composition was also abnormal, with memory and effector T cells predominating for at least 6 months after FCC HSCT. Analysis of T cell subset chimerism showed that CD4 T cells were predominantly donor-derived at 1 year, whereas recipient-derived CD8 T cells shaped mixed chimerism with a notable contribution of recipient effector CD8 T cells. The prolonged mixed T cell chimerism after withdrawal of postgrafting immunosuppression and low incidence of GVHD indicates the establishment of mutual tolerance, but the low incidence of viral disease suggests maintenance of antiviral immunity. Our study shows that despite the abnormal T cell profile after allogeneic HSCT for SAA using the FCC regimen, this regimen is conducive to an excellent clinical outcome.
- Blood Stem Cell Activity Is Arrested by Th1-Mediated Injury Preventing Engraftment following Nonmyeloablative Conditioning. [Journal Article]
- JIJ Immunol 2016 Nov 15; 197(10):4151-4162
- T cells are widely used to promote engraftment of hematopoietic stem cells (HSCs) during an allogeneic hematopoietic cell transplantation. Their role in overcoming barriers to HSC engraftment is thou...
T cells are widely used to promote engraftment of hematopoietic stem cells (HSCs) during an allogeneic hematopoietic cell transplantation. Their role in overcoming barriers to HSC engraftment is thought to be particularly critical when patients receive reduced doses of preparative chemotherapy and/or radiation compared with standard transplantations. In this study, we sought to delineate the effects CD4(+) cells on engraftment and blood formation in a model that simulates clinical hematopoietic cell transplantation by transplanting MHC-matched, minor histocompatibility-mismatched grafts composed of purified HSCs, HSCs plus bulk T cells, or HSCs plus T cell subsets into mice conditioned with low-dose irradiation. Grafts containing conventional CD4(+) T cells caused marrow inflammation and inhibited HSC engraftment and blood formation. Posttransplantation, the marrows of HSCs plus CD4(+) cell recipients contained IL-12-secreting CD11c(+) cells and IFN-γ-expressing donor Th1 cells. In this setting, host HSCs arrested at the short-term stem cell stage and remained in the marrow in a quiescent cell cycling state (G0). As a consequence, donor HSCs failed to engraft and hematopoiesis was suppressed. Our data show that Th1 cells included in a hematopoietic allograft can negatively impact HSC activity, blood reconstitution, and engraftment of donor HSCs. This potential negative effect of donor T cells is not considered in clinical transplantation in which bulk T cells are transplanted. Our findings shed new light on the effects of CD4(+) T cells on HSC biology and are applicable to other pathogenic states in which immune activation in the bone marrow occurs such as aplastic anemia and certain infectious conditions.
- [Analysis of clinical characteristics and prognosis of non-severe aplastic anemia children with chromosomal abnormalities]. [Journal Article]
- ZEZhonghua Er Ke Za Zhi 2016 Nov 2; 54(11):814-818
- Objective: To analyze the clinical characteristics and prognosis of non-severe aplastic anemia (NSAA) with chromosomal abnormalities in children. Method: A retrospective analysis of 304 cases with NS...
Objective: To analyze the clinical characteristics and prognosis of non-severe aplastic anemia (NSAA) with chromosomal abnormalities in children. Method: A retrospective analysis of 304 cases with NSAA with successful karyotyping from 2001 to 2014 in the Institute of Hematology & Blood Disease Hospital was carried out. The treatment response, condition of blood transfusion were analyzed using χ(2) test, the cumulative survival was estimated by the Kaplan-Meier method. Result: Out of 304 patients, 28 patients had chromosomal abnormalities with trisomy 8 (7 cases, 25.0%), abnormalities in chromosome 7 (5 cases, 17.9%), and other types (16 cases, 57.1%). There were no significant differences in the treatment response(40.9% (9/22)vs. 58.6%(119/203), χ(2)=2.539, P=0.111), the rate of getting rid of blood transfusion(54.5%(6/11) vs. 65.0%(39/60), χ(2)=6.455, P=0.086), five-year progression-free survival (49.2% vs.70.8%, χ(2)=0.849, P=0.357), and five-year cumulative survival (79.1% vs. 92.8%, χ(2)=0.330, P=0.556) between the patients with or without chromosomal abnormalities. There were significant differences in the rate of disease progression(41.7%(10/24) vs. 22.3%(48/215), χ(2)=4.394, P=0.045), the incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (20.8%(5/24)vs. 0.9%(2/215), χ(2)=30.082, P=0.000)and the five-year cumulative incidence of MDS or AML(33.4% vs. 0.8%, χ(2)=17.798, P=0.000)between children with and without chromosomal abnormalities. Conclusion: The incidence of chromosomal abnormalities in children with NSAA is 9.2%. The clinical features and treatment response are similar, but children with chromosomal abnormalities have a poorer prognosis, and have higher risk of progressing to MDS or AML.
- Are mild/moderate acquired idiopathic aplastic anaemia and low-risk myelodysplastic syndrome one or two diseases or both and how should it/they be treated? [Editorial]
- LLeukemia 2016; 30(11):2127-2130
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- 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. [Journal Article]
- BMBone Marrow Transplant 2016; 51(11):1456-1463
- 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, l...
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.