Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANEMIA, APLASTIC”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2000

N-RAS gene mutation in patients with aplastic anemia and aplastic anemia/ paroxysmal nocturnal hemoglobinuria during evolution to clonal disease.

Long-term survivors of aplastic anemia (AA) have a high incidence of clonal disorders, in particular paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndromes (MDS), and acute nonlymphocytic leukemia. To investigate the potential involvement of N-RAS gene mutations in the predisposition to leukemic evolution, a subset of patients at potentially increased risk for clonal disease was selected based on evidence of existing clonal evolution. Nine patients showed a monoclonal pattern of X-chromosome inactivation, 18 demonstrated a PNH clone, and in 3 MDS developed during the course of this study. No mutations were detected during the aplastic phase of disease; 2 of 3 patients with MDS after AA also showed no mutations. However, in 1 patient in whom the disease transformed from AA/PNH to MDS, a mutation of GGT --> GAT at N-RAS codon 13 became detectable, whereas the PNH mutation disappeared. The authors conclude that N-RAS mutations are not an early event preceding transformation of AA or AA/PNH to leukemia. In a subset of patients, RAS mutations may occur at the time of evolution to MDS, but preexisting RAS mutations do not explain the propensity of AA to leukemogenesis. Although PNH is also associated with leukemia, this may arise in the non-PNH cells, indicating that PIG-A gene mutation is not per se oncogenic. (Blood. 2000;95:646-650)

Adult↗
PubMed2002

Screening for paroxysmal nocturnal hemoglobinuria (PNH) clone in Egyptian children with aplastic anemia.

Aplastic anemia and paroxysmal nocturnal hemoglobinuria (PNH) are clinically related. In addition to their concurrent or sequential appearance in individual patients, PNH and aplastic anemia share several pathophysiologic features. The aim of the present study was to screen for PNH clone in Egyptian aplastic anemia pediatric patients before the initiation of any specific therapy and to evaluate the clinical status of studied patients 3-6 months after initiation of immunosuppressive therapy. We studied 11 pediatric patients with newly diagnosed acquired aplastic anemia and followed them up clinically for 3-6 months after initiation of immunosuppressive therapy. In addition to routine clinical and laboratory evaluation, sucrose lysis test and staining of bone marrow for CD59 were performed in all subjects. All studies cases had severe aplastic anemia (SAA) except one case which had very severe aplastic anemia (VSAA). Sucrose lysis test was negative in all studied cases. Presence of PNH clone (as evident by loss of normal staining of hematopoietic cells for CD59 = CD59 negative cells) was evident in four subjects. All cases with PNH clone were >6 years old and one of them developed splenic vein thrombosis. As regards the laboratory data WBC < or = 2.8 x 10(3)/mm3 and reticulocytes > or = 0.6 per cent were the most frequent factors associated with PNH clone found in all PNH subjects, but only in 28.6 per cent and 14.3 per cent respectively, of non-PNH subjects. Mortality rate was higher in non-PNH subjects (28.5 per cent) compared to 25 per cent of PNH subjects. We conclude that immunohistochemical staining of bone marrow sections is a sensitive tool to detect the emergence of PNH clone in aplastic anemia patients. Thrombotic complications should be anticipated in cases with aplastic anemia having a PNH clone.

Anemia, Aplastic↗
PubMed1996

First report of a B cell lymphoproliferative disorder arising in a patient treated with immune suppressants for severe aplastic anemia.

Aplastic anemia is a disorder characterized by pancytopenia and bone marrow hypocellularity. There is some evidence that aplastic anemia may be due to suppression of hematopoiesis by activated T-suppressor cells. Thus, immunosuppressive agents have been used as an alternative to bone marrow transplantation for treatment. We report on a unique case of a patient with aplastic anemia who was treated with a course of immunosuppression including cyclosporine (CSA), anti-thymocyte globulin (ATG), and prednisone. Five months after this treatment, the patient developed a B cell lymphoproliferative disorder which was successfully treated with radiation therapy. Prior reports of CSA-associated lymphoproliferative disorders have appeared in the literature as potential side effects of immunosuppression following transplantation. This is the first report of a lymphoproliferative disorder associated with immunosuppressive treatment of aplastic anemia in a nontransplant setting. Thus, when presenting options for treatment of aplastic anemia, lymphoproliferative disorders should be included as a rare complication of immunosuppressive therapy.

Adolescent↗
PubMedDate not supplied

Aplastic anemia.

Aplastic anemia is a disease that presents with a hypocellular marrow and peripheral blood pancytopenia. In Europe and the United States, it has an age-adjusted incidence per million population per year of 2.2 compared to 11.0 in Japan and Korea. Pathogenic mechanisms are varied and include intrinsic defects of hematopoietic stem cells, defects in the marrow microenvironment, and abnormal humoral or cellular immune control of hematopoiesis. In most patients, aplastic anemia is of unknown etiology, whereas in some, the disease can be related to infections, drugs and chemicals, and hereditary causes. Therapy for aplastic anemia includes blood component transfusions, antibiotics, androgenic steroids, and corticosteroids. With supportive care, most patients with aplastic anemia die within a year of diagnosis, and only approximately 20% of patients are surviving, although often with persisting hematologic abnormalities. The use of hematopoietic growth factors has shown, for the most part, only transient beneficial effects. More definitive therapy has been the use of immunosuppressive agents including antithymocyte globulin, cyclosporine, and cyclophosphamide. With immunosuppressive therapy, a variable proportion of patients respond to therapy, ranging from 20% to 80%. However, although responses may be frequent, long-term outlook is guarded because some patients may relapse with aplastic anemia, whereas others may go on to have a clonal disorder develop, including myelodysplasia, leukemia, or paroxysmal nocturnal hemoglobinuria. As a result, survival estimates at 15 to 18 years may be only on the order of 30%. More definitive therapy has been with transplants of hematopoietic stem cells from allogeneic donors. Transplants are carried out after high-dose immunosuppressive conditioning programs. Best current results show long-term, event-free survivals with successful allografts on the order of 90%.

Anemia, Aplastic↗
PubMed2000

TT virus infection in Thailand: prevalence in blood donors and patients with aplastic anemia.

Aplastic anemia has been reported to occur after viral hepatitis of unknown etiology. Recently, TT virus (TTV), a novel DNA virus, was identified in a Japanese patient with posttransfusion non-A-E hepatitis. The prevalence of TTV infection was investigated among blood donors and patients with aplastic anemia in Thailand. Of 99 blood samples from blood donors, 37 tested positive for TTV DNA via semi-nested polymerase chain reaction (PCR) using TTV-specific primers. Seventeen percent of samples from blood donors younger than 20 were positive for TTV DNA, whereas 48% from donors older than 20 were positive. The high prevalence of TTV infection in Thailand is comparable to that reported in China (28%), Mongolia (43%), and Egypt (29%). Forty-two percent of newly diagnosed aplastic anemia patients tested also had TTV DNA in blood. The detection rate of TTV DNA in aplastic anemia patients does not differ significantly from rates in normal blood donors. Our present data thus argue against the role of this novel hepatitis-associated virus in the pathogenesis of aplastic anemia in Thailand. However, larger epidemiological studies may be needed to further evaluate their association.

Adult↗
PubMed2005

Human parvovirus B19 in patients with aplastic anemia.

Aplastic anemia is characterized by pancytopenia with hypoplastic bone marrow. Various factors including viral infections have been implicated as the precipitating factors. Human parvovirus B19 has been associated with red-cell aplasia, leukopenia, and thrombocytopenia. The present study was carried out to determine the role of parvovirus B19 in aplastic anemia patients. Twenty-seven aplastic anemia patients and 20 healthy controls were tested for the presence of parvovirus B19 infection by detecting parvovirus B19-specific IgM by ELISA and viral DNA by PCR. Parvovirus B19 IgM and viral DNA were detected in significantly higher numbers of patients in comparison to the controls (40.7% vs. 5%, P < 0.01; 37% vs. 0%, P < 0.001, respectively). The presence of parvovirus DNA in aplastic anemia patients indicates active or recent infection. However, more studies are needed to explore the mechanism of bone-marrow aplasia due to human parvovirus B19 infection.

Adolescent↗
PubMed1985

Current considerations of the etiology of aplastic anemia.

Aplastic anemia is a disorder characterized by marrow aplasia and pancytopenia. The pathogenetic mechanisms that lead to bone marrow aplasia have been intensively studied. Data obtained from these studies suggest that aplastic anemia is a heterogeneous disorder with regards to pathogenesis. Bone marrow aplasia may result from a number of abnormalities including qualitative or quantitative abnormalities of hematopoietic stem cells, abnormal interaction between bone marrow accessory cells (lymphocytes and macrophages) and hematopoietic stem cells, cytotoxic humoral inhibitors of hematopoiesis, and abnormalities of the bone marrow microenvironment. A number of new therapeutic options have improved the survival of patients with aplastic anemia. Allogeneic bone marrow transplantation has actually resulted in the cure of patients. Unfortunately, only a minority of patients have a suitable bone marrow donor and alternate modes of therapy have been sought. Encouraging results have been reported from several centers concerning the use of antilymphocyte serum in patients with aplastic anemia. Certainty of the ultimate long-term benefit of this type of immunosuppressive therapy is not possible until careful, randomized, prospective studies of its use are completed.

Age Factors↗
PubMed1997

Practical aspects in the diagnosis and management of aplastic anemia.

Aplastic anemia may result from several pathogenic mechanisms, the most common is idiopathic. The current definitive treatments for aplastic anemia are bone marrow transplantation (BMT) or immunosuppressive (IS) therapy. The benefits of each are comparable. However, certain subsets of patients derive superior benefit from one or the other. Bone marrow transplantation is the initial treatment of choice for young patients (< 20 years old). It results in the complete reconstitution of hematopoiesis, whereas autologous hematopoietic remissions after IS therapy are more susceptible to relapse. Survival rates after BMT, in patients between the ages of 20 and 40, are comparable to those reported for IS therapy. Better survival rates after BMT have been achieved with improved conditioning regimens and graft-versus-host disease prophylaxis. For patients older than 40, the treatment of choice is IS. Long-term complications of IS therapy include recurrence and development of clonal myeloid disorders. Long-term complications after BMT include graft-versus-host disease and secondary neoplasms. The IS regimen includes the combination of antithymocyte globulin and cyclosporin A. The addition of growth factor to the IS regimen seems promising; however, their use on their own is not recommended. Androgens have been shown to be inferior in the treatment of aplastic anemia. The role of BMT from an unrelated donor is being investigated.

Anemia, Aplastic↗
PubMed2002

[Case of acute deep neck infection in a patient with aplastic anemia].

Aplastic anemia often causes a life-threatening infection. We report a case of deep neck infection in a 30-year-old man with aplastic anemia treated with intensive antibiotics after admission, who rapidly recovered without surgery. The infection was caused by dental caries with an immunocompromised host via hemodyscrasia. He remains free from inflammation recurrence 5 months after treatment. We discuss the importance of early, appropriate treatment of deep neck infection associated with aplastic anemia occurring in immunocompromised patients.

Acute Disease↗
PubMed2006

Current concepts in the pathophysiology and treatment of aplastic anemia.

Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the benefits of transplantation to patients who are older or who lack family donors. Recent results with alternative sources of stem cells and a variety of conditioning regimens to achieve their engraftment have been promising, with survival in small pediatric case series rivaling conventional transplantation results.

Anemia, Aplastic↗
PubMed2005

The use of mycophenolate mofetil in treating patients with non responding aplastic anemia.

Aplastic anemia is a relatively uncommon disease and conventional management options include immunosuppressive drugs and/or haematopoeitic stem cell transplantation. It is now known that the pathogenesis of aplastic anemia is immune mediated. Mycophenolate mofetil is a common immunosuppressive drug now used mainly in prophylaxis of graft rejection in organ transplant and also for prevention/treatment for graft versus host disease in haemtopoeitic stem cell transplantation. It is thought that mycophenolate mofetil may be useful in this group of patients. In this short report, mycophenolate mofetil was tried in 6 patients who had severe aplastic anemia with variable doses for a minimum duration of 9 months. The result has however not been encouraging.

Adult↗
PubMed2006

Trisomy 1q in a patient with severe aplastic anemia.

Aplastic anemia is a rare, serious disease characterized by hypocellular bone marrow and pancytopenia in the peripheral blood. Most cases are acquired, idiopathic, and without gross cytogenetic abnormalities. A few chromosome abnormalities have recurred among a small subset of patients, most commonly trisomy 8 and monosomy 7. Some of these chromosome abnormalities have prognostic and therapeutic significance, although for most the clinical relevance is not known. We present the case of a 40-year-old man with idiopathic severe aplastic anemia in bone marrow cells with trisomy of the whole long arm of chromosome 1 due to an unbalanced translocation between chromosomes 1 and 15 at breakpoints of q10 and 15q10. This clonal abnormality (which, to our knowledge, has not been previously reported in a patient with aplastic anemia) suggests that genes on 1q may be involved in marrow aplasia.

Adult↗
PubMed1995

Posttransfusional, LKM-1-autoantibody-positive hepatitis C virus infection, cryoglobulinemia, and aplastic anemia.

Aplastic anemia is occasionally caused by viral hepatitis, hepatitis C virus being the most important factor. Pathogenetically, decreased bone marrow function, abnormalities of the bone marrow microenvironment, and immune-mediated suppression of hematopoiesis are important. Hepatitis C virus infection is associated with a variety of extrahepatic manifestations including autoimmune features like cryoglobulinemia, Sjögren's syndrome, and autoimmune hepatitis. Here we report the case of a 42-year-old man with aplastic anemia due to posttransfusional hepatitis C virus infection associated with cryoglobulinemia and LKM-1 autoantibodies. Following a triple immunosuppressive therapy, there was a complete reconstitution of the bone marrow. Serum HCV-RNA as well as plus- and minus-stranded HCV-RNA in peripheral blood mononuclear cells (PBMC) were detected before immunosuppressive therapy. After therapy, serum HCV-RNA persisted. Furthermore, PBMC now were positive for plus-stranded RNA only. However, in bone marrow-derived precursor cells we failed to demonstrate HCV molecules after therapy. This would argue for reconstituted PBMC from newly generated uninfected precursor cells. It remains unclear as to whether the autoimmune character of the disease or the hepatitis C virus infection itself have contributed to the pathogenesis of the aplastic anemia.

Adult↗
PubMed2003

Ex vivo immunotherapy for patients with benzene-induced aplastic anemia.

Aplastic anemia is a bone marrow failure disorder characterized by pancytopenia and a hypocellular marrow. Benzene is one of the etiologic agents capable of inducing the disease. With modest to severe aplastic anemia, one previously untreated patient and 13 patients who had failed immunosuppressive therapy were studied. Peripheral blood mononuclear cells from patients were expanded in vitro with a combination of cytokines and a calcium-mobilizing agents for 2 days, and the activated cells were infused intravenously once a week. In some cases, we used allogenic leukocytes instead of autologous cultured lymphocytes. After 6-35 weeks of the treatment, all patients had multilineage responses to this therapy and achieved complete disease remission, defined as normal blood count, independence from transfusion, and normal bone marrow histology. The therapy was safe and well tolerated with minimal side effects. The cultured cells produced interleukin-1 and induced immune responses in vivo. Serum interleukin-2 and interferon- gamma were detected following cell infusion. Finally, patients had sustained responses to the therapy and no relapse was found up to 18 months after cellular therapy.

Adult↗
PubMed1990

Intravenous immunoglobulin in the treatment of aplastic anemia.

Aplastic anemia is characterized by reduced production of mature erythrocytes, granulocytes, and platelets from marrow stem cells leading to peripheral blood pancytopenia. In many cases, it appears that there is an aberrant immune response suppressing stem cell differentiation and renewal, leading to bone marrow aplasia and the observed peripheral blood pancytopenia. This report describes a patient with aplastic anemia unresponsive to antithymocyte globulin and high-dose steroid therapy who did respond to intravenous immunoglobulin and now has normal peripheral blood counts.

Adrenal Cortex Hormones↗
PubMed2006

Pathophysiologic mechanisms in acquired aplastic anemia.

Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Absence of hematopoietic cells has been recognized from the characteristic morphology for a century; an immune pathophysiology has been inferred from improvement in blood counts with immunosuppressive therapy in the majority of patients. Molecular mechanisms underlying both T cell effector cells and the target marrow stem and progenitor cells are now being identified. Activated type 1 cytotoxic T cells and type 1 cytokines have been implicated in cell culture experiments; clues to the molecular basis of the aberrant immune response include cytokine gene polymorphisms and abnormalities in the regulatory pathways for gamma-interferon. For stem cell depletion, mutations in genes of the telomere repair complex are present in some patients with apparently acquired aplastic anemia. Telomerase deficiency is associated with short telomeres and a quantitative reduction in marrow progenitors and likely also a qualitative deficiency in the repair capacity of hematopoietic tissue.

Anemia, Aplastic↗
PubMed1992

In vitro revelations of aplastic anemia.

Aplastic anemia (AA) is a most difficult disease to study in vitro. By the time the disease presents, the marrow is already hypocellular and the peripheral blood shows pancytopenia, leaving little material remaining for study. However, an understanding of its pathogenesis could provide insight into the control of normal hemopoiesis since AA is an in vivo manifestation of failure of normal hemopoiesis and may provide a way of examining stromal cell-stem cell relationships. Recent interest in the pathogenesis of AA has resulted from a) new laboratory techniques, such as stem cell purification used with modifications of the long-term bone marrow culture system and analysis of stem cells at the molecular level with X-linked DNA probes, and b) the availability of recombinant human hemopoietic growth factors (HGF) in large quantities. Consequently, analyses of the function of some of the individual components of stromal cell mediated hemopoiesis in AA patients have been performed. This has been paralleled, and in some instances preceded, by clinical trials of HGF in patients with AA.

Anemia, Aplastic↗
PubMed1997

T-cell receptor beta chain variability in bone marrow and peripheral blood in severe acquired aplastic anemia.

Aplastic anemia (AA) is characterized by multilineage bone marrow failure of unknown etiology. In order to assess the role of immune-mediated mechanisms in hematopoietic suppression, we examined the diversity of T lymphocyte repertoire in terms of variable (V) gene segment usage of the T cell receptor (TCR) beta chain in bone marrow and peripheral blood of six patients with severe untreated AA. Expression of transcripts encoding Vbeta1-Vbeta24 subfamilies was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The results revealed that T lymphocytes in AA utilize highly diverse segments of the beta chain loci. Over the heterogenous Vbeta expression background, transcripts encoding Vbeta3, Vbeta20, Vbeta21, and Vbeta22 subfamilies were enhanced by at least threefold in 5 of 6 patients as compared to normal samples, but a different transcript species was over expressed in each patient. To evaluate clonality of T cells, size diversity within the complementarity determining region 3 (CDR3) and usage of TCRbeta joining (J) gene segments were analyzed in PCR products specific for each of the 24 Vbeta subfamilies. We found that the majority of transcripts display normal CDR3 size patterns, as is characteristic of polyclonal populations. Nevertheless, one or two predominating junctional rearrangements were observed in each patient. They were identified in Vbeta5, Vbeta7, Vbeta8, Vbeta13, Vbeta15, Vbeta16, and Vbeta23 transcripts, which differed from patient to patient and did not correspond to transcripts with an abnormally high expression level. Our results demonstrate that T cell repertoire in AA is random with respect to the TCR beta chain. Unique rearrangements detected in the CDR3 region are suggestive of a limited process of an antigen-driven (oligo)clonal T cell expansion which may take place over the overwhelmingly polyclonal repertoire of T lymphocytes at the onset of severe AA.

Adult↗