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JURNAL ANEMIA APLASTIK PDF

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Keywords aplastic anemia, chloramphenicol, mice, shrimps. Pengaruh residu khloramfenikol dalam udang windu terhadap kejadian anemia aplastik pada. Sari Pediatri, Vol. 7, No. 1, Juni Judul: Masalah pada Tata Laksana Anemia Aplastik. Background: Aplastic anemia is a well-recognized form of marrow failure. The incidence of aplastic anemia is subjected to wide variation.

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Most acquired aplastic anemia AA is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and an empty bone marrow, which can be successfully treated with either immunosuppressive therapy IST or hematopoietic stem-cell transplantation HSCT. In AA, oligoclonally expanded cytotoxic T-cells induce apoptosis of hematopoietic progenitors.

Regulatory T-cells are significantly reduced in patients’ peripheral blood and in an AA murine model, infusion of regulatory T-cells ameliorates disease progression. In a minority of cases, loss-of-function mutations in telomerase complex genes may underlie disease development. Long term survival, once strongly linked to response to immunosuppressive therapy, can now be achieved even among non-responders due to significant advances in supportive care and better salvage treatments.

Evidence juenal accumulated in the recent years further corroborating an immune-mediated process underlying AA pathogenesis. HSCT from a matched ajemia donor is preferred for children and young adults with severe AA, and IST is employed when HSCT is not feasible due to age, lack of a histocompatible sibling, co-morbidities, or by patient choice. In its severe form, aplastic anemia AA is a life-threatening bone marrow failure disorder which, if untreated, is associated with very high mortality.

Hematopoietic stem cell transplantation HSCT offers an opportunity for cure, but most patients are not suitable candidates for this procedure due to advanced age, comorbidities, or lack of a histocompatible donor. For these patients, comparable long term survival is attainable with immunosuppressive treatment IST with anti-thymocyte globulin ATG and cyclosporine CsA. Kurnal several etiopathogenic triggers have been proposed in AA, the majority of cases are idiopathic, with a small percentage of cases occurring after an episode of seronegative hepatitis.

Acquired AA is a rare disease; almost half of cases occur during the first three decades of life. The incidence in Western countries is two cases per million per year and about fold higher in Asia [ 1 — 3 ].

Benzene and pesticides, while epidemiologically associated, account for a small etiologic fraction. In rural Thailand, associated exposures to non-bottled water, as well as to certain animals, to animal fertilizer, and also to pesticides suggest an infectious etiology [ 2 ]. The rarity of acquired AA most probably is accounted for by a combination of infrequent exposure events, a diversity of host genetic predisposing factors, and individual differences in the immune response.

During the last century, AA was attributed to an idiosyncratic reaction to drug or chemical exposure. The association of medical drug use to AA is of great importance, as it is devastating to patients and physicians and presents serious legal consequences and problems in pharmaceutical drug development [ 4 ]. However, the study of idiosyncratic drug reactions, by definition extremely rare, is difficult and the only clear predisposition to abnormal drug metabolism underlying susceptibility is one study of a single individual exposed to carbamazepine published over 20 years ago [ 5 ].

Overrepresentation of drug metabolizing glutathione-S-transferase gene deletions have been observed in some series [ 67 ] but no reasonable mechanism has been developed for chloramphenicol. Pregnancy and eosinophilic fasciitis are linked to AA.

Jurnal Anemia Aplastik | inamedina

Five to ten percent of cases of AA follow an episode of seronegative hepatitis [ 8 ], but despite intensive efforts, an infectious agent has not been identified. In most cases, AA behaves as an immune-mediated disease. An immune response dominated by oligoclonal expanded cytotoxic T-cells targets hematopoietic stem and progenitor cells, inducing their death via apoptosis and hematopoietic failure.

Recovery of autologous hematopoiesis in patients who failed to engraft after stem cell transplant and responsiveness to immunosuppressive therapies are the major clinical evidences supporting an immune pathophysiology underlying acquired AA. Removal of lymphocytes from aplastic bone marrows improves colony numbers in tissue culture, and their addition to normal marrow inhibited hematopoiesis in jurnaal [ 9 ]. Regulatory T cells, which control and suppress auto-reactive T cells, are decreased at presentation in almost all patients with AA [ 13 ].

In a mouse model of immune-mediated marrow failure, addition of T regulatory cells abrogated pancytopenia induced by the infusion of lymph node cells [ 14 ].

Why T-cells are activated in AA is unclear. HLA-DR2 is over-represented among patients, suggesting a role for antigen recognition, and its presence aplsstik predictive of a better response to cyclosporine [ 1516 ].

These alterations in nucleotide sequence and in gene regulation suggest a genetic basis for aberrant T cell activation in bone marrow failure.

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Immune attack leads to marrow failure. The reduced number and function of the marrow is secondary to cell destruction, and apoptosis is prevalent among the few remaining elements [ 20 — 22 ]. A minority of AA cases may share pathophysiologic basis with inherited marrow failure syndromes. One peculiar feature of white blood cells in AA is short telomeres, observed in approximately a third of cases [ 2425 ].

Although initially blamed on excessive stem cell turnover, telomere shortening in some cases of acquired AA and in dyskeratosis congenita, a constitutional marrow failure syndrome is due to mutations in components of the telomerase complex, causing low telomerase activity, progressive telomere erosion, and a deficient proliferative capacity of hematopoietic stem cells [ 26 — 29 ].

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The mechanisms linking immune-mediated and pre-malignant or malignant pathophysiologies are not well elucidated in marrow failure or in other human autoimmune diseases that predispose to cancer.

The global absence of large number of cell surface proteins in PNH has been hypothesized to allow escape and survival of a pre-existing mutant clone. Aneuploidy develops in a minority of patients treated with immunosuppression over time, usually monosomy 7 and trisomy 8[ 32 ]. AA patients who develop trisomy 8 usually respond to IST [ 33 ].

T-cell oligoclones appear to recognize the aneuploid cells and specifically WT1 as an antigen, but target cells are not killed due to their expression of anti-apoptotic genes [ 34 ]. Monosomy 7 is the most frequent cytogenetic abnormality in evolving AA; it confers a poor prognosis: Monosomy 7 has been linked to exogenous use of G-CSF in AA [ 3637 ] and laboratory studies suggest that aneuploid clones expand in an abnormal cytokine milieu rich in G-CSF due to the presence of a short G-CSF receptor isoform, which signals proliferation but not amemia [ 38 ].

The presence of even small monosomy 7 clones in the bone marrow, as detected by FISH but not by routine cytogeneticsis a poor prognostic indicator for response to IST [ 39 ]. While it is generally believed that h-ATG administration leads to depletion of immune competent cells, its exact mechanism of action remains unclear [ 40 ]. H-ATG preparations contain a variety of antibodies recognizing human T-cell epitopes, many directed against activated T-cells or activation antigens [ 4142 jufnal.

In contrast to ATG, CsA has a more selective inhibitory effect on T lymphocytes, suppressing early cellular response to antigenic and regulatory stimuli. The benefits and limitations of this regimen as initial therapy have been quantitated in systematic studies in the US, Japan and Europe: The majority of responses to IST are not complete, notwithstanding, hematologic response almost always equates to cessation of transfusion, and multiple studies have shown a strong correlation between hematologic response and long term survival [ 4549 ].

Both refractory and relapsed patients are frequently treated with further courses of ATG. R-ATG is similar to h-ATG except that gamma immune globulin is obtained by immunization of rabbits with appastik thymocytes.

Clinically, r-ATG appears to be more immunosuppressive as a more prolonged lymphopenia is observed with this agent compared to h-ATG [ 52 ]. This enhanced lymphocytotoxicity of r-ATG may be explained by higher affinity IgG subtype to human lymphocytes, less batch-to-batch variability, longer half-life, and more efficient lymphocyte depletion [ 53 ].

For relapsed patients, re-introduction of CsA commonly result in improvement in blood counts, however, CsA-dependence is frequent and the dose of CsA usually is tapered slowly with hematologic monitoring [ 45 ]. However, we have noted a striking improvement in survival among non-responders to initial h-ATG treated at our institution in recent years [ 59 ].

Retrospective analysis has shown that the decrease in deaths in refractory patients is most likely due to more successful salvage therapies repeat IST and HSCT as well as better supportive care, mainly the introduction of better antifungal drugs. Proposed criteria to date have been complex or relied juenal non-standardized tests. A recent reported Japanese randomized study suggested that the addition of G-CSF might reduce the incidence of relapse [ 65 ], but this results was not observed in other studies of similar design [ 66 ].

In moderate AA, the clinical course is variable: Very few clinical trials have specifically addressed moderate disease. Immunosuppression can reverse moderate pancytopenia and alleviate transfusion requirements; ATG and cyclosporine are more effective in combination [ 68 ].

Daclizumab, a humanized monoclonal antibody to the jrunal receptor, improved blood counts and relieved transfusion requirements in 6 of 16 evaluable patients; the outpatient regimen had little toxicity [ 69 anemi. Allogeneic bone marrow transplantation from a histocompatible matched sibling is curative therapy in the majority of SAA patients who undergo this procedure.

Chronic GVHD has been a major cause of morbidity and mortality in patients who survived more than 2 years post graft, with the necessity of long term immunosuppressive therapy common [ 72 ]. Graft rejection, a historic problem in the application of transplant to SAA is now infrequent, likely a benefit of less immunogenic blood products leukocyte-depleted erythrocytes, for aplastiik from fewer donors platelets collected by cytoapheresis [ 7374 ].

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Also, better radiation-free conditioning regimens have improved the tolerability of HSCT and allowed for engraftment in heavily transfused and in some cases alloimmunized patients who were refractory to IST [ 7576 ]. In a retrospective analysis, the use of PB progenitor cell graft has been correlated to a worse outcome and anemix chronic GVHD in younger patients less than 20 compared to those who receive a bone marrow graft in HLA-matched sibling donor transplants [ 78 ].

This difference was not observed in older patients. As the outcome in aplastic patients who have failed a single round of ATG has been poor, alternative sources of hematopoietic stem cells have been sought, anemoa from now very large donor registries. Older patients with poor performance status have the worst outcome and better results are obtained in children than for adults. Progress in donor selection through high-resolution HLA typing technology has likely contributed to decreased graft rejection and better survival [ 82 ] and recently reported outcomes for MUD rival those for an HLA-matched sibling transplant in children and young adults [ 8384 ].

APLASTIC ANEMIA

The optimal conditioning regimen for a MUD HSCT remains uncertain; in contrast to allogeneic jurjal transplants, transplants from unrelated donors still require low dose irradiation cGy to ensure engraftment, with attendant long-term complications [ 8586 ].

In general, prospective trials have enrolled fewer patients jurnla have better results, albeit with short periods of post-transplant observation [ 71 ].

Those who underwent a MUD HSCT had a higher failure free survival defined as survival with response compared to those who underwent a second course of IST, although no difference in overall survival was observed between the 2 groups [ 87 ]. In recent years, further evidence has accumulated to anema the hypothesis that bone marrow failure in Jrunal results from immunologic destruction of hematopoietic stem and progenitor cells.

Current research is aimed at investigating the mechanisms that lead to T cell activation and, whether it is antigen driven or a result of immunological disarray. The clinical implication of telomere shortening in AA is being investigated for prognostic significance. Most patients with AA are now expected to survive regardless of the treatment modality employed.

National Center aplaztik Biotechnology InformationU. Author aplasyik available in PMC Aug 2. YoungPhillip Scheinbergand Rodrigo T. Author information Copyright and License information Disclaimer. The publisher’s final edited version of this article is available at Curr Opin Hematol. See other articles in PMC that cite the published article. Abstract Purpose of review Most acquired aplastic anemia AA is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and an empty bone marrow, which can be successfully treated with either immunosuppressive therapy IST or hematopoietic stem-cell transplantation HSCT.

Recent findings In AA, oligoclonally expanded cytotoxic T-cells induce apoptosis of hematopoietic progenitors. Summary Evidence has accumulated in the recent years further corroborating an immune-mediated process underlying Aplaxtik pathogenesis.

Introduction In its severe form, aplastic anemia AA is a life-threatening bone marrow failure disorder which, if untreated, is associated with very high mortality. Epidemiology and Anfmia Acquired AA is a rare disease; almost half of cases occur during the first three decades of life. Pathophysiology In most cases, AA behaves as an immune-mediated disease.

T-cell-mediated destruction of the bone marrow Recovery of autologous hematopoiesis in patients who failed to engraft after stem cell transplant and responsiveness to immunosuppressive therapies are the major clinical evidences supporting an immune pathophysiology underlying acquired AA.

Hematopoiesis Immune attack leads to marrow failure. MDS Aneuploidy develops in a minority of patients treated with immunosuppression over time, usually monosomy 7 and trisomy 8[ 32 ]. Allogeneic Hematopoietic Stem Cell Transplantation HLA-matched sibling donor transplant Allogeneic bone marrow transplantation from a histocompatible matched sibling is curative therapy in the majority of SAA patients who jkrnal this procedure.

Conclusion In recent years, further evidence has accumulated to strengthen the hypothesis that bone marrow failure in AA results from immunologic destruction of hematopoietic stem and progenitor cells. Incidence of aplastic anemia and agranulocytosis in Latin America: Appastik Paulo Medical Journal.

Aplastic Anemia, Acquired and Inherited. Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking GSTT1 gene.