Prognosis Of Aplastic Anemia Research Articles

Interleukin-10 promoter variability is associated with the susceptibility, severity, and clinical outcomes of aplasitc anemia in Han-Chinese population.

Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST. In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)-10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA. We observed that CT genotype of IL-10 rs1800896 was associated with a decreased risk of AA (adjusted OR=0.541 [95% CI 0.295-0.993], p=.047). Besides, the disease severity differed considerably by IL-10 gene promoter genotypes and alleles. Furthermore, IL-10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR=0.409 [95% CI 0.178-0.943, p=.036] for rs1800871 and GG + GT vs. TT, adjusted OR=0.396 [95% CI 0.173-0.909, p=.028] for rs1800872, respectively). The polymorphisms of IL-10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens.

Interlukin-27 rs153109 polymorphism confers the susceptibility and prognosis of aplastic anemia in Chinese population.

Accumulating evidence has indicated that interleukin (IL)-27 and its gene polymorphisms exert pivotal impact on several autoimmune disorders. This research intended to investigate the relationship between IL-27 rs153109 polymorphism with risk and prognosis for aplastic anemia. IL-27 rs153109 polymorphism was detected with polymerase chain reaction-ligase detection reaction in 238 patients with aplastic anemia and 215 normal individuals. Enzyme-linked immunosorbent assays were applied to measure the plasma level of IL-27. Frequencies of rs153109 AA and GG genotype were statistically higher in aplastic anemia patients compared to controls. Similar results were observed when further divided patients into nonsevere and severe ones. That means carriers of AA and GG genotype are accompanied by an increased risk of developing aplastic anemia. Plasma IL-27 levels of aplastic anemia patients were remarkably elevated than normal group and had positive relation with disease severity. Furthermore, patients with AA genotype had obviously higher IL-27 levels than ones with AG and GG genotype. Moreover, patients carrying AA genotype exhibited a poorer reaction to immunosuppressive therapy and were more prone to clonal evolution. IL-27 rs153109 polymorphism confers genetic predisposition to aplastic anemia and influences disease prognosis, potentially by regulating IL-27 expression, which help broaden potential pathogenesis of aplastic anemia. Specifically, for patients with AA genotype, more aggressive therapeutic strategies such as hematopoietic stem cells transplantation are warranted.

A single-center study of serum sickness caused by rabbit antithymosinglobulin therapy in children with acquired aplastic anemia

Objective To investigate the related factors of the serum sickness morbidity in the treatment of children with acquired aplastic anemia (AA) by rabbit antithymosinglobulin (ATG), summarize the clinical characte-ristics of serum sickness and evaluate the influence of serum sickness on the prognosis of AA. Methods The data of patients diagnosed as AA after treated with immunosuppressive therapy (IST) in Beijing Children′s Hospital, Capital Medical University, from March 2016 to December 2018 were collected, and the onset time, clinical manifestations, treatment, and prognosis of serum sickness were analyzed. Results A total of 48 cases were enrolled, with the median age of 5 years and 5 months (ranging from 2 years and 1 month to 15 years and 6 months), and the proportion of male to female was 1.4∶1.0, 75.0% of the patients(36/48 cases) developed serum sickness.The median onset time was the 11th day and 72.2% of the patients (26/48 cases) occurred from the 7th to the 14th day during IST.The 3 main clinical manifestations included arthralgia (63.9%, 23 cases), fever (52.7%, 19 cases) and rash (52.7%, 19 cases). There was no significant difference in peripheral blood leukocytes, neutrophils and lymphocytes between the patients with serum sickness and patients without serum sickness before IST and during serum sickness (all P>0.05). The incidence of serum sickness in children who received continuous glucocorticoid prophylaxis after IST (2/12 cases, 16.6%) was lower than that of those who did not (34/36 cases, 94.4%), and the difference was significant (χ2=29.037, P 0.05). Conclusion Children with AA are prone to develop serum sickness after IST treatment.The peak period of incidence of serum sickness is the second week during IST, and the main clinical manifestations of serum sickness include arthralgia, fever, and rash.There is no correlation between the incidence of serum sickness and the blood routine test before IST and during serum sickness.The incidence of serum sickness can be reduced by giving glucocorticoid prophylaxis, and glucocorticoid is still effective after the onset of the serum sickness.There is no correlation between the morbidity of serum sickness and the prognosis of AA treated with IST. Key words: Child; Aplastic anemia; Immunosuppressive therapy; Serum sickness

Analysis of Correlation of Immune T Cell Subsets, TNF-α, IFN-γ and sFas levels with Severity and Prognosis in Aplastic Anemia Patients

To explore the correlation of immune T cell subsets and expression levels of TNF-α, IFN-γ and sFas with the severity and prognosis of aplastic anemia(AA) patients. Ninety-five patients with aplastic anemia treated in our hospital were selected and enrolled in AA group, 43 cases of which were included in the acute group and 52 cases in the chronic group according to the disease status of patient's. Then, 50 cases of healthy volunteers in the same period were enrolled in the control group, and the changes of immune T cell subsets, and sFas serum TNF-α, IFN-γ and levels of the 3 groups were compared. The ROC curve was used to analyze the value of each index for evaluating the severity of the disease, 95 patients with aplastic anemia were followed up and the Kaplan-Miere survival curve was used to analyze the effect of different index levels on the progression-free survival of the patients. the serum level of CD4+ level and CD4+ /CD8+ ratio in AA group were significantly lower than those in the control group (P<0.05), and the CD8+ level in AA group was significantly higher than that in the control group (P<0.05). The CD4+ level and CD4+ /CD8+ ratio in the acute group was significantly lower than those in the chronic group (P<0.05), and the CD8+ level in the acute group was significantly higher than that in the chronic group (P<0.05). The serum level of TNF-α and IFN-γ of the patients in AA group was significantly higher than those in the control group (P<0.05), and the level of sFas in AA group was significantly lower than those in the control group (P<0.05). The levels of serum TNF-α and IFN-γ in the acute group were significantly higher than that in the chronic group (P<0.05), and the level of sFas was significantly lower than that in the chronic group (P<0.05). The analysis of each index value for predicting the severity of AA by ROC showed that the area under curve of CD4+ /CD8+ , TNF-α, IFN-γ and sFas for predicting the patients' condition was 0.954, 0.763, 0.853 and 0.857, respectively. Kaplan-Miere survival curve analysis showed that CD4+ /CD8+ ratio had a significant effect on progression-free survival (P<0.05), the TNF-α, IFN-γ and sFas levels had no significant effect on progression-free survival (P>0.05). The patients with aplastic anemia have significantly abnormal T lymphocyte subsets, there is a certain correlation between the serum TNF-α, IFN-γ and sFas levels with aplastic anemia, each index can reflect the disease severity, and the changes of T lymphocyte subsets has important influence on the clinical prognosis of the patients.

Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia.

To gain insight into the origin and clinical significance of leukocytes that lack human leukocyte antigen A (HLA-A) allele expression caused by a copy-number-neutral loss of heterozygosity in the short arm of chromosome 6 in patients with acquired aplastic anemia (AA),weused a high-sensitivity flow cytometry assay to investigate the presence of HLA-A allele-lacking leukocytes(HLA-LLs) in 144 AA patients. HLA-LLs, accounting for0.2-99.8% of each leukocyte population, were detected in 18 of 71 (25.4%) newly diagnosed patientsand in 25 of 73 (34.2%) previously treated patients. The lineage combination patterns of the HLA-LLs in the 43 HLA-LL(+)patients were granulocytes (Gs), monocytes (Ms), Bcells (Bs), and Tcells (Ts; GMBT) in 13 cases, GMB in 16 cases, GM in 11 cases, and B alone in three cases. The response rate to antithymocyte globulin plus cyclosporine therapy (100%) and the 2-year, failure-free survivalrate (100%) in 8 newly diagnosed HLA-LL(+) patients were significantly higher than in 23 HLA-LL(-) patients (52.2% for both). These data suggest that HLA-LLs are a useful marker of the presence of immune pathophysiology in AA and that T-cell attacks against hematopoietic progenitor cells, rather than against hematopoietic stem cells, can trigger bone marrow failure in AA patients.

The clinical relevance and prognostic significance of microsomal epoxide hydrolase gene polymorphisms and their susceptibility to acquired aplastic anemia: an Egyptian study

Background: Microsomal epoxide hydrolase enzyme (mEPHX) is involved in xenobiotics detoxification. Two variants of mEPHX, Tyr113His and His139Arg, have been described. Both may lead to acquired aplastic anemia (AA).Objectives: Assessing mEPHX genetic polymorphisms and detecting their impact on susceptibility and prognosis in Egyptian AA patients.Participants and methods: mEPHX 113 and 139 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 patients with AA and 100 control subjects.Results: Both mEPHX Tyr113His and His139Arg gene polymorphisms were associated with increased risk of developing AA, and have a significant impact of bad prognosis (p value < 0.01).Conclusions: These mEPHX gene polymorphisms can be considered as risk factors and predictive molecular markers for prognosis in AA patients.

Aplastic Anemia in Egypt: Current Situation and Future Prospective

Aplastic anemia (AA) is a hypoproliferative anemia that led to a significant morbidity and mortality. Recently, dramatic improvement in prognosis of AA was achieved; this was in part due to advances in immunosuppressive therapy and HSCT. Nevertheless, AA is still one of the most challenging hematological disorders that could face a hematologist. This study was conducted at Assiut University Hospital (AUH), Assiut, Egypt to evaluate current situation and future prospective of AA. 63 patients with AA were prospectively enrolled in the study; they were admitted at the Hematology unit, AUH in the period 1stJan2011 to Feb2012, a 38 patients with iron deficiency anemia (IDA) were included for comparison. Patients' demographic and clinical data were collected through medical history and clinical examination. Both direct and indirect health care costs of anemia were assessed Direct parameters included doctors' and hospital fees, costs of laboratory investigations, medication fees and costs of HSCT or any procedure. Indirect costs included travelling expenses and earning losses. Social burden of anemia was estimated by anemia related morbidity and mortality. Data were analyzed with SPSSV.17, results showed that AA affected young age group with mean age 30.89±13.39 years, without sex predilection, acquired AA was more common than idiopathic (55.6% vs. 44.4%), however mortality was higher in idiopathic AA (46.2%). Causes of aplasia were exposure to chemicals, drugs and hepatitis in order. Only 63.5% of AA were admitted once and 47.6% in general ward, the mean hospital days for patients with AA was 17.73±11.10, compared to 8.32±6.69 in IDA, P=0.000, also higher socio-economic burden of AA was found compared with IDA. These results denoted that management of AA is still ineffective, and that there is a definite need for a strict plan to prevent incidence of AA, particularly in developing countries where effective management of AA is too expensive and relatively unavailable.

Karyotype and in vitro-response to GM-CSF

The influence of GM-CSF on bone marrow cultures from 13 patients with aplastic anemia, MDS and acute leukemia was studied in a short-term suspension culture system. In each case combined cytogenetic and proliferation analyses were performed with respect to the question, whether chromosome aberrations play a role in the in vitro response to GM-CSF and in order to search for stimulating effects on malignant cells. The responsiveness was compared of aplastic and myelodysplastic cultures on the one hand and of leukemic cells on the other. Our results show that myelodysplastic and aplastic cells display a tendency for reduced susceptibility to GM-CSF as compared to healthy controls, while in leukemic bone marrow the response to the growth factor was significantly enhanced, indicating a leukemia-specific response pattern. In the majority of leukemias analyzed, the presence of cytogenetically abnormal cells in cultures with excessive response to GM-CSF can be taken as a proof for stimulation of malignant cells. The significance of these findings for pathogenesis and prognosis in aplastic anemia, myelodysplasia and leukemia is discussed.

Lymphocyte Subsets in Children with Aplastic Anemia

Twenty-four patients with aplastic anemia (AA) were evaluated with immunologic studies. Patients with posthepatitis AA had decreased proportions of T4 cells, increased proportions of T8 cells, and decreased T4:T8 ratios. Patients with constitutional AA had varied immunologic findings. There were no significant abnormalities in lymphocyte subsets in patients with idiopathic AA. Of the 12 patients who were treated with antithymocyte globulin (ATG), six (50%) responded. Nine of these patients are living 3-27 months after treatment; three of the nine are transfusion dependent. T-cell subsets were not helpful in predicting the response to ATG. Measurements of other immunologic mediators may be more useful with regard to pathophysiology and prognosis in AA.

CFU-gm assay, cytochemical and electron microscopic studies in agar in patients with preleukemic syndrome and aplastic anemia.

Thirty-seven patients with chronic cytopenia were studied using a CFU-gm assay in agar. Cell proliferation was evaluated on days 2, 3, 5, 7, and 10 of incubation. Growth patterns were different in cultures of hematologically healthy persons versus patients with preleukemic syndrome (PL) and aplastic anemia (AA). Three types of PL syndrome and two types of AA (C1 and C2) were distinguished. Bone marrow dysfunction was evaluated further using cytochemistry and electron microscopy to morphologically study cell proliferation in vitro. Cytochemical staining performed in agar demonstrated well-defined maturation defects in myelopoietic precursor cells from the bone marrow of PL patients. Electron microscopic findings of Auer-body-like inclusions in "statu nascendi" in the vacuoles of preleukemic cells supported our results. PL patient groups at high risk for development of overt leukemia and patients with grave prognosis in AA were distinguished. Our results are relevant for the clinical diagnosis and prognosis of patients with cytopenia.

Relationship between Severity and Prognosis in Aplastic Anemia

Relationship between Severity and Prognosis in Aplastic Anemia

Histological prognosis in aplastic anaemia.

In the prognosis of aplastic anaemia, bone marrow biopsy displays several data which were unknown by the myelogram: quantitative evaluation of marrow cellularity; vascular and mesenchymatous lesions; extension of lymphoid or histiocytic infiltration. Nevertheless, the confrontation and value of these signs with the previously used prognosis data issued from clinical and haematological observations is still discussed. The lack of a clear understanding of the bone marrow failure delimitation is perhaps the reason of these differences. We present the histological results of a cooperative protocol concerning 350 cases of bone marrow failure with 220 first bone marrow biopsies examined in triple blind and confronted in a statistical comparison with the mortality in the first 20 months. We evidence the early unfavourable character of oedema and reticulin lesions: and the unconcerned character of cellularity, and lymphocytic and plasmocytic infiltration. These data must be taken into account in an allograft decision.

The prognosis in aplastic anemia

The biphasic shape of the survival curve of 99 patients with aplastic anemia suggested that there may be at least two subgroups of patients with this disease, one with a very short survival and another with a longer survival. Patients who survived for 4 mo or less after the first clinic visit (group A) were different from the patients who survived longer (group B) with respect to their modes of onset, sex, intervals from the onset of symptoms to first clinic visit, and initial hematologic values. These differences suggested that short survival could be predicted from data available at the first contact with the physician. From these measurements, a prognostic index could be calculated which was useful in identifying the patients in group A. Although this method of prognostication needs further testing, if validated, it may prove useful in selecting patients for therapeutic trials and could explain the divergent results in previous studies of androgen treatment of aplastic anemia. When our androgen-treated subjects were compared with subjects with a similar prognostic index who had not received androgens, a beneficial effect of androgen therapy on survival could not be demonstrated.

Effect of Splenectomy on the Response to Platelet Transfusion in Three Patients with Aplastic Anemia

THE variability in the natural history of both acquired and idiopathic aplastic anemia makes it difficult to evaluate the success of any specific program of therapy. With careful attention to supportive care, including transfusion of whole blood and the use of antibiotics, spontaneous remissions do occur. The addition of corticosteroids, splenectomy and, most recently, testosterone to such programs has resulted in many reports of limited success in the treatment of this disease.1 2 3 4 5 However, with the most intensive efforts the prognosis in aplastic anemia remains poor. Even the more favorable studies report mortality rates higher than 50 per cent. In the . . .