Massive apoptosis of bone marrow cells in aplastic anaemia

This article does not have an abstract

Antigenic targets and pathogenicity of anti-aortic endothelial cell antibodies in takayasu arteritis

Anti-endothelial cell antibodies are considered to have an important role in the pathogenesis of Takayasu arteritis (TA). Previously, these antibodies were detected using human umbilical vein endothelial cells, which do not completely represent the antigenicity/functions of aortic endothelial cells, the specific targets in TA. To delineate the precise role of antigenic targets, we investigated such targets as well as the pathogenic mechanism of antibodies directed against aortic endothelial cells (AAECAs) in TA

Clinico-pathological spectrum and novel karyotypic findings in myelodysplastic syndrome: Experience of tertiary care centre in India

Background: Myelodysplastic syndrome (MDS) is a heterogeneous disorder characterized clinically by presence of cytopenia/s. Limited data is available pertaining to the morphological spectrum and cytogenetic profile of Indian MDS patients. The aim of the study was to ascertain the clinco pathological, morphological and cytogenetic spectrum of Indian MDS patients. Material and methods: A retrospective analysis of all patients diagnosed as MDS from June 2012-December 2016 was performed. Their clinical and laboratory data was collated and reviewed.Results: A total of 150 patients of as primary MDS were evaluated with M: F ratio of 1.6:1 and median age of 55.5 years. 64% patients presented with pancytopenia, with thrombocytopenia alone was seen in only 2 cases. There were 66 (44%) cases of MDS-MLD, 33 (22%) MDS-EB 2, 32 (21.3%) MDS–EB 1, 13 (8.6%) cases MDS-SLD and two cases each of MDS-SLD-RS, MDS-MLD-RS and RCC. Cytogenetic data was available in 86/150 patients, 50% of which were abnormal. Complex karyotype was observed to be the commonest abnormality (27.5%). Novel translocations like t(9;22)(q11.2;q34.2) in addition to other abnormalities (n=3), t(2;4)(p25;q23),t(1;5)(p22;q33), t(1;12)(p34;p11.2) and t(5;7;9;)(q13;q32;p22) were observed.Conclusion: The median age of patients in India is almost a decade younger than the western population. Moreover, majority of the patients belonged to the high risk IPSS-R prognostic group (31.4%), followed by intermediate (29%) and very high risk groups (24.4%) in our cohort of patients. Seventy percent individuals, &lt; 40 years belonged to the high prognostic categories, indicating that Indian MDS patients have high disease burden and in turn more likelihood for leukemic transformation.</jats:p

Nocardiosis in patients of chronic idiopathic thrombocytopenic purpura on steroids

We present two cases of chronic idiopathic thrombocytopenic purpura (ITP) on prolonged steroid therapy who developed subcutaneous and brain abscesses due to Nocardia asteroides. The special diagnostic and therapeutic challenges encountered in the patients because of severe thrombocytopenia are being highlighted

Co-existence of AML1-ETO and BCR-ABL1 transcripts in a relapsed patient of acute myeloid leukemia with favorable risk group: A coincidence or clonal evolution?

AbstractPrognosis of acute myeloid leukemia relies heavily on the cytogenetic and molecular abnormalities. AML1-ETO fusion protein resulting from t(8;21), a recurring cytogenetic abnormality, is known to be associated with favorable prognosis. Additional molecular defects may, however, co-operate with the fusion proteins and alter the course of the disease. Among the additional cytogenetic defects, presence of Philadelphia (Ph) chromosome has rarely been documented in this subtype. Little is known about the consequences of its interactions with AML1-ETO, and its effect on morphological and clinical picture. Moreover, Ph+ clones or subclones may appear at any point during the disease course. We herein report one such unusual case of a 26-year-old female, who was diagnosed to have t(8;21) and managed accordingly. During disease relapse after 2.5years, the bone marrow showed extensive eosinophilia and basophilia. Subsequent molecular testing showed the presence of BCR-ABL in addition to the AML1-ETO fusion product

Immune mechanisms in vasculopathies

Soniya Nityanand AB STRACT Most of the inflammatory vasculopathies, termed as vasculitides are considered to be mediated at least in part by immunopathogenic mechanisms. With the recent demonstration of immune cells in atherosclerotic plaques, immune mechanisms are considered to play an important role in atherosclerotic vasculopathies too. The main components involved in the immune-mediated vascular injury are immune complexes, antibodies to vascular wall antigens and T cells. These components may be involved singly or in consort to each other in a particular disease state. The aims of the present study were to investigate the role of (a) T cells in 2 groups of vasculitides - Wegener's granulomatosis (WG) and Takayasu's arteritis (TA); (b) anti-cardiolipin (ACLA) and anti-endothelial cell antibodies (AECA) in TA; (c) ACLA, AECA and circulating immune complexes (CICs) in myocardial infarction and in early onset atherosclerosis of peripheral vasculature; (d) CICs in vasculitis associated with hepatitis B and C infections and the role of anti-viral therapy in such cases. In both WG and TA, there were expanded populations of different AV/BV TCR bearing peripheral blood T cells. In WG a number of these had dramatic magnitudes. The expanded populations were HLA DR+, CD25+, CD28+ and either CD45RA+ or RO+. In WG, a more detailed study of the expanded populations showed them to persist in an activated state and in same magnitude for the total observation time of 28-38 months, irrespective of the disease going into clinical remission. Functionally the expanded populations were activated. These populations expressed and secreted the studied cytokines IL-2, IL-4, IFNy and GM-CSF. The activated status and secretion of cytokines by the expanded populations shows their involvement in the pathogenesis of WG. Most of the expanded populations were clonal and a further study would help in the elucidation of the inciting antigen. A higher prevalence of ACLA and AECA was observed in TA patients with a correlation with disease activity. A higher prevalence of ACLA and AECA was also observed in MI and peripheral atherosclerosis patients. A significant observation was that the levels of IgG and IgA ACLA at 50 years of age were predictive of the susequent occurrence of MI between 50-70 years of age and mortality related to it, independent of other conventional risk factors. Fifty % of peripheral atherosclerosis patients had CICs with a proppensity for those with C4 null alleles to have CICs. All the 7 patients with vasculitis associated with hepatitis B and C infections had high levels of CICs/cryoglobulins containing hepatitis Ags/Abs/genome. With anti-viral therapy all the 7 patients showed a rapid clinical improvement in the vasculitis and a concomitant sharp decline in CICs/cryoglobulins. 6 patients went into long lasting remissions with clearence of hepatitis Ags/genome from serum and CICs

Serum Albumin Predicts Survival in Indian Adult Diffuse Large B cell Lymphoma Patients in the Rituximab Era

Abstract Objective: The present study was done to evaluate the prognostic impact of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and serum albumin levels in the treatment outcome of Indian diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Patients and Methods: We retrospectively analyzed the data (2013–2016) of 135 newly diagnosed DLBCL cases ≥18 years of age. All patients received Rituximab-Cyclophosphamide, Adriamycin, Vincristine, Prednisone (R-CHOP) chemotherapy. The analysis was carried out to assess the overall survival (OS) and progression-free survival (PFS) and the prognostic factors predicting the outcome. Results: Of the 135 patients in the study, 89 (65.9%) had B-symptoms, 20 (14.8%) had bulky disease, 79 (58.5%) had advanced disease (Stage III and IV), and 29 (21.5%) had primary extranodal involvement. Serum albumin ≤3.5 g% was present in 71 (52.6%) patients. About 74 (54.8%) cases were risk stratified to NCCN-IPI high-intermediate-risk group, while 18 (13.3%) patients were categorized into high-risk group. The median PFS and OS of our study cohort were 19 months (95% confidence interval [CI] = 2.59–35.4) and 38 months (95% CI = 9.02–55.68), respectively. Serum albumin ≤3.5 g/dl was significantly associated with poor OS (hazard ratio [HR] = 3.99, 95% CI = 2.25–7.07, P &lt; 0.001) and PFS (HR = 3.71, 95% CI = 2.20–6.26, P &lt; 0.002). Similarly, low NCCN-IPI (&lt;4) was significantly associated with improved OS (HR = 0.21, 95% CI = 0.09–0.47, P &lt; 0.005) and PFS (HR = 0.19, 95% CI = 0.09–0.41, P &lt; 0.001), respectively. These two factors (serum albumin and NCCN-IPI) retained their prognostic significance with respect to OS and PFS in the multivariate analysis. Conclusion: The NCCN-IPI prognostic model and serum albumin levels have independent prognostic significance in Indian DLBCL patients. Serum albumin is a readily available, easy to standardize, and cheap investigation requiring no specialized expertise and holds promise for being incorporated in future DLBCL prognostic risk models.</jats:p

Expression of interferon-γ and tumor necrosis factor-α in bone marrow T cells and their levels in bone marrow plasma in patients with aplastic anemia

Immune-mediated stem cell damage has been postulated to be responsible for disease initiation and progression in aplastic anemia (AA). It is hypothesized that T lymphocytes play a major role in destroying the bone marrow (BM) stem cells of AA patients by infiltrating the BM and secreting excessive levels of anti-hematopoietic cytokines, interferon-gamma (IFN- &#947;), and tumor necrosis factor-alpha (TNF-&#945;). We undertook this study to assess the pathogenic significance of anti-hematopoietic cytokines such as IFN- &#947; and TNF-&#945; in BM T cells and plasma of AA patients. Significantly elevated levels of IFN- &#947; and TNF-&#945; were found in the BM plasma of AA patients compared to controls (p=0.05 and 0.006, respectively). Intracellular IFN- &#947; and not TNF-&#945; in BM CD3+ T cells of AA patients was significantly higher compared to controls (p=0.04 and p=0.2, respectively). A follow-up analysis of expression of these cytokines in BM T cells and their levels in BM plasma in five AA patients before and 180 days (6 months) after antithymocyte globulin (ATG) and cyclosporin A (CsA) therapy showed a decline 180 days after therapy compared to pre-therapy. We thus conclude that increased production of both IFN-&#947; and TNF-&#945; in the BM may contribute to disease pathogenesis in AA and ATG therapy may induce hematological remission by suppressing the elevated levels of IFN-&#947; and TNF- &#945; in AA BM

Serum albumin predicts survival in Indian adult diffuse large B cell lymphoma patients in the rituximab era

Objective: The present study was done to evaluate the prognostic impact of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and serum albumin levels in the treatment outcome of Indian diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Patients and Methods: We retrospectively analyzed the data (2013–2016) of 135 newly diagnosed DLBCL cases ≥18 years of age. All patients received Rituximab-Cyclophosphamide, Adriamycin, Vincristine, Prednisone (R-CHOP) chemotherapy. The analysis was carried out to assess the overall survival (OS) and progression-free survival (PFS) and the prognostic factors predicting the outcome. Results: Of the 135 patients in the study, 89 (65.9%) had B-symptoms, 20 (14.8%) had bulky disease, 79 (58.5%) had advanced disease (Stage III and IV), and 29 (21.5%) had primary extranodal involvement. Serum albumin ≤3.5 g% was present in 71 (52.6%) patients. About 74 (54.8%) cases were risk stratified to NCCN-IPI high-intermediate-risk group, while 18 (13.3%) patients were categorized into high-risk group. The median PFS and OS of our study cohort were 19 months (95% confidence interval [CI] = 2.59–35.4) and 38 months (95% CI = 9.02–55.68), respectively. Serum albumin ≤3.5 g/dl was significantly associated with poor OS (hazard ratio [HR] = 3.99, 95% CI = 2.25–7.07, P < 0.001) and PFS (HR = 3.71, 95% CI = 2.20–6.26, P < 0.002). Similarly, low NCCN-IPI (<4) was significantly associated with improved OS (HR = 0.21, 95% CI = 0.09–0.47, P < 0.005) and PFS (HR = 0.19, 95% CI = 0.09–0.41, P < 0.001), respectively. These two factors (serum albumin and NCCN-IPI) retained their prognostic significance with respect to OS and PFS in the multivariate analysis. Conclusion: The NCCN-IPI prognostic model and serum albumin levels have independent prognostic significance in Indian DLBCL patients. Serum albumin is a readily available, easy to standardize, and cheap investigation requiring no specialized expertise and holds promise for being incorporated in future DLBCL prognostic risk models