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Disease Biology (disease + biology)
Selected AbstractsDisease biology rather than age is the most important determinant of survival of patients , 60 years with acute myeloid leukemia treated with uniform intensive therapyCANCER, Issue 10 2005Vikas Gupta M.D. Abstract BACKGROUND The objectives of the current study were to evaluate the outcome of patients , 60 years with acute myeloid leukemia (AML) treated uniformly with high-dose daunorubicin containing induction and modified high-dose cytosine arabinoside containing postremission therapy, and to identify factors predictive of complete disease remission (CR) and survival. METHODS Between 1998 and 2002, the authors treated 117 newly diagnosed patients (acute promyelocytic leukemia excluded) with AML , 60 years (median, 67 years; range, 60,82 years). Karyotype (Medical Research Council classification) at diagnosis was categorized as good risk (n = 3), intermediate risk (n = 69), adverse risk (n = 26), and suboptimal/not done (n = 19). A normal karyotype was seen in 41 patients and 40 (34%) had secondary AML. RESULTS The outcome of induction included the following: CR, 62 (53%); early death, 5 (4%); death during hypoplasia, 14 (12%); and resistant disease, 36 (31%). The 3-year event-free (EFS) and overall survival (OS) rates were 9% (95% confidence interval [95% CI], 3,16%) and 17% (95% CI, 9,29%), respectively. In a univariate analysis, cytogenetics, lactate dehydrogenase level, leukocyte count, and performance status were the significant factors for EFS and OS. Age was not a significant prognostic factor for either CR or survival. In a multivariate model, adverse-risk cytogenetics, previous history of myelodysplastic syndrome or antecedent hematologic disorder, and high leukocyte count (> 30 × 109/L) were independent adverse prognostic factors for survival. The impact of adverse karyotype on EFS and OS was time dependent and was observed after 50 and 150 days, respectively. CONCLUSIONS The authors concluded that candidacy for intensive therapy in older patients should be based on biologic features of disease and fitness, rather than on age. Cancer 2005. © 2005 American Cancer Society. [source] Children and adults with acute lymphoblastic leukaemia have similar gene expression profilesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005E. Kuchinskaya Abstract:,Objectives:,To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis. Methods:,The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix. Results:,Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype. Conclusions:,In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity. [source] Genetic and phenotypic analysis of B-cell post-transplant lymphoproliferative disorders provides insights into disease biologyHEMATOLOGICAL ONCOLOGY, Issue 4 2008Efsevia Vakiani Abstract B-cell post-transplant lymphoproliferative disorders (PTLD) are classified as early lesions, polymorphic lymphomas (P-PTLD) and monomorphic lymphomas (M-PTLD). These morphologic categories are thought to reflect a biologic continuum, although supporting genetic data are lacking. To gain better insights into PTLD pathogenesis, we characterized the phenotypes, immunoglobulin (Ig) gene alterations and non-Ig gene (BCL6, RhoH/TTF, c-MYC, PAX5, CIITA, BCL7A, PIM1) mutations of 21 PTLD, including an IM-like lesion, 8 P-PTLD and 12 M-PTLD. Gene expression profile analysis was also performed in 12 cases. All PTLD with clonal Ig rearrangements showed evidence of germinal centre (GC) transit based on the analysis of Ig and BCL6 gene mutations, and 74% had a non-GC phenotype (BCL6,±,MUM1+). Although surface Ig abnormalities were seen in 6/19 (32%) PTLD, only three showed ,crippling' Ig mutations indicating other etiologies for loss of the B-cell receptor. Aberrant somatic hypermutation (ASHM) was almost exclusively observed in M-PTLD (8/12 vs. 1/8 P-PTLD) and all three recurrent cases analysed showed additional mutations in genes targeted by ASHM. Gene expression analysis showed distinct clustering of PTLD compared to B-cell non-Hodgkin lymphomas (B-NHL) without segregation of P-PTLD from non-GC M-PTLD or EBV+ from EBV, PTLD. The gene expression pattern of PTLD appeared more related to that of memory and activated B-cells. Together, our results suggest that PTLD represent a distinct type of B-NHL deriving from an antigen experienced B-cell, whose evolution is associated with accrual of genetic lesions. Copyright © 2008 John Wiley & Sons, Ltd. [source] The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma,HEMATOLOGICAL ONCOLOGY, Issue 4 2004E. Hatjiharissi Abstract The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-,), which have angiogenic potential and interleukin-6 (IL-6), IL-1,, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-,) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-,, TGF-,, IL-1, did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology. Copyright © 2005 John Wiley & Sons, Ltd. [source] Socioeconomic Status and Survival in Older Patients with MelanomaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2006Carlos A. Reyes-Ortiz MD OBJECTIVES: To determine the association between socioeconomic status (SES) and survival in older patients with melanoma. DESIGN: Retrospective cohort study. SETTING: Surveillance, Epidemiology and End Results (SEER): a population-based cancer registry covering 14% of the U.S. population. PARTICIPANTS: Twenty-three thousand sixty-eight patients aged 65 and older with melanoma between 1988 and 1999. MEASUREMENTS: Outcome was melanoma-specific survival. Main independent variable was SES (measured as census tract median household income) taken from the SEER-Medicare linked data. RESULTS: Subjects residing in lower-income areas (,$30,000/y) had lower 5-year survival rates (88.5% vs 91.1%, P<.001) than subjects residing in higher-income areas (>$30,000/y). In Cox proportional hazard models, higher income was associated with lower risk of death from melanoma (hazard ratio=0.88, 95% confidence interval=0.79,0.98, P=.02) after adjusting for sociodemographics, stage at diagnosis, thickness, histology, anatomic site, and comorbidity index. There was an interaction effect between SES and ethnicity and survival from melanoma. For whites and nonwhites (all other ethnic groups), 5-year survival rates increased as income increased, although the effect was greater for nonwhites (77.6% to 90.1%, 1st to 5th quintiles, P=.01) than for whites (89.0% to 91.9%, 1st to 5th quintiles, P<.001). CONCLUSION: Older subjects covered by Medicare residing in lower-SES areas had poorer melanoma survival than those residing in higher-SES areas. Further research is needed to determine whether low SES is associated with late-stage disease biology and poorer early detection of melanoma. [source] Serum immunoglobulin free light chain measurements and heavy chain isotype usage provide insight into disease biology in patients with POEMS syndrome,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010Trista Stankowski-Drengler POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare paraneoplastic syndrome in which nearly all patients have a monoclonal lambda restricted plasma cell disorder. We investigated whether patients with POEMS have abnormal serum immunoglobulin free light chain (FLC) ratios. Fifty patients with newly diagnosed POEMS syndrome were assessed. Cystatin C levels were measured to discern whether subclinical renal insufficiency could account for FLC elevations in the presence of a normal FLC ratio. Forty-five patients (90%) had elevated lambda FLC; however, only nine (18%) had abnormal FLC ratios. The rise in serum FLC of POEMS patients appeared to be multifactorial,both a function of subclinical renal insufficiency and polyclonal activation of medullary and extramedullary plasma cells. Those patients expressing a clonal IgA were more likely to have clonal plasmacytosis observed on iliac crest biopsy than those with IgG. In summary, serum immunoglobulin profiles are unique in POEMS syndrome as compared with other plasma cell disorders. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis,prognostic relevance is independent of IPSS or karyotype,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Ayalew Tefferi The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients (,24%) required transfusions at diagnosis whereas 22 (,9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotype-independent prognostic weight of transfusion status. Among IPSS intermediate-1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Prognostic factors in adult acute lymphoblastic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2010Jacob M. Rowe Summary Treatment of acute lymphoblastic leukaemia (ALL) in adults presents a formidable challenge. While overall results have improved over the past 3 decades, the long-term survival for patients aged less than 60 years is only in the range of 30,40% and is 10,15% if between 60 and 70 years and <5% for those over 70 years. The historic lack of clear-cut biological prognostic factors has led to over- or under-treatment of some patients. Response to initial therapy is an important prognosticator of outcome based on disease biology, as well as pharmacogenetics, which include the patient's response to drugs given. The more widespread availability of allogeneic transplantation and reduced-intensity regimens for older patients have opened up this curative modality to a greater number of patients. Hopefully, those options, as well as novel cytogenetic and molecular markers, will enable a better selection of patients who undergo intensive therapies and finally break the 30,40% cure barrier for adults with ALL. [source] | ||||||||||