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ABSTRACT: HIV-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder caused by infection with human herpesvirus-8. The disease follows a relapsing and remitting clinical course, with marked systemic symptoms during an active attack, which can prove fatal. Its incidence is rising, and new data indicate the utility of the anti-CD20 monoclonal antibody rituximab at inducing remissions in both first- and second-line settings, although biomarkers associated with relapse have not been previously identified. In 52 individuals with a histologic diagnosis of HIV-MCD, we performed univariate and multivariate analyses to predict factors associated with an HIV-MCD attack. Although a younger age (< 50 years) was associated with an attack, the strongest association was observed with plasma levels of human herpesvirus-8 DNA. Rising levels predicted an attack (hazard ratio = 2.9; 95% confidence interval, 1.3-6.7), and maintenance therapy with rituximab should be considered in these individuals.
Blood 04/2011; 118(2):271-5. · 9.90 Impact Factor
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Jonathan Shamash,
Justin Stebbing,
Chris Sweeney,
Guru Sonpavde,
Steve Harland,
Guy Dawkins,
Cathryn Brock,
Walter Abelman,
Peter Wilson, Adam Sanitt,
Tim Oliver,
Thomas Powles
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ABSTRACT: The objective of this study was to identify subgroups of patients with castrate-resistant prostate cancer (CRPC) who had a prolonged response to combined dexamethasone and diethylstilbestrol (DS) therapy by constructing a prognostic index.
Multivariate and cutoff point analyses with bootstrapping were performed 1 month after commencing DS therapy, and data were validated using an independent external dataset.
The median overall survival for 145 patients was 18.3 months (95% confidence interval [CI], 15.4-23.3 months). Only 2 factors were significant on multivariate analysis: a prostate-specific antigen (PSA) level below the median at the start of DS therapy and a decline>50% in the PSA level after 1 month on DS therapy. Subsequent cutoff point analyses revealed that a PSA level<88 ng/mL at the start of DS therapy and a reduction>53.1% in PSA after the first month of treatment were the most significant factors. These 2 factors were used to construct a prognostic index, which was validated successfully by the external dataset (median overall survival, 18.3 months [95% CI, 16.4-28.0 months]; concordance, 72% [95% CI, 68%-76%]). The prognostic index identified 3 prognostic groups: The 2-year overall survival rate for these 3 groups was 68% (95% CI, 57%-98%) for the good prognostic group, 40% (95% CI, 31%-52%) for the intermediate prognostic group, and 12% (95% CI, 5%-25%) for the poor prognostic group.
The easy-to-use prognostic index that the authors developed was able to identify a subgroup of patients with CRPC who had prolonged survival only 1 month after starting DS therapy.
Cancer 08/2010; 116(15):3595-602. · 4.77 Impact Factor
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ABSTRACT: A prognostic index for AIDS-associated Kaposi's sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy (HAART) was based on routine clinical and laboratory characteristics. Because immune subset measurement is often performed in HIV-positive individuals, we examined whether these were predictive of mortality independently of the prognostic index, or could predict time to progression of KS.
We performed univariate and multivariate Cox regression analyses on a data set of 326 individuals with AIDS-associated KS to identify immune subset covariates predictive of overall survival and time to progression. Adaptive (CD8 T cell and CD19 B cell) and innate (CD16/56 natural-killer cell) immune parameters were studied by flow cytometry.
In univariate analyses, all three immune subsets had significant effects on overall survival (P < .025). In multivariate analyses including the prognostic index, only CD8 counts remained significant (P = .026), although its effect on the overall prognostic index is small. An increase of 100 cells/mm3 in the CD8 count confers a 5% improvement in overall survival. Individuals with a higher CD8 count did not have an increased time to progression. Patients who were already on HAART at the time of KS diagnosis did not have a shorter time to progression than those who were antiretroviral naïve at KS diagnosis.
The CD8 count appears to provide independent prognostic information in individuals with AIDS-associated KS. Measurement of the CD8 count is clinically useful in patients with KS.
Journal of Clinical Oncology 07/2007; 25(16):2230-5. · 18.37 Impact Factor
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ABSTRACT: AIDS-associated Kaposi's sarcoma remains common in individuals with HIV-1 infection in the era of highly active antiretroviral therapy (HAART). We developed a simple model for predicting mortality on the basis of clinical characteristics present at the time of diagnosis of Kaposi's sarcoma.
Of 5873 individuals with HIV-1 infection, 326 (6%) developed Kaposi's sarcoma; for 262 (80%) this was their first AIDS-defining illness. We did univariate and multivariate Cox regression analyses to identify covariates predictive of overall survival and validated our model with an independent data set of 446 patients with Kaposi's sarcoma.
In the primary model, we developed a prognostic score from 0 to 15 starting at 10. Having Kaposi's sarcoma as the AIDS-defining illness (-3 points) and increasing CD4 count (-1 point for every complete 100 cells per mm3) improved prognosis; age of 50 years or older (2 points) and having another AIDS-associated illness at the same time (3 points) conveyed a poorer prognosis. In individuals with prognostic scores of 0, 5, 10, and 15, probability of survival at 1-year was 0.993, 0.967, 0.834, and 0.378, and at 5 years was 0.984, 0.918, 0.631, and 0.084, respectively. Increasing prognostic score by 1 increased 1-year death hazard ratio by 40% (95% CI 28-53%; bootstrapped hazard ratio 1.39, 1.25-1.51). The index had concordance of 76.8% (71.7-82.3).
We identified four prognostic factors that can be used to obtain an accurate prognostic index at diagnosis of AIDS-associated Kaposi's sarcoma. This index is widely applicable and can be used to guide therapeutic options.
The Lancet 06/2006; 367(9521):1495-502. · 38.28 Impact Factor
