Survival of non-Hodgkin lymphoma patients with and without HIV infection in the era of combined antiretroviral therapy
ABSTRACT To investigate the survival outcomes for non-Hodgkin lymphoma (NHL) in HIV-infected vs. uninfected patients from the same integrated healthcare system, and to identify prognostic factors for HIV-related NHL in the era of combined antiretroviral therapy.
A cohort study.
Incident NHL diagnosed between 1996 and 2005 were identified from members of Kaiser Permanente California Health Plans. Two-year all-cause and lymphoma-specific mortality by HIV status were examined using multivariable Poisson regression. Among HIV-infected patients, prognostic factors of demographics, lymphoma, and HIV-related characteristics for the same outcomes were also examined.
A total of 259 HIV-infected and 8230 HIV-uninfected incident NHL patients were evaluated. Fifty-nine percent of HIV-infected patients died within 2 years after NHL diagnosis as compared with 30% of HIV-uninfected patients. HIV status was independently associated with a doubling of 2-year all-cause mortality (relative risk = 2.0, 95% confidence interval 1.7-2.3). This elevated mortality risk for HIV-infected patients was similar for all race groups, lymphoma stages, and histologic subtypes. HIV-infected patients with CD4 cell count below 200 cells/microl, prior AIDS-defining illness, or both were also at increased risk for lymphoma-specific mortality as compared with HIV-uninfected patients. Among HIV-infected NHL patients, significant prognostic factors for overall mortality included prior AIDS-defining illness and Burkitt's subtype.
HIV-infected patients with NHL in the combined antiretroviral therapy era continue to endure substantially higher mortality compared with HIV-uninfected patients with NHL. Better management and therapeutic approaches to extend survival time for HIV-related NHL are needed.
SourceAvailable from: scielo.clRevista medica de Chile 02/2012; 140(2):243-250. DOI:10.4067/S0034-98872012000200015 · 0.37 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Little is known about survival and factors associated with mortality after cancer diagnosis among persons infected with human immunodeficiency virus (HIV). Using Poisson regression, we analyzed incidence rates of acquired immune deficiency syndrome (AIDS)-defining cancers (ADC), non-AIDS-defining infection-related cancers (NADCI), and non-AIDS-defining noninfection-related cancers (NADCNI) among HIV Outpatient Study participants seen at least twice from 1996-2010. All-cause mortality within each cancer category and by calendar period (1996-2000, 2001-2005, 2006-2010) were examined using Kaplan-Meier survival methods and log-rank tests. We identified risk factors for all-cause mortality using multivariable Cox proportional hazard models. Among 8350 patients, 627 were diagnosed with 664 cancers. Over the 3 time periods, the age- and sex-adjusted incidence rates for ADC and NADCNI declined (both P < .001) and for NADCI did not change (P = .13). Five-year survival differed by cancer category (ADC, 54.5%; NADCI, 65.8%; NADCNI, 65.9%; P = .018), as did median CD4 cell count (107, 241, and 420 cells/mm(3); P < .001) and median log10 viral load (4.1, 2.3, and 2.0 copies/mL; P < .001) at cancer diagnosis, respectively. Factors independently associated with increased mortality for ADC were lower nadir CD4 cell count (hazard ratio [HR] = 3.02; 95% confidence interval [CI], 1.39-6.59) and detectable viral load (≥400 copies/mL; HR = 1.72 [95% CI, 1.01-2.94]) and for NADCNI, age (HR = 1.50 [95% CI, 1.16-1.94]), non-Hispanic black race (HR = 1.92 [95% CI, 1.15-3.24]), lower nadir CD4 cell count (HR = 1.77 [95% CI, 1.07-2.94]), detectable viral load (HR = 1.96 [95% CI, 1.18-3.24]), and current or prior tobacco use (HR = 3.18 [95% CI, 1.77-5.74]). Since 1996, ADC and NADCNI incidence rates have declined. Survival after cancer diagnosis has increased with concomitant increases in CD4 cell count in recent years. Advances in HIV therapy, including early initiation of combination antiretroviral therapy, may help reduce mortality risk among HIV-infected persons with cancer.03/2014; 1(1):ofu012. DOI:10.1093/ofid/ofu012
[Show abstract] [Hide abstract]
ABSTRACT: Purpose: HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente California between 1996 and 2007. Design: Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender and race. Twenty-three markers in the following categories were examined using immunohistochemistry: (1) cell cycle regulators, (2) B-cell activators, (3) anti-apoptotic proteins, and (4) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher's exact test. For markers differentially expressed in HIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for international prognostic index, cell-of-origin phenotype and DLBCL morphologic variants. Results: Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-beta2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) were significantly elevated in HIV-related DLBCLs, while expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased two-year mortality in HIV-infected patients [relative risk =3.092.80 (0.90-10.550.90-8.70)] in multivariable logistic regression. Conclusion: These results suggest that HIV-related DLBCL pathogenesis more frequently involve cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients. Copyright © 2015, American Association for Cancer Research.Clinical Cancer Research 01/2015; 21(6). DOI:10.1158/1078-0432.CCR-14-2083 · 8.19 Impact Factor