Non-Hodgkin Lymphoma In HIV-infected Patients Research Articles

Annals for Educators - 3 January 2017

Annals for Educators - 3 January 2017

Is Viral Hepatitis Associated with Non-Hodgkin Lymphoma in HIV-infected Patients?

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have been associated with an increased risk for non-Hodgkin lymphoma (NHL) in

Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study.

Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Cohort study. 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. A total of 52479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. European Union Seventh Framework Programme.

RISK FACTORS FOR THE DEVELOPMENT OF NON-HODGKIN’S LYMPHOMA IN PATIENTS WITH HIV AND HEPATITIS С COINFECTION

The objective of the study was to investigate risk factors for the development of non-Hodgkin's lymphoma (NHL) in HIV-infected patients with hepatitis С virus (HCV) coinfection. A total of 37 HIV-positive subjects with NHL treated in the Moscow Center for Prevention and Control of AIDS between 2009 and 2013 were included in the study. HIV patients were divided into 2 groups: 23 cases with HCV coinfection and 14 patients without HCV coinfection. At the time of making the diagnosis of NHL 90% of patients had CD4 cell count < 350 cell/mm 3. The mean CD4 cell count in the first group (120±123 cell/mm 3) was significantly lower (p=0,035), than in patients without HCV coinfection (267±253 cell/mm3). At the time of making the diagnosis of NHL 70% of patients had HIV viral load ≥5,00 log10. The mean viral load was 5,47±1,09 log10 copies/ml in the first group and 4,06±2,03 log10 copies/ml in the second group (p=0,033). At the time of making the diagnosis of NHL 78% of patients did not receive combination antiretroviral therapy (cART). In most patients who received cART virologic suppression unsufficient and CD4 cell count remained to be low. Risk factors associated with an increased risk of NHL in HIV-infected patients with HCV coinfection are low CD4 cell count, high HIV viral load and lack of effective cART. Timely initiation of cART followed by complete virologic suppression and CD4 recovery are key factors to prevent NHL in HIV-infected patients.

Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults

Given the well documented occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients who recently started combination antiretroviral therapy (cART), we examined whether cART initiation increased the risk of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) using data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration. A nested matched case-control study design was used to assess the effects of individual CD4 cell trajectories and exposure to cART close to the time of cancer diagnosis. Cases were patients diagnosed with either cancer during follow-up with a minimum of two consecutive CD4 cell readings within the year preceding diagnosis. For each case, up to 10 controls, matched by sex and cohort, were selected by random sampling. Changes in CD4 cell count, calculated by simple and piecewise linear regression, and recent exposure to cART were compared within matched case-control sets using conditional logistic regression. Using data on 689 cases and 4588 controls, we found that an initially low and decreasing CD4 cell count during the year prior to cancer diagnosis is predictive of both Kaposi sarcoma and NHL. Most of this cancer risk is explained by the immunodeficiency characteristic of the period before cART initiation; however, an increased cancer risk was seen in patients who initiated cART in the previous 3 months (odds ratio 2.31; 95% confidence interval 1.33, 4.00). Although IRIS may transiently increase the risk of Kaposi sarcoma or NHL in HIV-infected patients, the timely initiation of cART remains the best strategy to avoid the development of these malignancies.

Non-Hodgkin's Lymphoma in Patients With Human Immunodeficiency Virus Infection in Taiwan

Non-Hodgkin's lymphoma (NHL) is the second most common acquired immunodeficiency syndrome-defining malignancy with a high mortality rate. This study aimed to describe changes in the incidence and clinical characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in a referral hospital for HIV care. The medical records of HIV-infected patients diagnosed with NHL between June 1994 and December 2006 were retrospectively reviewed. Risk stratification of each patient was evaluated using the International Prognostic Index (IPI). Case patients were followed at least for 2 years to assess the 2-year survival rates. During the 12-year period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of differentiation 4 count was 82 cells/microL (range, 2-477 cells/microL) at diagnosis. Before the introduction of highly active antiretroviral therapy (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year survival rate did not differ significantly between patients diagnosed in the pre-HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients receiving HAART for more than 6 months had better survival rates (p < 0.05). A low IPI score was a good prognostic factor predictive of a patient's outcome. The incidence of NHL in HIV-infected patients declined significantly in the HAART era. Despite the introduction of HAART, the short-term survival of the patients with NHL remained poor. The IPI was a good predictor for survival.

Interleukine-2 Therapy Does Not Increase the Risk of Hodgkin or Non-Hodgkin Lymphoma in HIV-Infected Patients: Results From FHDH ANRS CO4

Concerns have been raised about a possible excess risk of lymphomas in HIV-infected patients exposed to interleukin 2 (IL-2) therapy. Here we compared the risks of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) in IL-2-treated and IL-2-untreated HIV-infected patients. Patients monitored through the French Hospital Database on HIV between May 1, 1995, and December 31, 2005, were enrolled in this study. Lymphomas that occurred between the day after study entry and the end of follow-up were eligible for analysis. Poisson regression models were used in 2 separate analyses to quantify the possible relationship between IL-2 therapy and the incidence of NHL and HL. The IL-2-treated group consisted of 861 patients and the IL-2-untreated group of 77,605 patients. Follow-up lasted a total of 3643 and 382,720 person-years, respectively. After adjustment for sex and time-updated age, period, the CD4 cell counts, the plasma HIV RNA levels, and AIDS status, the relative rates of NHL and HL associated with IL-2 therapy were 0.64 (95% confidence interval, 0.25 to 1.65) and 0.33 (95% confidence interval, 0.04 to 2.86), respectively. In this large observational study, IL-2 therapy did not increase the risk of lymphoma, either NHL or HL, in HIV-infected patients.

Impact of Combined Anti-Retroviral Therapy on HIV-Associated Non-Hodgkin-Lymphoma - a Prospective European Multi-Cohort Study on Behalf of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group

Background: Following its introduction in 1996, combination antiretroviral therapy (cART) has led to a substantial reduction in HIV-associated morbidity and mortality. The decline has, however, been less pronounced for non-Hodgkin lymphoma (NHL) than for other HIV-related complications, and NHL has become the most common cancer associated with HIV. Within the framework of a large prospective European multi-cohort project, the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), we studied the incidence and risk factors for the development and survival of NHL in HIV-infected patients in the cART era.Methods: We analyzed the data of HIV- infected adult patients (aged >16 years) who were cART naïve at inclusion and started cART after 01.01.1998, at a time when cART had become well established and widely used in Europe. cART was defined as a regimen of at least 3 antiretroviral drugs. Patients had to have CD4 count measurements available before the start of cART and the diagnosis of NHL. Patients developing NHL before receiving cART (“not on cART”) and patients developing NHL while receiving cART (“on cART”) were analyzed separately. Both patients with Primary Brain Lymphoma (PBL) and systemic NHL were included in the analysis. Incidence rates were calculated based on the Poisson distribution; risk factors were estimated using crude and adjusted Weibull models, with random effects to account for heterogeneity between cohorts. Models with time varying covariates were used to explore the effects of CD4 cell counts and plasma HIV-RNA loads over time. Survival was estimated using Kaplan-Meier life table probabilities, with 95% confidence intervals (95% CI).Results: For the incidence analysis 56,305 patients from 22 cohort studies across Europe with 212,042 person-years at risk were evaluated. The incidence for NHL (both systemic NHL and PBL) in patients not on cART was 519 (95% CI 448 to 602) per 100,000 personyears compared to 229 (95% CI 208 to 252) per 100,000 person-years in those on cART. The corresponding rates for PBL were 57 (95% CI 36 to 89) per 100,000 person-years and 24 (95% CI 18 to 33) per 100,000 person years. In cART naïve patients risk factors for NHL were older age and low CD4 cell count nadirs. When included as time up-dated variables, high plasma HIV-1 RNA loads and low CD4 cell counts emerged as important risk factors. In patients receiving cART risk factors included low CD4 cell count nadirs, older age, and groups associated with HHV-8 infection, i.e. men having sex with men and patients with a previous diagnosis of Kaposi Sarcoma. Time up-dated HIV-1 RNA plasma concentration and CD4 cell count were also associated with developing NHL while on cART. For the survival analysis 847 NHL patients were eligible. Of those, 364 (43%) were cART naïve at diagnosis of NHL. After one year 66% (95% CI 63%–70%) of patients with systemic NHL and 54% (95% CI 43%–65%) of patients with PBL were alive. Risk factors for death were diagnosis of PBL, low CD4 cell count nadir and history of injection drug use.Conclusions: Combined anti-retroviral therapy reduces the risk of developing NHL. In the era of cART more advanced immunodeficiency is the dominant risk factors for developing NHL both in patients receiving and not receiving cART. Two thirds of patients diagnosed with HIV-related NHL other than PBL survive for longer than one year after diagnosis. Survival is poorer in patients diagnosed with PBL.

High Proportion of T-Cell Systemic Non-Hodgkin Lymphoma in HIV-Infected Patients in Lima, Peru

Few reports have described the clinical and pathologic characteristics of HIV-related systemic non-Hodgkin lymphoma (sNHL) in developing countries. We aimed to determine these characteristics from a national HIV reference center in Peru and to evaluate factors associated with survival. A retrospective/prospective study of patients with HIV-related sNHL from the Guillermo Almenara General Hospital in Lima, Peru between 1993 and 2004. Clinical characteristics at diagnosis included age, gender, risk behavior, previous AIDS diagnosis, opportunistic diseases, previous highly active antiretroviral therapy, Karnofsky score, origin, clinical stage and B-cell symptoms of sNHL, and CD4 cell count. Cases of sNHL were classified according to the criteria of the World Health Organization. Thirty-three cases were identified (26 male, age range: 38 +/- 10 years). Ten patients (30%) had a prior history of AIDS, 14 (42%) had a Karnofsky score of <or=70, and 18 (56%) had clinical stage IV sNHL. The CD4 cell count median value was 111 cells/microL (n = 25). Twenty-four cases (73%) were B-cell sNHL, and 9 cases (27%) were T-cell sNHL, both from peripheral cells. Nineteen cases of sNHL were extranodal: 15 of B-cell origin and 4 of T-cell origin. Eighteen cases of B-cell sNHL had diffuse large cell histologic findings, and all cases of T-cell sNHL were unspecified. Although there were no significant differences in clinical characteristics between phenotypes, patients with T-cell sNHL had less aggressive disease and a better survival rate. A high proportion of T-cell sNHL cases was found at an HIV reference center in Peru. Clinical characteristics were similar between B-cell and T-cell lymphoma patients. T-cell lymphoma was less aggressive, and patients with T-cell lymphoma had a better survival rate than those with B-cell lymphoma.

Systemic non-Hodgkin lymphoma in HIV-infected patients with effective suppression of HIV replication: persistent occurrence but improved survival.

The incidence of systemic non-Hodgkin lymphoma (NHL) has only slightly decreased since the introduction of highly active antiretroviral therapy (HAART), suggesting that current antiretroviral strategies do not eliminate the lymphoma risk. This study evaluates the evolving characteristics of HIV and NHL between the pre-HAART and the post-HAART periods in 246 HIV-infected NHL patients from a single institution. Major HIV-related characteristics were similar in the two periods. Most patients in the post-HAART period presented with unknown (23%), untreated (16%), or uncontrolled (37%) HIV infection. Despite an increased frequency of advanced stage IV disease in the post-HAART period (68% vs. 53%, p =.03), the overall survival has improved, with a 2-year survival probability of 61.6% versus 35.9%, (p <.001). This was associated with an increased complete remission rate (69% vs. 55%, p =.04) and the generalization of more intensive chemotherapy regimens. Most patients (76%) who developed NHL in the post-HAART period had uncontrolled HIV replication. However, 27 patients (24%) developed NHL despite an effective viral suppression at NHL diagnosis. Patients who were naive to any antiretroviral therapy at NHL diagnosis had an overall survival probability very similar to that of patients with controlled HIV replication. Improvement in the overall survival rate in the post-HAART period was associated with more intensive chemotherapy regimens, increased complete remission rate, and a likely benefit of continuation or introduction of HAART.

Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy

AbstractThis study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (≥3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox proportional hazard models. Over 26 764 person-years of prospective follow-up (PYF) from May 1994 to December 2000, the incidence of NHL decreased from 1.99 (95% confidence interval, 1.51-2.47) before September 1995 to 0.30 (0.19-0.42) cases/100 (PYF) after March 1999 (P < .001). The incidence of all subtypes of NHL decreased significantly and most pronouncedly for PBL. Among patients who started HAART, the incidence of NHL decreased from 0.88 (0.60-1.16) within the first 12 months after starting HAART to 0.45 (0.31-0.60) cases/100 PYF after more than 24 months (P = .004). In an adjusted Cox model for patients on HAART, the latest CD4 cell count and plasma viral load were both significantly associated with diagnosis of NHL; the relative hazard was 1.39 (range, 1.14-1.69) per 50% lower CD4 cell count, and 1.51 (range, 1.21-1.88) per 1 log higher plasma viral load. In conclusion, the incidence of NHL among HIV-infected patients has decreased significantly after the introduction of HAART, and the decline was most pronounced for PBL. After starting HAART, patients with insufficient immunologic and virologic responses were at highest risk of NHL.

Definition of two distinct types of AIDS‐associated non‐Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)-infected person is an AIDS-defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV-infected persons, compared with patients who spontaneously develop NHL. A series of 41 consecutive patients with HIV-associated NHL treated at St Vincent's Hospital, Sydney, between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high-grade malignant lymphoma, small non-cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high-grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment. The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median = 18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS-defining illness. The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV-infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features.