HIV-associated Malignancies Research Articles

AIDS-Related Vs. Non-AIDS-Related Diffuse Large B-Cell Lymphoma. Analysis of the County Hospital AIDS Malignancy Project (CHAMP)

Introduction: Stroger Hospital of Cook County (CCH) and the Ruth M. Rothstein CORE Center (CC) are the largest health providers for HIV+ patients (pts) in Chicago and among the largest in the United States. Together, CCH and CC treat over 5,500 HIV+ individuals per year and 60 newly diagnosed HIV-associated cancers yearly. In addition, CCH is the largest safety net hospital in Illinois; in the calendar year 2010, it had over 32,000 outpatient hematology/oncology clinic visits. The County Hospital AIDS malignancy project (CHAMP) is a prospective database of all HIV-associated hematological malignancies from 1995 to present. Here we analyzed the demographic, histological, germinal center status, outcome data, and HIV characteristics of pts with AIDS-related diffuse large B-cell lymphoma (AR-DLBCL). As a control, we compared these data to DLBCL pts not infected with HIV, intra-institutionally instead of national historical controls to better understand the AR-DLBCL population of the inner-city, a mostly minority, and one of the largest growing HIV populations.Methods: We screened the CCH cancer registry from 2001 to 2014, and 240 non-HIV pts were identified to have DLBCL. We searched the CHAMP database for cases of DLBCL from the same period. From 196 lymphomas, 51 were identified. Only pts who had a confirmed pathology report as DLBCL were included in this study. We subsequently identified the HIV characteristics, overall survival (OS), and patient demographics for all pts. In addition to OS data in both cohorts, we compared outcomes based on chemotherapy, stage, germinal center (defined by the HANS algorithm), and IPI status.Statistics: Non-parametric Fisher's exact test was used to examine the difference in proportion of pts in both the HIV and non-HIV arm. Survival data were analyzed using Kaplan-Meier analysis and Cox Proportional Hazards model.Results: The M:F ratio was 7.5:1 in AR-DLBCL and 1.9:1 in the non-HIV cohort (P<0.001). The median CD4+ count for the HIV population was 107 cells/mm3. Patients with germinal center DLBCL had a median CD4+ count of 196 cells/mm3 vs. non-germinal of 87 cells/mm3. The racial composition of the 2 cohorts showed a significantly higher percentage of African-Americans (AA) in the HIV cohort, 51% vs. 35% in the non-HIV, (p<0.04) and no difference in Caucasian or Hispanic populations. The AR-DLBCL population was younger. Only 4% of the HIV pts were 60 years and older compared to 32% in the non-HIV cohort. The HIV positive pts tended to present with more advanced disease. Seventy two % vs. 53% in the non-HIV cohort presented with stage III/IV disease (p <0.01). Only 18% vs. 38% in the non-HIV cohort presented with stage I/II disease (p <0.006). Of pts tested, there were no differences in GC (68 (n=15) vs. 66% (n=77) or NGC (32 (n=7) vs. 34% (n=39)) between HIV and non-HIV cohorts. The OS of the AR-DLBCL at 5 years was 54% vs. 77% in the non-HIV cohort (p<0.003). However, since 2009, pts with AR-DLBCL have been treated with daEPOCHR (Sparano et al, Blood 2010) at CCH, and since then no difference in OS compared to the non-HIV cohort has been identified. At 5 year follow up, the OS of AR-DLBCL was 81% treated with daEPOCHR (n=11) vs. 77% (n=108) in the non-HIV population (p 0.081). Comparing survival between each cohort by stage there was a trend to poorer outcomes in the AR-DLBCL for stage III/IV disease, 58% vs. 75% 5-year survival (p 0.064). Similarly, there was little difference in comparing each cohort by IPI score due to the small number of pts in each IPI category in the HIV cohort.Conclusions: In assessing the cases of AR-DLBCL, it appears to be a disease of AA (51% vs. 35%) men (88% vs. 53%) compared to the non-HIV population at the same institution. But when compared to the general population of Chicago, where AA constitute only 33% of the population, the disparity is more pronounced. Patients are also younger, 4% vs. 32% over 60 years of age. In addition, the AR-DLBCL pts present with more advanced disease (72% vs. 53%). As a whole, the AR-DLBCL cohort had a poorer OS survival than the non-HIV population, at 5 years, 54% vs. 77%. Importantly, pts with AR-DLBCL had the same OS as the non-HIV cohort, 81% vs. 77%, with a 5 year follow up when treated with daEPOCHR despite HIV pts presenting with a higher stage. Thus, education and screening in the AA community is needed, as this is an AA male disease in the inner city. It is also clear that treatment with daEPOCHR should be the therapy of choice when treating AR-DLBCL. DisclosuresNo relevant conflicts of interest to declare.

Let's face it - 13 unusual causes of facial masses in children.

Facial swelling is commonly encountered in paediatric patients and is typically related to an underlying infection. The spectrum of possible causes, however, is wide, and includes traumatic, inflammatory, nutritional and neoplastic aetiologies. In this pictorial essay we present 13 examples of rare conditions selected from a total of 136 MRI examinations performed at our institution between April 2007 and May 2013. These include HIV-associated malignancies such as a case of plasmablastic lymphoma, parotid gland tumours including a parotid hamartoma, rare congenital lesions such as a thyroid fetiform teratoma, and infective lesions including tuberculosis of the mandible. In many cases, only minimal information could be gleaned from the literature, particularly with regard to imaging findings. An analysis of the spectrum of masses and specific clinical presentations allowed for the construction of a diagnostic flowchart which may serve to assist in unusual cases.Teaching Points• Facial swelling is commonly encountered in paediatrics, with a wide spectrum of possible aetiologies.• MRI is the favoured imaging modality for accurate assessment.• Facial swelling is typically infectious in nature, but includes various benign and malignant causes.• This pictorial essay presents 13 examples of rare conditions with corresponding imaging.

Oral Plasmablastic Lymphoma Associated With Aids

Non-Hodgkin's lymphoma (NHL) represents the second most common HIV-associated malignancy, occurring 60 times more at HIV-infected individuals than in the healthy population. Plasmablastic lymphoma (PL) is a rare form of NHL with plasma cell differentiation. A 33-year-old HIV-infected female presented a painless and locally ulcerated lesion located at the mandibular buccal and lingual vestibule, extending from the second right pre-molar to first right molar, which had appeared 20 days earlier. The teeth adjacent to the lesion showed severe mobility. A single submandibular lymph node was increased in size. The patient reported having stopped her antiretroviral therapy for the last 4 months, because of nausea. An incisional biopsy of the intraoral mass was performed, and the histopathological examination revealed dense tissue infiltration by large neoplastic plasma cells. Immunohistochemistry findings were consistent with a PL. The patient restarted antiretroviral therapy and was submitted to CHOP chemotherapy. After 6 months of follow-up, there was regression of the lesion.

Diagnostic challenges of oral and cutaneous Kaposi's sarcoma in resource-constrained settings.

Kaposi's sarcoma (KS), caused by HHV-8, is the most frequent HIV-associated malignancy worldwide and remains a major scourge in Sub-Saharan Africa. KS is also endemic in much of Africa. There is a risk of misdiagnosis based solely on clinical appearance and haematoxylin and eosin (H&E) staining, especially with other reactive and neoplastic vascular proliferations which occur in the mouth. This study examined oral and cutaneous biopsies from clinically diagnosed lesions of KS in Kenya, using histopathology supplemented with immunohistochemistry (IHC) and polymerase chain reaction (PCR) for HHV-8 as confirmation of diagnosis. Biopsies of 49 lesions (28 oral, 21 cutaneous) previously diagnosed as 'KS' were re-examined by H&E staining and IHC targeting HHV-8 LANA-1. Positive controls were sections from embedded BCBL-1 cell lines. Negative controls were from three different HHV-8-negative biopsies. Confirmation of HHV-8 immunohistochemistry was sought by PCR and by determining the HHV-8 ORFK1 subtype. Whilst most cases were confirmed, 12 oral and 4 cutaneous lesions displayed clinical and histological features of KS but were negative to HHV-8 IHC. These oral lesions were re-diagnosed as pyogenic granulomata (n = 6), deep mycosis (n = 1), inflamed mucosa (n = 2) or 'uncertain but not KS' (n = 3). Whilst PCR is usually helpful in differentiating HHV-8 disease, all samples were HHV-8 PCR positive, with identical sequences, suggesting cross-contamination of samples in the original pathology laboratories. HHV-8 IHC is essential for the correct diagnosis of KS, but due to the high level of contamination in resource-poor settings, PCR is inadvisable.

Challenges in the detection, prevention, and treatment of HIV-associated malignancies in low- and middle-income countries in Africa.

Cancers associated with immunosuppression and infections have long been recognized as a major complication of HIV/AIDS. More recently, persons living with HIV are increasingly diagnosed with a wider spectrum of HIV-associated malignancies (HIVAM) as they live longer on combination antiretroviral therapy. This has spurred research to characterize the epidemiology and determine the optimal management of HIVAM with a focus on low-and middle-income countries (LMICs). Given background coinfections, environmental exposures, host genetic profiles, antiretroviral therapy usage, and varying capacities for early diagnosis and treatment, one can expect the biology of cancers in HIV-infected persons in LMICs to have a significant impact on chronic HIV care, as is now the case in high-income countries. Thus, new strategies must be developed to effectively prevent, diagnose, and treat HIVAM in LMICs; provide physical/clinical infrastructures; train the cancer and HIV workforce; and expand research capacity-particularly given the challenges posed by the limitations on available transportation and financial resources and the population's general rural concentration. Opportunities exist to extend resources supported by the President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis, and Malaria to improve the health-care infrastructure and train the personnel required to prevent and manage cancers in persons living with HIV. These HIV chronic care infrastructures could also serve cancer patients regardless of their HIV status, facilitating long-term care and treatment for persons who do not live near cancer centers, so that they receive the same degree of care as those receiving chronic HIV care today.

Short Communication: Genital Tumor Growth Factor-β1 Levels in HIV-Infected Indian Women Are Associated with Reduced Levels of Innate Antimicrobial Products and Increased HIV Shedding

Tumor growth factor (TGF)-β1 is a cytokine with potent immunoinhibitory functions and is known to be secreted by vaginal epithelial cells. The present study was designed to determine the association of cervicovaginal levels of TGF- β1 with various innate immune secretions such as cytokines and antimicrobial polypeptides [Trappin-2/Elafin and secretory leukocyte protease inhibitor (SLPI)] and cervical HIV shedding in HIV-infected Indian women. TGF- β1, antimicrobial polypeptides, and cytokine levels were estimated in the cervicovaginal lavages (CVLs) of 36 age-matched HIV-infected and 31 HIV-uninfected asymptomatic Indian women using an ELISA and Bio-Plex Assay, respectively. The nonparametric Mann-Whitney test and Spearman's test were used to compare the levels from both the groups and to determine the association of the TGF-β1 levels with cervical viral shedding and antimicrobial peptides. The levels of Trappin-2/Elafin and SLPI were similar in the CVLs of HIV-infected and HIV-uninfected women, but were significantly associated with a low cervical viral load (r=-0.501, p=0.005 for Trappin-2/Elafin and r=-0.488, p=0.007 for SLPI). Eleven (30.5%) of the 36 HIV-infected women showed 5- to 30-fold higher levels of TGF-β1 as compared to the levels in uninfected women. The TGF-β1 levels were significantly associated with higher cervical viral load (r=0.425, p=0.03) and with lower levels of Trappin-2/Elafin (r=-0.407, p=0.03) and SLPI (r=-0.405, p=0.04). The findings indicate a possible interdependent mechanism driving the identified higher TGF-β1 and lower antimicrobial peptide (Trappin-2/Elafin and SLPI) levels at the genital mucosa surface in HIV-infected women. We postulate that a combination of increased TGF-β1 secretion and altered levels of Trappin-2/Elafin and SLPI contributes to increased HIV shedding. The observation warrants further studies to identify the underlying mechanisms linking increased mucosal TGF-β1 levels and genital HIV shedding. Considering the known association of HIV and cervical cancers, it will also be important to assess the predictive capacity of TGF-β1 levels in HIV-associated cervical malignancies.

Malignancies in South African Children With HIV

In 2008 the South African Children's Cancer Study Group decided to review the epidemiology, management, and chemotherapy response of HIV-positive children with malignancy. This is a retrospective analysis of data collected from the records of HIV-positive children diagnosed with malignancy at 7 university-based pediatric oncology units serving 8 of the 9 provinces in South Africa. Two hundred eighty-eight HIV-positive children were diagnosed with 289 malignancies between 1995 and 2009. Age at diagnosis ranged from 17 days to 18.64 years; median 5.79 years. Of the 220 HIV-associated malignancies, there were 97 Kaposi sarcomas, 61 Burkitt lymphomas, 47 other B-cell lymphomas including 2 primary central nervous system lymphomas, 12 Hodgkin lymphomas, and 3 leiomyosarcomas. Sixty-nine patients presented with non-AIDS-defining malignancies. More than 80% presented with advanced disease. Most patients (76.7%) were naive to antiretroviral therapy; 22.2% did not have access because it only became available in public hospitals in 2004. One hundred ninety-seven children were treated with curative intent; 91 received palliative care due to advanced malignancy and/or advanced HIV disease. Nearly one third had coexisting pathology, mostly tuberculosis. Overall survival for the whole group was 33.7%, but was 57.8% for those treated with antiretroviral therapy and chemotherapy. The study shows more Kaposi sarcoma and fewer primary central nervous system lymphomas among HIV-positive children than that is reported in the developed world, but confirms a higher incidence of non-Burkitt B-cell lymphoma than in HIV-negative children. The high number of non-AIDS-defining malignancies underscores the prevalence of HIV-AIDS in South Africa. The overall survival should improve with universal access to antiretrovirals and earlier diagnosis.

British HIV Association guidelines for HIV‐associated malignancies 2014

<scp>B</scp>ritish <scp>HIV</scp> Association guidelines for <scp>HIV</scp>‐associated malignancies 2014

Developing Clinical Strength-of-Evidence Approach to Define HIV-Associated Malignancies for Cancer Registration in Kenya

BackgroundSub-Saharan Africa cancer registries are beset by an increasing cancer burden further exacerbated by the AIDS epidemic where there are limited capabilities for cancer-AIDS match co-registration. We undertook a pilot study based on a “strength-of-evidence” approach using clinical data that is abstracted at the time of cancer registration for purposes of linking cancer diagnosis to AIDS diagnosis.Methods/FindingsThe standard Nairobi Cancer Registry form was modified for registrars to abstract the following clinical data from medical records regarding HIV infection/AIDS in a hierarchal approach at time of cancer registration from highest-to-lowest strength-of-evidence: 1) documentation of positive HIV serology; 2) antiretroviral drug prescription; 3) CD4+ lymphocyte count; and 4) WHO HIV clinical stage or immune suppression syndrome (ISS), which is Kenyan terminology for AIDS. Between August 1 and October 31, 2011 a total of 1,200 cancer cases were registered. Of these, 171 cases (14.3%) met clinical strength-of-evidence criteria for association with HIV infection/AIDS; 69% (118 cases were tumor types with known HIV association – Kaposi’s sarcoma, cervical cancer, non-Hodgkin’s and Hodgkin’s lymphoma, and conjunctiva carcinoma) and 31% (53) were consistent with non-AIDS defining cancers. Verifiable positive HIV serology was identified in 47 (27%) cases for an absolute seroprevalence rate of 4% among the cancer registered cases with an upper boundary of 14% among those meeting at least one of strength-of-evidence criteria.Conclusions/SignificanceThis pilot demonstration of a hierarchal, clinical strength-of-evidence approach for cancer-AIDS registration in Kenya establishes feasibility, is readily adaptable, pragmatic, and does not require additional resources for critically under staffed cancer registries. Cancer is an emerging public health challenge, and African nations need to develop well designed population-based studies in order to better define the impact and spectrum of malignant disease in the backdrop of HIV infection.

Biomarkers of HIV-associated Cancer.

Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.

Broader Implications of a Stage-Guided Stratified Therapeutic Approach for AIDS-Related Kaposi's Sarcoma

Kaposi sarcoma (KS) remains the most common illness in people living with HIV (PLWH), although its incidence has declined dramatically since the introduction of combination antiretroviral therapy (cART). Unlike most malignancies that are staged using the TNM system, which takes into account tumor size and extent of spread, staging for AIDS-related KS must account for the presence of other AIDS-related effects, such as the severity of immunosuppression and presence of opportunistic infections. The AIDS Clinical Trials Group (ACTG) staging system considers three factors, notably, the extent of the tumor (T), the status of the immune system as measured by the CD4 count (I), and the extent of systemic illness. Each factor is further subgrouped into either good risk (0) or poor risk. T0 disease is defined as KS that is limited to the skin but without edema or ulceration, lymph node disease, or flat palatal lesions. T1 disease is defined as the presence of tumor-associated edema or ulceration, or extensive oral/GI KS or other non-nodal visceral lesions. Although this system has helped to clinically categorize patients, until now there has been no clear, universally adopted treatment algorithm that is based on disease stage. As with other HIV-associated malignancies, the challenge for health care professionals treating AIDS-related KS has revolved around the ability to effectively treat without causing the patient further immunocompromise and, if possible, to concomitantly reconstitute the immune system. Therefore, it is not surprising that the introduction of cART has led to a remarkable improvement in median overall survival (OS) of affected patients, which was less than 18 months in the pre-cART era. In addition to improving prognosis and time to disease progression in KS, cART can lead to lesion regression, and this applies to both protease inhibitor and non-nucleoside reverse transcriptase inhibitor– based regimens, the major categories of antiretroviral regimens. However, the resolution of KS with cART usually follows the recovery of cellmediated immunity in the host and can therefore be a slow process over several months, complicated in some instances, for example, by an immune reconstitution inflammatory syndrome. Furthermore, there is the complex paradox of how best to treat patients already receiving cART who have maintained a high CD4 count and low viral load, but who still develop KS. In the pre-cART era, chemotherapy was the mainstay of treatment for suitable patients with AIDS-related KS, and this has remained the major therapeutic modality despite the advent of cART in 1996. In the pre-cART era, chemotherapy was adopted as an accepted treatment modality in AIDS-related KS on the basis of the results of a number of clinical trials that assessed the efficacy and safety of combination regimens. In one study, 18 consecutive patients with socalled disseminated KS received a six-drug regimen of doxorubicin, vinblastine, bleomycin (ABV), dactinomycin, vincristine, and dacarbazine, with a partial or complete response observed in 13 individuals. Opportunistic infections were the most common cause of death. Another study compared the use of recombinant interferon alpha or ABV/dactinomycin, vincristine, and dacarbazine in the 18 consecutive patients with disseminated disease, and responses were similar in the two groups and were comparable with the results of earlier trials. Subsequent studies in the preand post-cART era have provided strong evidence in support of the use of single-agent anthracyclines or taxanes, particularly pegylated liposomal doxorubicin (PLD) and paclitaxel. In a study reported in 1998, Northfelt et al randomly assigned 258 patients with advanced AIDS-related KS to receive either PLD (20 mg/m) or ABV every 14 days for six cycles. PLD was more effective and less toxic than ABV (overall response rates, 45.9% v 24.8%; P .001). In 2010, Cianfrocca et al reported a study comparing paclitaxel with PLD in patients with advanced AIDS-related KS and demonstrated comparable response rates (56% v 46%; P .49), median progression-free survival of 17.5 v 12.2 months (P .66), and 2-year survival rates of 79% v 78% (P .75), although paclitaxel was associated with more grade 3 to 5 toxicity (84% v 66%; P .077). PLD has thus become the current standard first-line therapy for advanced disease in many centers in the developed world, with paclitaxel reserved as a second-line agent. However, this is not the case in less developed countries, where HIV remains endemic. Given the complexity of the ACTG staging system, there is no clear international consensus on what constitutes advanced disease, and therefore, no clear algorithm exists to determine which patients should receive cART alone and which should receive cART plus chemotherapy, or chemotherapy alone, given that interactions between protease inhibitors and chemotherapy may lead to worse neutropenia. In the article that accompanies this editorial, Bower et al answer these issues in part for the first time and present an elegantly JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 5 FEBRUARY 1

Update on the treatment of HIV-associated hematologic malignancies

HIV is associated with an excess cancer risk, particularly of lymphoid malignancies. Modern therapeutics has changed the landscape of HIV disease and typical opportunistic complications of AIDS are now largely avoided. Although the risk of lymphoma has decreased, it still remains high. Nevertheless, treatment outcomes have improved due both to improvements in HIV medicine and in cancer therapeutics for the common lymphomas occurring in those with HIV infection. Other hematologic malignancies are rarely seen in HIV-infected patients, but the standardized risk ratio for many of these cancers is higher than in the background population. Principles of cancer care and appreciation for HIV infection as a comorbid condition can guide physicians in setting realistic goals and treatment for this patient population. In many cases, expected outcomes are very similar to the HIV-unrelated patients and therapeutic planning should be based on this understanding. Treatment tolerance can be predicted based on the status of the HIV disease and the cancer therapy being administered. For those hematologic cancers in which transplantation is part of standard care, this modality should be considered an option in those with HIV infection.

Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention

The development of HIV protease inhibitors more than two decades ago heralded a new era in HIV care, changing the infection from universally fatal to chronic but controllable. With the widespread use of protease inhibitors, there was a reduction in the incidence and mortality of HIV-associated malignancies. Studies later found these drugs to have promising direct antitumor effects. Protease inhibitors have a wide range of effects on several cellular pathways that are important for tumorigenesis and independent of inhibition of the HIV protease, including reducing angiogenesis and cell invasion, inhibition of the Akt pathway, induction of autophagy, and promotion of apoptosis. Among protease inhibitors, nelfinavir appears to have the most potent and broad antineoplastic activities, and also affects replication of the oncogenic herpesviruses Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus. Nelfinavir is being studied for the prevention and treatment of a wide range of malignancies in persons with and without HIV infection. Nelfinavir and other protease inhibitors are well tolerated, oral drugs that have promising antitumor properties, and may prove to play an important role in the prevention and treatment of several cancers. Additional insights into protease inhibitors' mechanisms of action may lead to the development of novel cancer chemotherapy agents.

Adverse events in non-AIDS-defining cancer patients receiving chemotherapy and combined antiretroviral therapy.

e12523 Background: From 1991 to 2005, the number of cases of non-AIDS defining cancers (NADC) rose from 3,192 to 10,059 in the USA. Studies have shown an improvement in survival for many HIV-associated malignancies in the post HAART era. Drug-drug interactions between HIV therapy and chemotherapy (CTX) are not well understood. HIV medications can inhibit or induce the cytochrome p450 system, modulating CTX clearance. To understand CTX-HIV medication interactions, we performed a retrospective analysis of all patients (pts) diagnosed with a solid NADC who took CTX with combined antiretroviral therapy (cART). Methods: 157 pts with solid NADC were identified via a computer search at County Hospital. Adverse events (AE) during CTX in pts taking cART were assessed by chart review and graded per the NCI Common Terminology Criteria. Statistics: A Fisher's exact test was used to examine the differences in AE incidence. Results: Patients who did not take cART in conjunction with, or did not require CTX, were excluded. The number of pts analyzed for anal cancer (n=25), lung carcinoma (n=9), breast (n=7), and head and neck carcinoma (HNSCC) (n=4) represents 94% of pts taking cART with CTX in our cohort. Interestingly, Forty-two pts (50%) never received cART during therapy. All pts with anal carcinoma were treated with mitomycin/5FU/radiotherapy. 46 % of the patients taking ritonavir-based cART (6 pts of 13) developed a G4 neutropenia versus 8% (1 pt of 12) taking non-ritonavir cART (p&lt;0.07). Anemia all grades with ritonavir, 54%, versus non-ritonavir cART 16% (p&lt;0.09). All grades neutropenia for lung carcinoma while taking ritonavir was 83% versus 33% while taking non-ritonavir cART. No other correlations were identified. In this cohort, 17 pts received platinum (37%), taxanes (n=5) (11%), anthracyclines (n=5) 11%, gemcitabine (n=2) (4%), and pemetrexed (n=1). No difference in AE was noted between any CTX class, AE, and cART. Conclusions: Ritonavirinduced a 38% increase in G4 neutropenia and anemia during treatment of anal carcinoma with mitomycin/5FU. More trials including HIV-associated cancer pts are needed to assess the role of cART when given in conjunction with CTX.

Use of CXCR4-antagonist for haematopoietic stem cell mobilization in HIV-infected patients with haematological malignancies

Use of CXCR4-antagonist for haematopoietic stem cell mobilization in HIV-infected patients with haematological malignancies

Clinical characteristics and outcomes of HIV‐infected children diagnosed with kaposi sarcoma in malawi and botswana

Kaposi sarcoma (KS) is the most common HIV-associated malignancy in sub-Saharan Africa. The presentation and outcomes of pediatric KS are not well understood. We performed a retrospective cohort analysis of 81 HIV-infected children with KS at the Baylor Children's Clinical Centres of Excellence in Malawi and Botswana from March 2003 to October 2009. Eighty-one children with KS were identified whose median age was 8.0 (inter-quartile range 5.1-11.3) years. KS lesions were presented primarily on the skin (83%), lymph nodes (52%), and oral mucosa (41%). Occasionally disease was limited to the lymph nodes only (10%). Severe immunosuppression (70%), anemia (29%), and thrombocytopenia (17%) were common laboratory findings. Highly active antiretroviral therapy (HAART) was administered to 94% of children, including 77% who received HAART plus chemotherapy. KS immune reconstitution inflammatory syndrome (IRIS) occurred in 22%. Disease status 12 months after KS diagnosis was determined for 69 children: 43% were alive and 57% had died. Severe immunosuppression was independently associated with mortality in multivariate analysis (OR = 4.3; 95% CI 1.3-14.6; P = 0.02). KS occurs in a significant number of HIV infected children in sub-Saharan Africa. Pediatric KS is distinct from KS in adults. Lymph node involvement was a common manifestation of KS in children, and severe immunosuppression was associated with the highest mortality risk. Though overall mortality was high in children with KS, patients did achieve clinical remission in settings with limited diagnostic and therapeutic resources.

Epidemiological surveillance of the HIV/AIDS complex through the analysis of trends in the incidence of Kaposi’s sarcoma in Cali, Colombia

The Kaposi's sarcoma (KS) incidence has markedly changed in the general population since the onset of the AIDS epidemic in the eighties and after the introduction of the Highly Active Antiretroviral Therapy (HAART) in the nineties. To investigate incidence rate trends for Kaposi's sarcoma before and during the (HIV/AIDS) epidemic in Cali, Colombia. Exploratory ecological study that included all Kaposi's sarcoma cases identified by the Cali Cancer Registry from 1962-2007, and 12,887 cases of HIV/AIDS recorded in the Municipal Health Secretariat of Cali between 1986 and 2010. The joinpoint regression model was used to conduct the incidence rate analyses between the years 1962 and 2010. A total of 349 KS cases were identified during the study period. Only 5.3% of the cases (n=20) were diagnosed in the pre-epidemic era (1963-1987), of these, 35% were women, and 90% of the tumors were located on the skin. In contrast, 94.7% of KS cases (n=329) were discovered after the emergence of HIV-AIDS. There was a significant decrease in the proportion of women (10.9%, p <0.001) and an increase in the frequency of tumors with an extra-cutaneous location (19.1%, p <0.01) compared to those cases diagnosed in the pre-epidemic era. Notification rates of HIV/AIDS have decreased since 2002 in both genders but KS incidence rates have decreased since 2004 in men only. The downward trend in the incidence of these diseases may be associated with factors that prevent the transmission of HIV infection or limit the spread of HIV in the community. Cancer registries represent a resource for timely, population-based surveil-lance of HIV-associated malignancies in Cali, Colombia.

Abstract CN01-02: Epidemiology and pathogenesis of cancer in the setting of HIV infection

Abstract Cancer has emerged as a leading cause of morbidity and mortality among HIV-infected persons worldwide. The incidence of cancer is increased exponentially in HIV-positive individuals, and in the United States it is estimated that nearly 10% of persons living with HIV will develop cancer in their lifetime. In this presentation, the epidemiology of HIV-associated malignancies in resource-rich and resource-limited settings will be reviewed, and the factors that predispose persons living with HIV to the development of cancer will be explored. The translatability of cancer screening and prevention practices from HIV-negative to HIV-positive patient populations remains unproven, but strategies for cancer prevention in HIV-positive individuals will be reviewed. Citation Format: Corey Casper. Epidemiology and pathogenesis of cancer in the setting of HIV infection. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN01-02.

Management of HIV-Associated Hodgkin Lymphoma: How Far We Have Come

Although Hodgkin lymphoma (HL) is not considered an AIDSdefining malignancy, population-based studies have demonstrated an increased incidence of this disease in the setting of HIV infection. In a prospective cohort study of 11,112 individuals who were positive for HIV, with 71,687 patient-years of follow-up, the incidence of HL was 14 times higher than in the general population. In contrast to other HIV-associated malignancies that occur more commonly with severe immunocompromise, HL is associated with moderate immunologic impairment and the incidence actually seems to decline at CD4 lymphocyte counts of less than 200/ L. Although incidence rates for the AIDS-defining malignancies (Kaposi’s sarcoma, aggressive B-cell non-Hodgkin lymphoma [NHL]) have fallen, the incidence of HL may actually be increasing since the advent of combination antiretroviral therapy (cART), perhaps as a consequence of improvement in the level of immune function. However, the increased relative risk of HL is substantially lower than that observed for aggressive B-cell lymphoma. As a result of the small number of cases, studies investigating approaches to management of HIV-associated HL have been largely retrospective in design. For the more common AIDS-defining lymphomas, diffuse large B-cell lymphoma and Burkitt lymphoma, outcomes have improved dramatically in the 16 years since the introduction of active antiretroviral therapies, which have transformed HIV disease into a survivable chronic illness. Prospective studies in the pre-cART era demonstrated 2-year overall survival (OS) in the 10% to 20% range with complete remission (CR) rates of 35% to 50%, far inferior to those observed in non-HIV–associated lymphomas. Prognosis at that time was largely dependent on the severity of immunosuppression rather than on features of the lymphoma. This experience changed with the advent of cART such that now treatment outcomes using standard regimens such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab approach those observed in the non-HIV–infected population, with CR rates of 65% to 77% and 2-year OS rates of more than 60%. The International Prognostic Index (IPI) score seems to be a significant prognostic factor in patients treated with chemotherapy and concurrent cART. On the basis of the age-adjusted IPI score, the survival of patients in one trial using rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone was similar to that achieved by patients with aggressive lymphomas who were not infected with HIV. HL in the HIV-seropositive population is more likely to have mixed cellularity or lymphocyte-depleted histology and is almost always Epstein-Barr virus–associated. The majority of patients present with advanced-stage disease. Before the introduction of cART, treatment outcomes for HIV-HL were poor. In an Italian retrospective study of 114 patients with HIV-associated HL who received various standard chemotherapeutic regimens, the median OS was 15 months. Sixty percent died, 35% of those from opportunistic infection, 33% from HL, and 12% from both. As has been the case for aggressive B-cell lymphomas in patients with HIV infection, small retrospective and prospective studies have suggested improvement in outcome with the advent of cART. A retrospective study of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with cART in 62 patients with advanced-stage HIVassociated HL demonstrated a CR rate of 87% and 5-year OS of 76%. A prospective trial reported a CR rate of 81% and 2-year OS of 51% in 59 patients treated with the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) administered with antiretroviral therapy. The fact that only 10% of these patients received radiotherapy suggests that the regimen was either not delivered as designed or that the inclusion of patients with early-stage and low-bulk disease (factors associated with inferior outcome with this regimen) resulted in relatively disappointing outcomes. In the article that accompanies this editorial, the German HIV-Related Lymphoma Study Group presents data from the largest prospective trial ever conducted in patients with HIV-associated HL. In this study, 112 patients were allocated to treatment on the basis of stage and risk category. Those with early-stage favorable disease (IA/B or IIA/B) received two to four cycles of ABVD plus 30 Gy of involved-field radiotherapy. Patients with early-stage unfavorable disease received four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) at baseline or four cycles of ABVD followed by 30 Gy of involved-field radiotherapy if disease was 5 cm or residual disease was 2 cm. Those with advanced disease received eight cycles of BEACOPP with or without radiotherapy to sites 2.5 cm. Patients with advanced HIV disease, including Eastern Cooperative Oncology Group performance score 2, received ABVD. There were five toxic deaths: 4% with early favorable, 0% with early unfavorable, and 7% with advanced disease. CR rates were 96%, 100%, and 86% for these three groups, respectively, and 2-year PFS JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 33 NOVEMBER 2

P-0128 HIV-Associated Lymphoma of the Gastrointestinal Tract in the Combination Antiretroviral Therapy Era

ABSTRACT Introduction HIV-associated non-Hodgkin's lymphoma (NHL) remains the most common HIV-associated malignancy despite the advent of combination antiretroviral therapy (cART). The gastrointestinal (GI) tract is one of the most common extranodal sites. GI NHL can be divided into primary GI lymphoma and secondary involvement from diffuse nodal disease. The median survival time of HIV-associated lymphoma with GI tract involvement in the pre-cART era was 4–10 months. The aim of this study is to investigate its characteristics and survival outcomes in the cART era. Methods We retrospectively analyzed the medical records of patients (including 2023 HIV-infected patients) diagnosed with GI lymphoma between April 2000 and December 2011 at Osaka National Hospital. Results Seventy-four patients had been diagnosed with GI lymphoma (primary or systemic lymphoma with GI involvement) with (14 patients) or without (60 patients) HIV infection. Of the 2023 HIV-infected patients, 14 had been diagnosed with GI lymphoma. One of these patients had been diagnosed with primary gastric diffuse large B-cell lymphoma (DLBCL) on autopsy. Of the 13 patients, 5 had primary GI lymphoma and 8 had systemic lymphoma with GI tract involvement. The median age at presentation was 44 years (range, 32–72 years), median CD4 lymphocyte count was 101/mm3 (range, 4–560/mm3), and median HIV RNA viral load was 52000 copies (range, Conclusion In HIV-associated lymphoma with GI tract involvement, survival is better in the cART era than the pre-cART era. The overall survival of HIV-infected patients with GI aggressive B-cell lymphomas was similar to that of HIV-negative patients with such lymphomas.