HIV-associated non-Hodgkin Lymphoma Research Articles

A retrospective cohort study describing chemotherapy-induced peripheral neuropathy in Non-Hodgkin lymphoma patients treated with EPOCH ± R: does HIV status matter?

The frontline immuno-chemotherapy regimen for HIV-associated non-Hodgkin Lymphoma is dose-adjusted EPOCH ± R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). Chemotherapy-induced peripheral neuropathy (CIPN), caused by vincristine, is a common adverse effect of EPOCH ± R, negatively impacting long-term patient outcomes. The primary objective of this study was to determine the incidence of CIPN, stratified by HIV status, in patients treated with EPOCH ± R. A retrospective cohort study at a tertiary referral comprehensive cancer center evaluated patients treated with EPOCH ± R from 2011 to 2018. The final sample included 27 patients with HIV compared to 279 without HIV (total n = 306). Overall, the incidence of CIPN was 29.4% (n = 90), including 5 with HIV (18.5%) and 85 without HIV (30.5%). Propensity scores were used to match patients by HIV status. Although no relationship was found between HIV status and neuropathy, CIPN affects too many undergoing treatments for lymphoma, supporting future investigations to minimize toxicities.

Estimates of the global burden of non-Hodgkin lymphoma attributable to HIV: a population attributable modeling study

Human immunodeficiency virus (HIV) significantly increases the risk of non-Hodgkin lymphoma (NHL) development, yet the population-level impact on NHL burden is unquantified. We aim to quantify this association and estimate the global burden of HIV-associated NHL. In this meta-analysis, we searched five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) from database inception up to September 13, 2023, identifying cohort, case-control, or cross-sectional studies with an effective control group to assess NHL risk among individuals with HIV infection, with two authors extracting summary data from reports. Global and regional HIV-associated population attributable fraction (PAF) and NHL disease burden were calculated based on the pooled risk ratio (RR). HIV prevalence and NHL incidence were obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Trends in NHL incidence due to HIV were assessed using age-standardised incidence rate (ASIR) and estimated annual percentage change (EAPC). This study was registered with PROSPERO (CRD42023404150). Out of 14,929 literature sources, 39 articles met our inclusion criteria. The risk of NHL was significantly increased in the population living with HIV (pooled RR 23.51, 95% CI 17.62-31.37; I2=100%, p<0.0001), without publication bias. Globally, 6.92% (95% CI 2.18%-11.57%) of NHL new cases in 2019 were attributable to HIV infection (30,503, 95% CI 9585-52,209), which marked a more than three-fold increase from 1990 (8340, 95% CI 3346-13,799). The UNAIDS region of Eastern and Southern Africa was the highest affected region, with 44.46% (95% CI 19.62%-58.57%) of NHL new cases attributed to HIV infection. The Eastern Europe and Central Asia region experienced the highest increase in ASIR of NHL due to HIV in the past thirty years, wherein the EAPC was 8.74% (95% CI 7.66%-9.84%), from 2010 to2019. People with HIV infection face a significantly increased risk of NHL. Targeted prevention and control policies are especially crucial for countries in Eastern and Southern Africa, Eastern Europe and Central Asia, to achieve the UNAIDS's '90-90-90' Fast-Track targets. Limited studies across diverse regions and heterogeneity between research have hindered precise estimations for specific periods and regions. Sichuan Provincial People's Hospital, Chengdu, China; Health Care for Cadres of Sichuan Province, Chengdu, China; Science and Technology Department of Sichuan Province, Chengdu, China.

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Treatment Outcomes and Prognostic Factors in 40 Patients with Primary Effusion Lymphoma

Background: Primary effusion lymphoma (PEL) is a rare, B cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, that is strongly associated with HIV infection. PEL often presents as malignant body cavity effusions but can also present as extracavitary masses. Patients may also have concurrent Kaposi sarcoma (KS) or multicentric Castleman disease (MCD). 80% of PEL is also positive for EBV, and in a cohort of 20 patients we previously showed EBV + PEL had improved overall survival (OS) (Lurain et al. Blood 2019). PEL prognosis is poor compared to other HIV-associated NHL with median survival of 6-10 months. While patients are often treated with chemotherapy regimens used in other NHL, the optimal front-line and subsequent-line treatments are unknown. In this largest cohort of patients with PEL in the United States, we evaluated survival, prognostic markers, and second-line treatments in relapsed/refractory disease.Methods: We analyzed clinical records of all patients with PEL treated in the HIV and AIDS Malignancy Branch at the National Cancer Institute from 2000-2021. We collected demographics, disease characteristics, concurrent KS and MCD, EBV status of tumor by EBER staining, and laboratory data at diagnosis as well as at progression and subsequent lines of therapy. We calculated overall survival (OS) of all patients and progression-free survival (PFS) in those who received front-line EPOCH by Kaplan-Meier method. The survival of extracavitary vs. cavitary PEL was compared using an exact log-rank test. A univariate Cox proportional hazard model was performed to determine prognostic variables associated with OS.Results: We identified 40 patients with PEL: 38 cisgender men, 2 cisgender women; 18 non-Hispanic Black, 6 Hispanic, 16 non-Hispanic White; median age 41 years. At diagnosis of PEL, 29 patients had concurrent KS, and 7 had concurrent MCD. Eight patients had only extracavitary disease, and 5 had leptomeningeal disease. All but 1 had HIV, and all with HIV received antiretroviral therapy. At diagnosis, median HIV viral load (VL) was 50 (IQR: 27-8323) copies/mL, median CD4 + cell count was 100 (IQR:44-395) cells/µL, and median KSHV VL was 4147 copies/10 6 cells (IQR:178-68,526). One patient died prior to receiving treatment. Of the 39 patients who received front-line treatment, 38 received combination chemotherapy (EPOCH [36], CHOP [1], ICE [1]) with rituximab added in 34 patients to treat concurrent MCD or deplete the KSHV-infected B cell reservoir. One patient received pembrolizumab as up-front therapy due to concurrent progressive multifocal leukoencephalopathy. Twenty-three (57%) had complete remission (CR) by Lugano criteria. Median PFS after front-line EPOCH was 16.4 months (Figure 1a), and median OS in all patients was 35.6 months (Figure 1b), with 5-year OS of 44%. Median OS for patients with extracavitary disease was significantly higher than in patients with cavitary disease (p=0.023, Figure 1c). EBER-positive tumors (HR=0.21, p=0.005) were associated with improved survival, while concurrent KS, MCD, leptomeningeal disease, and baseline CD4 and KSHV VL were not associated with OS outcomes.Eleven patients with relapsed/refractory disease received second-line therapy, including combination chemotherapy (3); brentuximab (3); pembrolizumab (1); pembrolizumab and pomalidomide (1); interferon-alpha, ganciclovir, and bevacizumab (1); bortezomib, ganciclovir, and zidovudine (1); and radiation to pelvic lymph nodes (1). Five of these patients received subsequent treatment after disease progression, including 2 patients with leptomeningeal PEL, 1 who received daratumumab and 1 who received pomalidomide and pembrolizumab with ongoing CRs at 12 months and 33 months, respectively.Conclusion: Patients with PEL had a median OS of 35.6 months, which is improved from previous reports. Patients with extracavitary PEL appear to have improved OS, and we confirmed our prior study noting EBER-positive PEL is a positive prognostic marker. Promising chemotherapy-sparing treatment regimens in relapsed/refractory PEL, include pembrolizumab, pomalidomide, and daratumumab. [Display omitted] DisclosuresUldrick: Regeneron: Current Employment; Roche: Research Funding; Merck: Other: Receives study drug; Celgene: Research Funding. Yarchoan: Celgene: Research Funding; Merck: Other: Clinical Trial Support; EMD-Serano: Other: Clinical Trial Support; Eli Lilly: Other: Clinical Trial Support; CTI BioPharma: Other: Clinical Trial Support; Janssen Pharmaceuticals: Other: Clinical Trial Support; U.S. Dept of Health and Human Services: Patents & Royalties. Lurain: EMD-Serrono: Research Funding; BMS-Celgene: Research Funding; CTI Biopharma: Research Funding; Merck: Research Funding; Janssen: Research Funding.

Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial)

AbstractEPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.

Tumor lysis syndrome as a risk factor for very early mortality in HIV-associated non-Hodgkin's lymphoma: A 10-year single-center experience.

Despite the effectiveness of combination antiretroviral therapy, persons living with human immunodeficiency virus (PLWHIV) remain at a high risk of developing non-Hodgkin lymphoma (NHL). We aimed to analyze the demographics and outcomes of the HIV-associated NHLs. Between 2005 and 2014, PLWHIV with NHLs were retrospectively enrolled at a tertiary referral center. Characteristics and survival were reviewed and analyzed. Twenty-two HIV-associated NHLs were identified, with a median follow-up of 14 months (range, 0.1-139.7), including eight diffuse large B-cell lymphomas (DLBCLs), eight primary central nervous system lymphomas (PCNSLs), and six Burkitt's lymphomas (BLs). Nine patients (40.9%) were diagnosed with NHLs and HIV infection concurrently. The prognosis of DLBCL patients tended to be better prognosis than that of BL and PCNSL patients (median overall survival: not reached vs. 3.5 months, p = 0.056). Very early mortality (death within 14 days after NHL diagnosis) was noted in five patients (22.7%), and tumor lysis syndrome (TLS) is a predictive factor for very early mortality among PLWHIV (hazard ratio:11.3, 95% confidence interval: 1.1-114.4, p = 0.04). Management of the early treatment phase of HIV-associated NHLs remains a major challenge. Careful intervention to patients with TLS might be the key to improve treatment outcomes.

Response-Adapted Therapy with Infusional EPOCH Chemotherapy Plus Rituximab in HIV-Associated, B-Cell Non-Hodgkin's Lymphoma

Introduction: Six cycles of rituximab plus infusional EPOCH is considered a preferred regimen for first-line treatment of HIV-associated diffuse large B-cell lymphoma (DLBCL), HHV8-positive DLBCL, and primary effusion lymphoma, and is among the preferred regimens for HIV-associated Burkitt's lymphoma in the 2019 NCCN guidelines. A phase III trial demonstrated non-inferiority of 4 cycles of R-CHOP (followed by 2 additional doses of rituximab) compared with 6 cycles of R-CHOP in immunocompetent patients with low-risk DLBCL (stage I-II, age 18-60 years, and an age-adjusted International Prognostic Index score of 0), indicating that de-escalation of treatment duration may be safely achieved without compromising curability in an appropriately selected patient population. Here we report the outcomes for patients with HIV-associated DLBCL and high-grade non-Hodgkin lymphoma (NHL) treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy under a completed prospective clinical trial (AMC-034). Methods: One hundred-six patients with HIV-associated DLBCL or high-grade CD20-positive NHL enrolled at multiple centers across the U.S. were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of dose-adjusted EPOCH regimen tailored for HIV+ patients. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. Results: Sixty-four of 106 patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms; characteristics of entire population and CR proportions stratified by number of EPOCH treatment cycles were similar (Table 1).The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) due to failure to achieve a CR after 2 cycles (Table 2 and Figure 1). Time to disease progression and overall survival wer also similar for those treated with 4 or fewer cycles compared with 5-6 cycles (91% vs. 87%, and 78% vs. 90%, respectively) (Table 2 and Figure 1). Conclusion: A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in an appropriately selected population of patients with HIV-associated NHL, which merits further evaluation in additional prospective trials. Disclosures Noy: Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding.

HIV-Related Primary Diffuse Large B Cell Lymphoma of the Appendix. What Can We Learn?

BACKGROUNDThe introduction of antiretroviral therapies has decreased the incidence of HIV associated Non Hodgkin's Lymphoma (NHL), and the median CD4 count on diagnosis has increased; however, the overall aggressive nature of HIV associated NHL has not changed. The gastrointestinal tract is the most common location for extranodal lymphomas, but primary appendiceal lymphoma (PAL) is extremely rare and represents only 0.015% of all gastrointestinal lymphomas. There is limited data on management of these patients; therefore, herein we present a review of the available literature along with our own, and first reported case to our knowledge, of HIV associated Primary Diffuse large B-cell lymphoma (DLBCL) of the appendix . METHODSWe did a detailed literature review using the PubMed and MEDLINE database for published cases of primary appendiceal lymphoma from 1973 to 2018 and found only 125 cases of PAL. We decided to exclude the following histologies due to their significantly different prognosis and management: mucosa-associated lymphoid tissue, Hodgkin's lymphoma and extraosseous plasmacytomas. Demographics (age, gender), tumor histology and clinical characteristics (presentation and management) were assessed. All patients with appendiceal lymphoma were categorized using the 2016 WHO classification of mature lymphoid neoplasms. This was in response to a case encountered at our institute where a 38-year-old woman with controlled HIV presented with right iliac fossa pain and findings of appendicitis found to have DLBCL in the appendix.RESULTS AND DISCUSSIONPAL primarily afflicts males, the mean age has been shown to be around 54 years (range: 40-62 years) and usually presents clinically as appendicitis. Out of the total 125 cases of PAL reviewed, the most common histological type was DLBCL (34.4%- 43 cases) followed by Burkitt's (27.2%-34 cases). None of them have been reported as HIV associated.Our patient had the classic presentation of acute appendicitis (by clinical signs/symptoms and by imaging) and diagnosis was made post operatively. Our patient was 38 years old which is significantly younger than the expected range. The optimal treatment for intestinal lymphomas, let alone appendiceal lymphomas, has not been established yet. Most cases previously reported received appendectomy with adjuvant chemotherapy and had no disease recurrence at reported follow-up times. Our patient presented emergently with appendicitis and therefore underwent surgical resection prior to diagnosis of lymphoma, we then elected to proceed with adjuvant EPOCH-R based on efficacy data in the HIV population as per Sparano group. She had no evidence of disease elsewhere and has tolerated the chemo-immunotherapy selected with minimal hematologic toxicities, as expected.CONCLUSIONWe describe here a rare case of primary appendiceal lymphoma in a young patient with underlying HIV infection. Treatment of patients like ours is very challenging as there are no prior reported cases of HIV associated PAL and therefore no standard guidelines. There is limited data for PAL in general and further studies are required to determine natural course of disease and appropriate treatment protocols. After multidisciplinary discussion and review of limited literature decision was made to proceed with adjuvant EPOCH-R. DisclosuresNo relevant conflicts of interest to declare.

The utility of multiparametric flow cytometry in the detection of primary effusion lymphoma (PEL).

Primary effusion lymphoma (PEL) is a rare B cell lymphoproliferative disorder that arises predominantly in body cavities causing malignant effusions. The incidence of PEL is very low, accounting for approximately 4% of all HIV-associated non-Hodgkin lymphomas. PEL has also been described in elderly patients and after solid-organ transplantation. It is associated in all cases with human herpes virus 8 (HHV8). We describe a case of PEL in a 88-year-old HIV-negative woman who presented with progressive dyspnea and moderate right-sided pleural effusion without significant lymphadenopathies or other effusions. The cytological study of the pleural fluid revealed a dense proliferation of large plasmablastic cells. A six-color multiparametric flow cytometry immunophenotyping study was carried out, and revealed 45% of large in size and high cellular complexity cells positive for CD45 (dim), CD38, CD138, CD30 and HLA-DR; and negative for CD19, CD20, cytoplasmatic CD79a, surface and cytoplasmic light chains Kappa and Lambda, CD3, CD4, CD5, CD7, CD8, CD28, CD56, CD81, and CD117. In situ hybridization for EBV-encoded smalI RNA was negative and immunohistochemistry for Kaposi sarcoma herpesvirus (HHV8) confirmed the diagnosis of PEL. Our results confirm that flow cytometry bring useful data in the diagnosis of large-cell lymphomas involving body cavities. © 2018 International Clinical Cytometry Society.

Incidence and risk factors for relapses in HIV-associated non-Hodgkin lymphoma as observed in the German HIV-related lymphoma cohort study.

Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate.

Safety and Preliminary Efficacy of Vorinostat With R-EPOCH in High-risk HIV-associated Non-Hodgkin's Lymphoma (AMC-075)

IntroductionVorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV+) or human herpesvirus-8-positive (HHV-8+) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). Patients and MethodsWe performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV+), 1 EBV+/HHV-8+ primary effusion lymphoma, and 1 unclassifiable NHL. VOR was escalated from 300 to 400 mg using a standard 3 + 3 design based on dose-limiting toxicity observed in cycle 1 of R-EPOCH. ResultsThe recommended phase II dose of VOR was 300 mg, with dose-limiting toxicity in 2 of 6 patients at 400 mg (grade 4 thrombocytopenia, grade 4 neutropenia), and 1 of 6 treated at 300 mg (grade 4 sepsis from tooth abscess). Neither VOR, nor cART regimen, significantly altered chemotherapy steady-state concentrations. VOR chemotherapy did not negatively impact CD4+ cell counts or HIV viral loads, which decreased or remained undetectable in most patients during treatment. The response rate in high-risk patients with NHL treated with VOR(R)-EPOCH was 100% (complete 83% and partial 17%) with a 1-year event-free survival of 83% (95% confidence interval, 51.6%-97.9%). ConclusionVOR combined with R-EPOCH was tolerable and seemingly efficacious in patients with aggressive HIV-NHL.

Long-Term Follow up of Patients with HIV-Associated Non-Hodgkin Lymphoma (NHL) after Autologous Stem Cell Transplantation (ASCT)

Background:The Blood and Marrow Transplant Clinical Trials Network 0803 study confirmed the safety and efficacy of ASCT in HIV-infected patients with lymphoma. Short term toxicity and transplant related mortality was low (5.2%) and engraftment, treatment-related mortality and survival outcomes were not statistically significantly different from that of age and diagnosis matched CIBMTR controls. However, median follow up in that trial was 24 months after ASCT, and the questions of second cancer incidence and other infections in a this population remain (Alvarnas et al, ASH 2014). Herein we report the long term outcomes of ASCT in HIV-infected patients.Methods: Retrospective cohort trial of 52 HIV-infected patients who underwent ASCT for high-risk NHL at City of Hope from January 1, 1998 to December 31, 2011. Two patients were excluded from the analysis due to early post-transplant mortality: one patient died at day 22 due to multiorgan failure, and another died at day 72 due to relapsed lymphoma. Fifty patients with a minimum survival of 100-days post ASCT were evaluated for long-term outcomes. Estimation of event-free survival (EFS) and overall survival (OS) was computed using Kaplan-Meier curves and the cumulative incidence of relapse was estimated with competing risk of mortality.Results: Median follow up was 5.43 years (range 0.30-14.96 years). Median age at the time of transplantation was 45 years (range 26-64 years of age). Prior to transplant, 23 patients (46%) were in complete remission and 27 (54%) were in partial remission. Most patients had aggressive NHL, with diffuse large B-cell lymphoma (48%) and Burkitt lymphoma (24%) being most common histologies. Other subtypes included Burkitt-like (10%), plasmablastic (10%), follicular lymphoma (2%), and T-cell lymphomas (6%). Nine patients relapsed (18%), at a median time of 97 days (range 54-253 days) post ASCT. Fifteen patients (30%) died; 8 out of 15 (53%) died due to relapse. Opportunistic infections (OI) occurred in 8 patients (16%) at a median of 0.68 years (range 0.17-10.82 years). Types of OI included CMV retinitis (1), HSV/Zoster (1), HPV (1), Candida esophagitis (1) and PJP (3). One patient died from OI (PJP). Seven patients (14%) developed a second primary malignancy (SPM) at median time to SPM of 5.63 years (range 1.02-14.35 years). Type of SPM included treatment-related myelodysplastic syndrome (t-MDS) with progression to acute myelogenous leukemia (AML) (2) observed at 3.2 years and 12.6 years, respectively, after ASCT; squamous cell carcinoma of the tongue (1), and skin cancers, including melanoma (1) at 14.3 years post ASCT, basal cell carcinoma (2) at 5.5 and 5.6 years post ASCT, and squamous cell carcinoma in situ (1) at 1.0 year post ASCT. Two patients died from the t-MDS.Conclusions: Thirty-five of 50 patients (70%) were alive at the time of analysis confirming the efficacy of this procedure. EFS/OS at 1 year and 5 years post ASCT was 78% (95% CI:67.3%-90.4%)/82% (95% CI: 71.9%-93.4%) and 71.4% (95% CI:59.8%-85.3%)/73.3% (95% CI: 61.8%-86.9%), respectively. Relapse of NHL tended to occur early post-transplant. Cumulative incidence of relapse was 18% at 1 year post ASCT (95% CI: 8.8%-29.8%). Development of OI was also seen early post-ASCT. While SPM appeared as late as 14.35 years following ASCT, it was no higher than that seen in the non-HIV ASCT setting. This is the largest single institution study reporting long-term follow up of HIV-positive patients post ASCT for NHL and demonstrating that while SPM remain a long term concern neither SPM, OI or HIV infection were major factors in mortality. DisclosuresNo relevant conflicts of interest to declare.

A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted R EPOCH Regimen

Background-High grade B-cell NHL's are 200 fold more common in seropositive as compared to seronegative patients. It includes diffuse large B cell lymphoma (DLBCL) (50%), Burkitt's (BL)(40%) and others such as plasmablastic lymphoma(PBL). They are biologically different from their seronegative counterparts with higher incidence of extranodal involvement, advanced stage and poor response to conventional therapy. In addition, they are at a higher risk of chemotherapy side effects and poorly tolerate dose intense regimens. To add to the complexity, social stigma and financial constraints decrease the compliance to therapy. R-EPOCH is designed to provide a balance between efficacy and safety. We report on our cohort of patients who were treated with this protocol.Methods-We retrospectively analysed HIV-associated de-novo high grade B-cell NHL patients who were treated with R EPOCH regimen at Tata Memorial Centre from 2011 till 2015. Patients aged ≥18 years who had received at least 1 cycle were included in the analysis. R EPOCH is an infusional regimen in which the dose of cyclophosphamide is adjusted depending on the baseline CD4+ T cell count and tolerance. The primary objective was the 3-year overall survival(OS), secondary objectives were response rates, the incidence of grade3/4 toxicities, dose intensity and correlation of OS with CD4 count, IPI, duration of HIV, Cyclophosphamide dose intensity (CDI). Demographic features, HIV related details (CD4 count at diagnosis, ART regimen), histological diagnosis, stage, bulky disease, extranodal sites, treatment details (number of cycles, dose administered), response, toxicity and status at last follow up were recorded. Descriptive statistics were summarised with median and range, survival outcomes were analysed with Kaplan meier method and impact of CD 4 count, CDI, IPI and duration of HIV on survival was assessed using log rank test.Results-A total of 40 patients(31males) with a median age-40 years (24-65 years) were treated. B symptoms were present in 19(48%). The cohort comprised of DLBCL-19 (48%), BL-16(40%), High grade B-Cell Lymphoma-Unclassifiable-4 (10%) and PBL 1 (2.5%). 16 (40%) patients had co-morbidities, including co-existent Hepatitis C in 5 and Hepatitis B in 2. HIV infection was detected at the time of lymphoma diagnosis in 18 (45%). The median CD4+ T cell count was 202 cells/mm3, 6 patients (15%)had count of <100/mm3 All patients received HAART while on chemotherapy, NNRTI plus 2 NRTI combination being the commonest regimen-33(82%) patients. Performance status (ECOG) ≤2 was seen in 36(90%) patients. 38 (95%) had stage III/IV disease and bulky disease (defined as size ≥7cm) was seen in 29(72%) patients. Extranodal involvement was seen in 36(90%) patients. Haemoglobin level ≤11g/dL in 10(25%) patients (range- 8.2-15.6 g/dL), serum albumin <4g/dL in 23(58%) patients, serum LDH ≥ upper normal limit -38 (95%)patients. Atleast 4 cycles of chemotherapy were administered to 35 (93%)patients, with 28 (70%) receiving 6 cycles. Cyclophosphamide dose escalation was possible in 18(45%) patients. CNS prophylaxis was administered with intrathecal methotrexate (median number-6) to 36(90%) patients. High dose methotrexate was given to 5 patients. Rituximab was not administered to 5 patients (3 due to CD4 count <100, 2 due to CD20 negativity). Responses were assessed using 18FDG PET-CT scan with complete response-32(80%), partial response-1(3%), disease progression-4(10%) and not evaluable- 4 (7%). Grade ¾ toxicities were seen in 33(83%) patients, with febrile neutropenia-26(65%), mucositis-10(25%) and peripheral neuropathy in5(13%) patients. Out of the 210 cycles administered, there were 41(20%) episodes of hospitalisation (duration ranged from 2-51 days). There were 11(28%) deaths (progression-7, toxicity-2, Not known-2) and 7(18%) patients had progression (4- on treatment progression, 3- relapses). With a median follow-up of 29 months, estimated 3-year OS is 71% (Figure 1) and 3-year progression free survival is 79%. There was no difference in survival based on IPI, CD 4+ T cell count, CDI or duration of HIV.Conclusions-R-EPOCH is a highly effective regimen in seropositive high-grade B-cell lymphoma even in the presence of adverse features (advanced stage, extranodal sites, CNS involvement, low CD4+ T cell count). The emphasis should now be on further reducing the toxicities. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Human immunodeficiency virus-associated lymphomas in the antiretroviral therapy era: Analysis of the National Cancer Data Base.

Antiviral therapy has altered the prognosis of patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL), but patterns of lymphoma-directed therapy in the community are unknown. The authors analyzed the National Cancer Data Base records of 10,769 patients who were diagnosed with HIV-associated lymphoma from 2004 through 2012. Changes in clinical characteristics and chemotherapy delivery over time were evaluated. Factors that were associated with not receiving chemotherapy were studied using multivariable logistic regression, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The proportion of black or Hispanic patients with HIV-associated NHL increased from 41% in 2004 to 55% in 2012 (P < .0001). Chemotherapy was received by 81% of patients with diffuse large B-cell lymphoma, 90% of those with Burkitt lymphoma, 61% of those with primary effusion lymphoma (PEL), and 35% of those with primary central nervous system lymphomas (PCNSL). Between 2004 and 2012, this proportion increased only for patients with PCNSL (P < .00001). Chemotherapy was less likely to be received by patients who were older, black, or without private insurance. It was delivered more frequently in hospitals designated as academic (OR for nonreceipt, 0.68; 95% CI, 0.51-0.92) or in hospitals that had ≥3 HIV-positive cases per year (OR, 0.71; 95% CI, 0.58-0.86). Survival improved in patients with diffuse large B-cell lymphoma (P = .007), Burkitt lymphoma (P = .0002), and PCNSL (P = .019), but not in those with PEL (P = .94). Receipt of chemotherapy in patients with PEL was not associated with better survival. Disparities in chemotherapy delivery need attention, because a majority of HIV-positive patients with NHL in the United States are now black or Hispanic. Higher volume centers were associated with an increased likelihood of chemotherapy administration. Survival gains in patients with PCNSL parallel an increase in chemotherapy use, supporting its role in therapy. [See Editorial on pages 000-000, this issue.] Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2689-2697. © 2016 American Cancer Society.

Tele-Oncology: A Joint Web-Based Clinical Conference Between the Uganda Cancer Institute and the Fred Hutch Cancer Research Center

Abstract 47 Background: The increasing incidence of cancer in sub-Saharan Africa (SSA) has highlighted gaps in access to quality cancer care and subsequent poor outcomes. Two of the factors responsible for this disparity are the limited availability of diagnostic methods and the lack of trained oncologists. Tele-oncology, the application of web-based medical communications, has the potential to bridge the healthcare gap. Here we describe our 3-year experience linking resources between the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, WA and the Uganda Cancer Institute (UCI) Kampala, Uganda, via a monthly conference. Methods: We created a monthly teleconference, each focused on a specific disease group, to provide a clinical treatment and research forum between the UCI and FHCRC. Guided by patients seen at the UCI, clinicians in Uganda present clinical, laboratory, and radiographic data. Case presentations and supporting documents are provided and loaded on a central site. Faculty members from the FHCRC (medical oncology, radiation oncology, surgery, pathology, and radiology, as applicable) are identified in advance and serve as discussants and assist in interpreting data, as well as provide guidance on clinical decision-making. Web conferencing is performed utilizing the Cisco WebEx platform. Results: To date, we have held 36 case conferences and have discussed the following malignancies: Leukemia (including myelodysplasia) (6), gastrointestinal (5), head/neck/lung (5), genitourinary (3), gynecologic (3), lymphoma (2), breast (2), plasma cell dyscrasia (1), soft tissue sarcoma (1), central nervous system (1) and other (5). Two conferences have focused specifically on palliative care. Two locally-relevant treatment guidelines, co-authored by colleagues from Uganda and Seattle, have been published for HIV-associated non-Hodgkin lymphoma and cutaneous T-cell lymphoma as a direct result of these conferences. Conclusions: The monthly teleconference has enhanced education, clinical practice, and collaboration between colleagues in Uganda and Seattle. Future opportunities include the initiation of a core oncology training curriculum, as well as video conferencing capabilities. Similar twinning programs between institutions in resource-rich and resource-limited countries are recommended. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Fred Okuku No relationship to disclose Manoj Menon No relationship to disclose Rachel Kansiime No relationship to disclose Jason Barrett No relationship to disclose Warren Phipps No relationship to disclose Nixon Niyonzima No relationship to disclose Matthew Ulrickson Speakers' Bureau: Incyte Jackson Orem No relationship to disclose Corey Casper Leadership: Temptime Corporation Consulting or Advisory Role: Janssen Pharmaceuticals Research Funding: Janssen Pharmaceuticals Travel, Accommodations, Expenses: Glaxo Smith Kline, Temptime Corporation

Plasmablastic lymphoma of the oral cavity in an undiagnosed HIV-positive patient

Plasmablastic lymphoma is an HIV-associated non-Hodgkin's lymphoma that has a known effect on the oral cavity and jaws. A case is presented of oral plasmablastic lymphoma in an apparently medically well 38 year old male. The patient presented with a large mass fungating from the upper left second molar socket, 2 weeks following extraction. The presence of an exophytic soft tissue lesion in a socket shortly after extraction is an infrequent occurrence. Such lesions should be investigated appropriately as malignant lesions may clinically mimic the appearance of benign lesions.

Auto-Transplant Safe for HIV-Associated Hodgkin and Non-Hodgkin Lymphoma Patients

Auto-Transplant Safe for HIV-Associated Hodgkin and Non-Hodgkin Lymphoma Patients

Prognostic Factors and Outcomes in Primary Effusion Lymphoma in HIV-Infected Patients: A Single Center Experience

Primary effusion lymphoma (PEL) is a human herpesvirus 8-associated non-Hodgkin lymphoma (NHL) that predominantly develops in serous body cavities leading to recurrent lymphomatous effusions. It is poorly understood and very uncommon, accounting for only 3% of all HIV-related NHL. While outcomes have improved in patients with HIV-associated NHL since the widespread use of HAART, the prognosis of PEL remains very poor and median survival is less than 6 months. This study reports our institution’s experience with PEL over the past decade.Between 2004 and 2014, we treated 8 patients with HIV-associated PEL. All patients were male. The median age was 46.5 years old (range 35-63), three were Caucasian, four were Hispanic, and one was African-American. The primary site of involvement was pericardial in 3 patients, pleural in 3 patients, and extra-cavitary in 2 patients. All patients were Ann Arbor stage IV at the time of diagnosis. The mean LDH and CD4 count at time of diagnosis was 625 U/L and 161 cells/mm3, respectively.Of the eight patients identified with PEL, four have achieved complete remission (CR). Prognostic factors associated with achieving CR include compliance with HAART therapy prior to PEL diagnosis as well as lower serum lactate dehydrogenase (LDH) levels (202±30 versus 1049±290, p=.03). Patients achieving CR also had a higher average CD4 count (228±93 versus 95±35, p=.22) at time of diagnosis. Median survival is nearly 6 years for those in CR whereas it was 32 days in patients that died (one from an acute stroke, one from septic shock, and two from progressive disease). All patients who achieved CR had previously diagnosed HIV whereas two of the four who died were previously undiagnosed with HIV. Interestingly, pericardial sites of involvement were associated with significantly better outcomes as compared to pleural sites in our case series, as well. There was no association between outcome and HIV viral load, duration of HIV infection prior to PEL diagnosis, or presence of AIDS-defining illnesses. The patients achieving CR were treated with HAART in addition to Hyper-CVAD (1a-3b) or 6 cycles of CHOP or EPOCH. In addition, two patients received bortezomib as initial therapy. Given its rarity, our knowledge of PEL relies heavily on case reports and small case series. Here we report our institution’s experience with PEL, identify LDH and CD4 as possible prognostic factors in PEL, and suggest bortezomib-based chemotherapy as an effective treatment option in HIV-associated PEL. DisclosuresNo relevant conflicts of interest to declare.

HIV-associated non-Hodgkin lymphoma: viral origins and therapeutic options.

HIV infection is associated with an increased risk of malignancy, especially B-cell lymphoid malignancies. Many of these lymphomas are further driven by concomitant infection with viruses such as Epstein-Barr virus or Human Herpesvirus 8, the latter being implicated in uncommon types of lymphomas seen in the setting of HIV-1 infection. Treatment outcomes have improved due to infusional chemotherapy, high-dose chemotherapy, and effective antiretroviral therapy. Successful functional cure of HIV-1 infection has been demonstrated with the use of allogeneic hematopoietic stem cell transplantation. This result spurred a change in the field of HIV-1 management so that, ultimately, the goals of therapy would shift from not only curing the underlying lymphoma, but also curing the HIV-1 infection. Treatment options will be discussed with an emphasis on hematopoietic cell-based therapy for the underlying HIV infection.

Short Communication: Spectrum of Non-Hodgkin Lymphoma in an Urban Ryan White-Funded Clinic in the Established Antiretroviral Era

People living with HIV/AIDS (PLWHA) are at a higher risk of developing non-Hodgkin lymphoma (NHL). The influence of combined antiretrovirals (cART) on the presentation, treatment, and outcomes of HIV-associated NHL (HIV-NHL) warrants further investigation. We performed a retrospective analysis of PLWHA diagnosed with NHL who received care at the Infectious Diseases Ponce de Leon Center in Atlanta, Georgia, from January 1, 2004 to December 31, 2010. Thirty-five patients with HIV-NHL were identified. Among these patients, 7 had Burkitt lymphoma (BL), 20 had diffuse large B cell lymphoma (DLBCL), 7 had plasmablastic lymphoma (PL), and 1 had primary effusion lymphoma (PEL). The majority of patients (82.9%) presented with advanced disease, and 63% were not on ART at diagnosis. Despite having good performance status at presentation, the majority of patients presented with high International Prognostic Index (IPI) scores. There were differences between the histologic subtypes of NHL in regard to treatment, complications, and outcomes. The median CD4 lymphocyte count at diagnosis was 110 cells/mm(3) for patients with DLBCL [interquartile range (IQR): 66, 203], 165 cells/mm(3) for Burkitt lymphoma (IQR: 36, 199), and 98 cells/mm(3) for plasmablastic lymphoma (IQR: 34, 214). Overall, patients completed 67% of planned chemotherapy cycles. Common causes for chemotherapy termination were persistent myelosuppression (18.2%), social factors (22.7%), and disease progression (36.4%). Social factors included lack of transportation, substance abuse, unstable housing, and poor adherence. Two-year overall survival was 40% for all HIV-NHL. Half of the patients with DLBCL (n=10), 42% of patients with PL (n=3), and only 14.3% of patients with BL (n=1) were alive at 2 years. Among the overall survivors at 2 years, 85.7% had CD4 >200 cells/mm(3) and 78.6% had undetectable HIV viral loads (VL) at that time.