Factors associated with survival in patients with lymphoma and HIV.

OBJECTIVE: To analyze the factors associated with survival in the largest cohort of individuals with HIV and lymphoma so far described in Brazil. DESIGN: A retrospective, observational, multicenter study involving five institutions in São Paulo, Brazil. METHODS: The medical records of consecutive patients with HIV diagnosed with lymphoma between January 2000 and December 2019 were screened. Inclusion criteria consisted of age over 17 years and a biopsy-confirmed diagnosis of lymphoma. The data collected included age, sex, staging (Ann Arbor system), duration of HIV infection, CD4 + lymphocyte count, HIV viral load, lactate dehydrogenase, erythrocyte sedimentation rate and serum beta-2-microglobulin levels, treatment and outcome. RESULTS: Overall, 276 patients were included. Median age was 42 years. Most patients were male (74.3%) and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (28.6% and 46.4%, respectively). Most had non-Hodgkin lymphomas (89.2%, n  = 246), particularly diffuse large B-cell lymphoma (40.9%) and Burkitt lymphoma (26.4%). Hodgkin lymphoma accounted for 9.4%. Advanced stages III/IV were predominant (86.8%). HIV viral load at the moment of lymphoma diagnosis was detectable in 52.9% of patients. A CD4 + cell count of <200 cells/µl was recorded for 53% of the patients. Most patients (62.4%) were on combination antiretroviral therapy. The factors that significantly affected survival were: the ECOG performance status, lymphoma subtype, staging, beta-2-microglobulin level, central nervous system (CNS) infiltration, site of CNS infiltration, relapsed/refractory lymphoma and International Prognostic Index score. CONCLUSIONS: HIV status, CD4 + -lymphocyte count and relapsed/refractory disease affected survival. Rituximab did not appear to improve outcome in HIV-related lymphomas.

Impact of multi-agent systemic therapy on all-cause and disease-specific survival for people living with HIV who are diagnosed with non-Hodgkin lymphoma: population-based analyses from the state of Georgia.

For people living with HIV (PLWH) who are subsequently diagnosed with non-Hodgkin lymphoma (NHL), we investigate the impact of standard-of-care (SoC) cancer treatment on all-cause, NHL-specific, and HIV-specific survival outcomes. The focus is on a registry-derived, population-based sample of HIV + adults diagnosed with NHL within 2004-2012 in the state of Georgia. SoC treatment is defined as receipt of multi-agent systemic therapy (MAST). In multivariable survival analyses, SoC cancer treatment is significantly associated with better all-cause and NHL-specific survival, but not better HIV-specific survival across 2004-2017. Having a CD4 count <200 near the time of cancer diagnosis and Ann Arbor stage III/IV disease are associated with worse all-cause and HIV-specific survival; the effects on NHL survival trend negative but are not significant. Future work should expand the geographic base and cancers examined, deepen the level of clinical detail brought to bear, and incorporate the perspectives and recommendations of patients and providers.

Prognostic variables and 4-year survival outcomes in CD20 Positive AIDS-Related Lymphoma in the Anti-retroviral treatment era: A Retrospective Review from a Single Centre in KwaZulu-Natal, South Africa.

OBJECTIVE: To describe 4-year survival outcomes and assess the value of established and additional relevant variables to predict complete response (CR), four-year progression-free survival (PFS) and overall survival (OS) of CD20 positive AIDS-Related Lymphoma (ARL) treated with standard combination chemotherapy. METHOD: We performed a retrospective review of patients diagnosed with CD20 positive ARL between 2006 and 2016. All patients over 12 years of age who received at least one cycle of combination chemotherapy with curative intent were included in the analysis. Variables assessed included the International Prognostic Index (IPI), age-adjusted-IPI, age, gender, B symptoms, extent of disease, functional performance status, CD4 cell count, viral load, concurrent ART with chemotherapy, rituximab inclusion, and number of chemotherapy cycles used. Kaplan-Meier survival curves for OS and PFS at 4 years were compared for IPI and aaIPI using the log-rank test. A Cox proportional hazards model was used to investigate the effects of prognostic variables for patients achieving OS and PFS at 4 years and logistic regression for patients achieving CR. RESULTS: A total of 102 patients were included in the analysis. At year four of follow-up, the OS was 50% (n = 51) and PFS was 43% (n = 44). Attaining a CR and male gender were significantly associated with improved 4-year OS (p<0.001 and p = 0.028 respectively) and PFS (p<0.001 and 0.048 respectively). A viral load of < 50 copies/ml was associated with a higher complete response rate (aOR 6.10 [95% CI 1.15, 24.04], p = 0.01). Six or more cycles of chemotherapy was superior to fewer cycles for both PFS (aHR 0.17 [95% CI 0.10, 0.29]) and OS (aHR 0.12 [95% CI 0.07, 0.22]) with p-value < 0.001 for both PFS and OS. The Kaplan-Meier survival estimates demonstrated the prognostic utility of the IPI and aaIP for OS (p = 0.002 and 0.030 respectively) and the IPI for PFS (p = 0.002). CONCLUSION: This study is a first from a high prevalence HIV area in KwaZulu-Natal, South Africa, and confirms the utility of the internationally accepted prognostic scoring systems in predicting survival in CD20 positive ARL in the local population.

HIV-related lymphomas.

PURPOSE OF REVIEW: To summarize the recent evidence on the pathology, current standard of care and recent advances in the treatment of HIV-related lymphomas. RECENT FINDINGS: Lymphomas remain a major cause of morbidity and mortality in people living with HIV, even in the era of combination antiretroviral therapy (cART). However, treatment outcomes for these malignancies have improved in recent decades, due to full-dose chemotherapy, effective cART and supportive care. Recent advances include the identification of novel driving signaling pathways as promising molecular targets to improve lymphoma outcomes. SUMMARY: Patients with HIV-related lymphomas who receive effective cART should be treated like the general population.

A Novel Prognostic Score Including the CD4/CD8 for AIDS-Related Lymphoma.

Background: A simple and clinically applicable prognostic scoring system for AIDS-related lymphoma (ARL) in the era of combination antiretroviral therapy (cART) is needed to better stratify patients' risks and to assist in the decision-making of therapeutic strategies. Methods: We conducted a retrospective multicenter cohort study in 138 primary ARL patients over an 8-year period from 2013 to 2020. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were performed to identify the association between patient-, lymphoma-, and HIV-specific variables with progression-free survival (PFS) and overall survival (OS). The incremental prognostic value of novel inflammatory biomarkers in the International Prognostic Index (IPI) was evaluated by comparing the receiver operating characteristic (ROC) curves, the concordance index (C-index), and the integrated Brier score (IBS). Results: The median age was 49.14 ± 14.20 (range 18-79) years, 81.9% were men, and the median follow-up was 44.94 (95% CI = 37.05-52.84) months. The 3-year OS and PFS were 39.4% (95% CI = 16.3-21.2) and 38.7% (95% CI = 14.5-19.7), respectively. We found that age, extranodal sites, bulky mass, CD4 T-cell counts, CD4/CD8 ratio, and hypoalbuminemia were associated with OS (all P < 0.05) at both univariate and multivariate analyses. Of the new inflammatory markers, only the CD4/CD8 ratio was an independent prognostic parameter of OS and PFS. A lower CD4/CD8 ratio was strongly associated with adverse clinical factors, including older age, advanced Ann Arbor stage, more extranodal sites, elevated erythrocyte sedimentation rate, prior history of HIV, higher red cell distribution width ratio, hypoproteinemia, and emaciation. When the CD4/CD8 ratio was added to the IPI, the composite HIV-IPI score showed significantly better discrimination than IPI alone [AUC (95% CI): HIV-IPI, 0.83 (0.77-0.89) vs. IPI, 0.72 (0.70-0.85)]. The HIV-IPI model provided good predictive performance [C-index (95% CI): HIV-IPI, 0.82 (0.81-0.83) vs. IPI, 0.75 (0.73-0.77), P < 0.001] and a satisfactory calibration function. Conclusions: The CD4/CD8 ratio, an inexpensive and readily available marker, is a powerful independent prognostic parameter in patients with ARL. Furthermore, when the CD4/CD8 ratio is used in combination with IPI, it increases prognostic ability. The useful prediction of expected outcomes in ARL can inform treatment decisions.

Long-term remission of AIDS-related primary central nervous system lymphoma in a patient under antiretroviral therapy: a case report and review of the literature.

BACKGROUND: AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/µl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2-3 months if left untreated. CASE DESCRIPTION: A 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT. CONCLUSION: Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.

Lymphoma in HIV-2-infected patients in combination antiretroviral therapy era.

OBJECTIVE: To describe lymphoma in HIV-2-infected patients and compare their characteristics with lymphoma in HIV-1-infected patients. DESIGN: Ancillary analysis from a single center prospective cohort of HIV-lymphoma. METHODS: We report on 16 patients with HIV-2-lymphoma diagnosed after 1996 and included in a prospective cohort of HIV lymphoma. Five additional HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I (6 lymphomas) are separately reported. The incidence of lymphoma in HIV-2-infected patients was evaluated in the French multicentric HIV-2 cohort. RESULTS: Incidence of lymphoma in the French HIV-2 cohort was estimated as 0.6/1000 patient-years. In our series, the median CD4+ cell count was 166 × 106/l at the time of lymphoma diagnosis and 50% of patients had undetectable plasma HIV-2-RNA. Lymphomas were non-Hodgkin lymphoma (n = 12) and classical Hodgkin lymphoma (n = 4). Similarly to HIV-1-lymphoma, clinical presentation was aggressive in most cases. All but one patient received intensive chemotherapy. Complete remission was achieved in 13 cases and 1 patient relapsed. The overall survival was not statistically different from that observed in patients with HIV-1 lymphoma. The six additional lymphomas observed in five HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I presented with similar clinical presentation but worse prognosis. CONCLUSION: Despite the lower pathogenicity of HIV-2, the risk of developing lymphoma seems to be close to that observed in HIV-1 population with similar lymphoma characteristics. Compared with HIV-1, HIV-2-infected patients developed lymphoma later in their life but at a similar CD4+ cell count level.

[Human immunodeficiency virus and lymphoma]. / Virus de l'immunodéficience humaine et lymphome.

Lymphomas remain a leading cause of morbidity and mortality for HIV-positive patients. The most common lymphomas include diffuse large B-cell lymphoma, Burkitt lymphoma, primary effusion lymphoma, plasmablastic lymphoma and Hodgkin lymphoma. Appropriate approach is determined by lymphoma stage, performans status, comorbidities, histological subtype, status of the HIV disease and immunosuppression. Treatment outcomes have improved due to chemotherapy modalities and effective antiretroviral therapy. This review summarizes epidemiology, pathogenesis, pathology, and current treatment landscape in HIV associated lymphoma.

Immune Activation and Microbial Translocation as Prognostic Biomarkers for AIDS-Related Non-Hodgkin Lymphoma in the AMC-034 Study.

PURPOSE: AIDS-related non-Hodgkin lymphoma (ARL) is the most common cancer in HIV-infected individuals in the United States and other countries in which HIV-positive persons have access to effective combination antiretroviral therapy (cART). Our prior work showed that pretreatment/postdiagnosis plasma levels of some cytokines, such as IL6, IL10, and CXCL13, have the potential to serve as indicators of clinical response to treatment and survival in ARL. The aims of this study were to identify novel prognostic biomarkers for response to treatment and/or survival in persons with ARL, including biomarkers of microbial translocation and inflammation. EXPERIMENTAL DESIGN: We quantified plasma levels of several biomarkers (sCD14, LBP, FABP2, EndoCab IgM, IL18, CCL2/MCP-1, sCD163, IP-10/CXCL10, TARC/CCL17, TNFα, BAFF/BLyS, sTNFRII, sCD44, and sIL2Rα/sCD25) by multiplexed immunometric assays (Luminex) or ELISA in plasma specimens obtained from ARL patients enrolled in the AMC-034 trial, which compared infusional combination chemotherapy (EPOCH: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with concurrent or sequential rituximab. Plasma was collected prior to the initiation of therapy (n = 57) and after treatment initiation (n = 55). RESULTS: We found that several biomarkers decreased significantly after treatment, including TNFα, sCD25, LBP, and TARC (CCL17). Moreover, pretreatment plasma levels of BAFF, sCD14, sTNFRII, and CCL2/MCP-1 were univariately associated with overall survival, and pretreatment levels of BAFF, sTNFRII, and CCL2/MCP-1 were also associated with progression-free survival. CONCLUSIONS: Our results suggest that patients with ARL who responded to therapy had lower pretreatment levels of inflammation and microbial translocation as compared with those who did not respond optimally.

Incidence and spectrum of infections among HIV/AIDS patients with lymphoma during chemotherapy.

Introduction Lymphoma is the most common cancer in HIV/AIDS patients. Chemotherapy regiments recommended for lymphomas in HIV-negative patients are also used for lymphomas in HIV/AIDS patients. Little is known about the infections among HIV/AIDS patients with lymphoma undergoing chemotherapy. Methods This retrospective study investigated the incidence, spectrum of and risk factors for infections during chemotherapy in 164 HIV/AIDS patients with lymphoma admitted to Shanghai Public Health Clinical Center from July 2013 to December 2020. Results The median age of the patients was 43 years old; 90.9% (149/164) were male. A total of 112 (68.3%) patients had a CD4 count < 200 cells/µL at lymphoma diagnosis. Diffuse large B-cell lymphoma (56%, 91/164) and Burkitt lymphoma (28%, 46/164) were the two most common subtypes of lymphoma. Among the 137 patients who underwent chemotherapy (total cycles = 749), 58.4% (80/137) of patients experienced a total of 153 episodes of infection, with an incidence rate of 20.4% (153/749). The most commonly seen infections were lung infection (29.2%, 40/137) and febrile neutropenia (27.0%, 37/137). Multivariate analysis showed that grade 4 neutropenia during chemotherapy (OR = 7.128, 95% CI 3.051-16.654, p < 0.001) and duration of antiretroviral treatment at lymphoma diagnosis <6 months (OR = 3.520, 95% CI 1.432-8.653, p = 0.006) were independent risk factors for infection during chemotherapy. Conclusions A large proportion of HIV/AIDS patients with lymphoma may be at risk of infection during chemotherapy. Effective measures should be taken for patients with high risk factors to prevent the occurrence of infection.

Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin's lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control. METHODS: We conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute. RESULTS: We identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1-21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2-3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide. CONCLUSIONS: Treatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma.

Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.

Primary Vitreoretinal Lymphoma in HIV Infection.

Purpose: To describe the epidemiology, clinical characteristics, diagnosis and treatment of human immunodeficiency virus (HIV)-related primary vitreoretinal lymphoma (PVRL).Methods: Narrative literature review.Results: HIV-related PVRL occurs in persons who are relatively young and generally have very low CD4+ T-cell counts. Vitritis with subretinal or sub-retinal pigment epithelial infiltrates is typical. Vitreous cytology remains the gold standard for diagnosis, supplemented by flow cytometry and genetic analyses of tumor cells, and measurement of aqueous or vitreous interleukin-10 levels. Concurrent brain involvement also may establish the diagnosis. Treatment includes antiretroviral therapy (ART), systemic chemotherapy (usually methotrexate-based) and local ocular treatment (intravitreal methotrexate, intravitreal rituximab, external beam radiotherapy). Systemic chemotherapy is of uncertain value for PVRL without other central nervous system involvement. Prognosis is poor, but has improved significantly compared to the pre-ART era.Conclusions: Ophthalmologists should consider the diagnosis of PVRL in HIV-positive individuals who present with intermediate or posterior uveitis.

Survival of HIV-infected patients with high-grade non-Hodgkin's lymphomas: A retrospective study of experiences in Zimbabwe.

BACKGROUND: Rituximab in combination with chemotherapy is now widely accepted as standard of care for AIDS-related lymphomas (ARLs) of B-cell origin. However, the clinical impact of rituximab in resource limited settings remains unknown. Different settings and patient heterogeneity may affect the effect of any given treatment. The study objectives were to determine if rituximab use was associated with improved 18-month overall survival (OS) of patients with ARLs and to identify correlates of 18-month OS. METHODS: A retrospective review of medical records of adult HIV infected patients treated for high-grade large cell non-Hodgkin's lymphoma with chemotherapy +/- rituximab between 2015-2017 was conducted. Vital status and disease progression/relapse at 18 months were determined. Survival functions were estimated using Kaplan-Meier methodology. Equality of survival functions were assessed using Log-rank tests and Cox regression analysis to identify risk factors for mortality. RESULTS: One hundred and twenty-four eligible medical records were identified. This was a cohort of black Africans with a median age of 42 (IQR: 33-47) and a 57% male gender distribution. Overall survival at 6, 12 and 18 months for the population was 75.9%, 44.0% and 30.6% respectively. Over the study period, 72.6% of patients were diagnosed with disease progression/ relapse. There was a higher rate of rituximab use in patients who were treated at a private institution and those with medical insurance. Rituximab use was not associated with a reduction in 18-month mortality [adjusted hazard ratio (aHR)1.28, (95% CI 0.63-2.60)]. Risk factors for 18-month mortality were male gender [aHR 1.89, (95% CI 1.04-3.43)], age 40+ years [aHR 2.49, (1.33-4.67)], receipt of <3 chemotherapy cycles [aHR 2.48, (95% CI 1.33-4.60)] and low socioeconomic status [aHR 2.44, (95% CI 1.28-4.67)]. CONCLUSIONS: Predictors of mortality were male gender, older age, low socioeconomic status and receipt of a less than half of the recommended number of chemotherapy cycles. Rituximab use was not associated with an improvement in 18-month OS in Zimbabwean patients with ARLs.

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

EPOCH (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.

HIV-Related Lymphoproliferative Diseases in the Era of Combination Antiretroviral Therapy.

HIV-positive patients have a 60- to 200-fold increased incidence of Non-Hodgkin Lymphomas (NHL) because of their impaired cellular immunity. Some NHL are considered Acquired Immunodeficiency Syndrome (AIDS) defining conditions. Diffuse large B-cell Lymphoma (DLBC) and Burkitt Lymphoma (BL) are the most commonly observed, whereas Primary Effusion Lymphoma (PEL), Central Nervous System Lymphomas (PCNSL), Plasmablastic Lymphoma (PBL) and classic Hodgkin Lymphoma (HL) are far less frequent. Multicentric Castleman disease (MCD) is an aggressive lymphoproliferative disorder highly prevalent in HIV-positive patients and strongly associated with HHV-8 virus infection. In the pre-Combination Antiretroviral Therapy (CART) era, patients with HIV-associated lymphoma had poor outcomes with median survival of 5 to 6 months. By improving the immunological status, CART extended the therapeutic options for HIV positive patients with lymphomas, allowing them to tolerate standard chemotherapies regimen with similar outcomes to those of the general population. The combination of CART and chemotherapy/ immuno-chemotherapy treatment has resulted in a remarkable prolongation of survival among HIVinfected patients with lymphomas. In this short communication, we briefly review the problems linked with the treatment of lymphoproliferative diseases in HIV patients. Combination Antiretroviral Therapy (CART) not only reduces HIV replication and restores the immunological status improving immune function of the HIV-related lymphomas patients but allows patients to deal with standard doses of chemotherapies. The association of CART and chemotherapy allowed to obtain better results in terms of overall survival and complete responses. In the setting of HIVassociated lymphomas, many issues remain open and their treatment is complicated by the patient's immunocompromised status and the need to treat HIV concurrently.

Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice.

The MATRix chemoimmunotherapy regimen is highly effective in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). However, nothing is known about its feasibility and efficacy in everyday practice, where patients are more often older/frailer than those enrolled in clinical trials. We conducted a retrospective study addressing tolerability/efficacy of MATRix in 156 consecutive patients with newly diagnosed PCNSL treated outside a clinical trial. Median age and ECOG Performance Status of considered patients were 62 years (range 28-78) and 2 (range 0-4). The overall response rate after MATRix was 79%. Nine (6%) treatment-related deaths were recorded. After a median follow-up of 27.4 months (95% confidence interval [CI] 24.4-31.9%), the two-year progression-free and overall survival were 56% (95% CI 48.4-64.9%) and 64.1% (95% CI 56.7-72.5%) respectively. Patients not eligible for the IELSG32 trial were treated with lower dose intensity and had substantially worse outcomes than those fulfilling inclusion criteria. This is the largest series of PCNSL patients treated with MATRix outside a trial and recapitulates the IELSG32 trial outcomes in the non-trial setting for patients who fit the trial criteria. These data underscore the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.

DUSP22-IRF4 rearrangement in AIDS-associated ALK-negative anaplastic large cell lymphoma.

Patients with AIDS have increased risk of developing lymphomas, such as anaplastic large cell lymphoma (ALCL), which generally carry a poor prognosis. The DUSP-IRF4 genetic rearrangement in ALCL confers a favourable prognosis in HIV-negative patients; it is unknown how this interacts clinically with HIV/AIDS. A man aged 53 years presented with subcutaneous nodules on the scalp and axillae, and diffuse lymphadenopathy. Biopsy of subcutaneous nodule and lymph node showed large atypical anaplastic lymphocytes which were CD30+ and anaplastic lymphoma kinase-negative, consistent with primary systemic ALCL. In addition, he was found to be HIV-positive and diagnosed with AIDS. Genetic testing of the tissue revealed a DUSP22-IRF4 rearrangement. Complete remission was achieved with HyperCVAD and subsequent brentuximab vedotin monotherapy. We report a case of AIDS-associated primary systemic ALCL with a DUSP22-IRF4 rearrangement. AIDS-associated ALCL is an aggressive lymphoma, with a poor prognosis. However, the presence of the genetic rearrangement, previously unseen in this disease, drastically altered the disease course. This case highlights the value of genetic testing and identifies DUSP22-IRF4-associated ALCL in the setting of HIV-associated lymphoproliferative disorders.