AIDS-related Lymphoma Research Articles

Clinical features and prognostic factors of AIDS-associated diffuse large B-cell lymphoma

To explore the general clinical features and treatment outcomes of patients with AIDS-related diffuse large B-cell lymphoma (AIDS-DLBCL) and provide a theoretical basis for diagnosis and treatment, survival prognosis, prevention and management of AIDS-DLBCL patients. AIDS-DLBCL patients who received combined antiretroviral therapy (cART) at Changsha First Hospital from January 2017 to January 2020 were selected in this study. The survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to analyze the association between AIDS-DLBCL specific variables and progression-free survival and overall survival. Correlation analysis was conducted based on the clinical features of the patients. A total of 50 AIDS-DLBCL patients were included. Their median age (Q1, Q3) was 52 (44, 59) years, of whom 46 (92%) were male. About 20 (40%) patients received treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), while 23 patients (46%) received treatment with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Survival curve analysis showed that the 2-year progression-free survival rate and overall survival rate of AIDS-DLBCL patients were 56.9% and 61.6%, respectively. Patients with RCHOP protocol combined with EBV-DNA≥1 000 copies/ml had higher progression-free survival rate (χ2=3.844, P=0.043) and overall survival rate (χ2=4.662, P=0.031) than those with CHOP protocol combined with EBV-DNA≥1 000 copies/ml. A multivariate analysis showed that male (HR=2.70, 95%CI:1.10-6.80), EB viral load≥1 000 copies/ml (HR=1.75, 95%CI:1.12-2.84), HIV-RNA≥200 copies/ml (HR=4.64, 95%CI: 1.73-12.15), ECOG PS score of 2 to 4 points (HR=3.54, 95%CI:1.62-7.33), and international prognostic index (IPI) score of 3 to 5 points (HR=5.21, 95%CI:1.39-20.14) were at a higher risk of disease progression. Patients with EB viral load≥1 000 copies/ml (HR=0.07, 95%CI:0.05-0.93) on the RCHOP regimen had a small risk of disease progression. Males (HR=2.87, 95%CI:1.65-9.17), EB viral load≥1 000 copies/ml (HR=1.61, 95%CI:4.02-9.36), HIV-RNA≥200 copies/ml (HR=1.19, 95%CI:1.58-2.74), ECOG PS score of 2 to 4 (HR=6.42, 95%CI:2.55-14.33), IPI score of 3 to 5 points (HR=2.78, 95%CI:1.41-12.96) had a high risk of mortality. Patients with EB viral load≥1 000 copies/ml (HR=0.24, 95%CI:0.64-0.90) on the RCHOP regimen had a low risk of mortality. In summary, males, ECOG physical status score of 2 to 4 points, IPI score of 3 to 5 points, EB viral load≥1 000 copies/ml and HIV viral load≥200 copies/ml are risk factors affecting progression-free survival and overall survival of AIDS-DLBCL patients. RCHOP regimen combined with EB viral load≥1 000 copies/ml is a protective factor affecting progression-free survival and overall survival in AIDS-DLBCL patients.

High-grade B-cell lymphoma with 11q aberration in the HIV setting: a clinicopathological study of 10 cases and literature review

High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P < 0.001), background rich in eosinophils (P = 0.002), higher expression of the germinal centre marker LMO2 (P = 0.080), lower expression of MUM1 (P = 0.004), BCL2 (P = 0.007), and LEF1 (P = 0.080), and lower positivity for EBER in situ hybridisation (P = 0.027). Notably, one case in our series was EBV-positive, a finding not previously reported in the literature. Furthermore, comparing the prognosis between these two groups, AR-HGBL-11q showed a relatively favorable prognosis (P = 0.15), although the difference was not statistically significant. We analyzed this rare lymphoma entity in the HIV setting and highlighted the importance of integrating histomorphological and immunophenotypic features in its diagnosis and classification.

Promising immunotherapeutic approaches for primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a large B-cell neoplasm usually presenting as a serious effusion in body cavities without detectable tumor masses. It is an AIDS-related non-Hodgkin's lymphoma (HL) with human herpes virus 8 (HHV8)/Kaposi sarcoma-associated herpes virus (KSHV) infection. A combination antiretroviral therapy (cART) prolongs the lifespan of AIDS and AIDS-related malignant lymphoma patients, but PEL continues to have a dismal prognosis. PEL showed disappointing outcomes with standard chemotherapy such as CHOP or CHOP-like regimens. A PEL status highlights the urgent need for new therapeutic approaches and treatment strategies and improve clinical outcomes. This review discusses the current knowledge and some recent clinical trials for PEL in the platform of immunotherapy as well as promising future immunotherapeutic approaches for PEL.

Expression and prognostic significance of the PD-1/PD-L1 pathway in AIDS-related non-Hodgkin lymphoma.

Immune tolerance and evasion play a critical role in virus-driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, in aggressive acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) remain poorly understood, particularly in the Epstein-Barr virus (EBV)-positive subset. We used insitu hybridization with EBV-encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD-1/PD-L1/L2 pathway in a multi-institutional cohort of 58 patients with AR-NHL and compared EBV-positive and EBV-negative cases. The prevalence of EBV+ in AR-NHL was 56.9% and was associated with a marked increase in the expression of PD-1/PD-L1/PD-L2 in malignant cells. Patients with AR-NHLs who tested positive for both EBER and PD-1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD-L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD-1 tissue-expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD-1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD-L1 (r = 0.354, p = 0.014) expression. These data emphasize the importance of PD-1-mediated immune evasion in the complex landscape of immune oncology in AR-NHL co-infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Safety and Efficacy of Autologous HSCT in Nine Patients with AIDS-Related Non-Hodgkin Lymphoma

Background：In recent years, with the application of HIV combined with resistance retroviral therapy, the number of AIDS-NHL patients has gradually increased, surpassing Kaposi's sarcoma and becoming the first AIDS-related tumor. The prognosis of AIDS-NHL patients is worse than that of ordinary NHL patients, and more powerful treatment is needed. To analyze the safety and efficacy of 9 AIDS-related non-Hodgkin lymphoma (AIDS-related non-Hodgkin lymphoma, AIDS-NHL) treated with autologous hematopoietic stem cell transplantation (auto-hematopoietic stem cell transplantation, ASCT). Methods: 9 patients with AIDS-NHL were prospectively treated for their safety and efficacy. Results: The male to female ratio of 9 AIDS-NHL patients was 8:1, and the median age was 38 years. The pathology types were 4 DLBCL, 2 PBL, 1 BL, 1 HGBL and 1 HL, including 3 patients with refractory relapse (1 each of DLBCL, HGBL and PBL). Except for three patients with refractory relapse, the remaining six patients underwent first-line autologous HSCT. One PBL stage was in stage I low-risk group and the remaining patients were in stage III - IV high-risk group. Before transplantation, one patient was progressive, one patient was in partial remission, and the other patients achieved complete remission after chemotherapy. All patients underwent autologous HSC mobilization using PEG-G-CSF, with all CD34 + cell numbers&amp;gt; 210 ^ 6 / Kg. Transplantation pretreatment was performed with the BeEAM protocol, with a median time to granulocyte engraftment of 11 days and a median time to platelet engraftment of 14 days, with no transplant-related death. Two patients who did not achieve CR before transplantation all died due to disease progression within 3 months after transplantation, and the remaining patients remained in complete disease remission through follow-up until February 28,2023. Conclusion: AIDS-NHL patients are aggressive and have a poor prognosis, and active treatment is needed to improve their long-term survival. Our center prospectively performed autologous HSCT in nine patients with AIDS-NHL, and the results showed that the time of granulocyte and platelet engraftment was consistent with that of ordinary NHL patients, with no transplant-related death and was well tolerated. Failure to achieve complete remission before transplantation may be one of the adverse factors for the early death of patients.

A Prognostic Nomogram Survival Model for Newly Diagnosed Patients with AIDS-Related Diffuse Large B-Cell Lymphoma: A Multicenter Cohort Study in China

BACKGROUND The prognosis of patients with AIDS-related diffuse large B-cell lymphoma(AR-DLBCL) becomes very poor when the lymphoma relapses or is refractory to first line immunochemotherapy. We aimed to develop a novel ARDPI nomogram prognostic model for risk stratification so as to guide individualized treatment to achieve sustained remission and improve the overall prognosis for newly-diagnosed AR-DLBCL patients. METHODS We interrogated data from 306 patients with newly-diagnosed AR-DLBCL. We filtered variables using LASSO regression and Cox regression to identify prognostic co-variates and develop a survival model, we termed AR-DLBCL Prognostic Index (ARDPI). We evaluated model discrimination, calibration and clinical benefit by Area Under the Receiver-Operator Characteristic (AUROC), calibration plots and decision curve analysis (DCA). Next, we compared the ARDPI model discrimination, calibration and clinical benefit with the IPI and NCCN-IPI models using the same methods. Lastly, we stratified patients into three survival risk cohorts based on ARDPI model by X-tile selecting cutoff point. RESULTS 7 co-variates were independently correlated with survival and were used to develop the ARDPI model including age, lymphocyte monocyte ratio (LMR), CD5 expression on lymphoma cells, blood EBV-DNA copy number, CD4/CD8 ratio, central nervous system (CNS) involvement and anti-HIV therapy (ART). AUROCs of ARDPI model for 1-, 3-, and 5-year were 0.80 (95% Confidence Interval [CI], 0.72, 0.88), 0.78 (0.69, 0.87) and 0.77 (0.63, 0.91). Predicted and calibrated values were concordant. The DCA curve had higher net benefit using the ARDPI model. Prediction accuracy of the ARDPI model was better compared with the IPI and NCCN-IPI models. For example, 3-year survival AUROC in the ARDPI model was 0.78 (0.69, 0.87) compared with the IPI (0.53 [0.43, 0.63] P&amp;lt; 0.001) and the NCCN-IPI (0.52 [0.42, 0.62] P&amp;lt; 0.001). Using the ARDPI model, we identified 3 survival risk cohorts with 3-year survivals of 0.80 , 0.38 and 0.09 ( P&amp;lt;0.001). CONCLUSION The ARDPI has good survival prediction accuracy in newly-diagnosed persons with AIDS-related DLBCL and using it has clinical benefit.Accuracy is better than the IPI and NCCN-IPI models. Validation of our conclusions is needed.

High Frequency Mutant Genes and Prognosis Value of HIV-Related Diffuse Large B-Cell Lymphoma

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype in AIDS-related lymphoma (ARL) in HIV-infected patients, and the probability of DLBCL in HIV-infected patients is up to 17 times higher than that of the healthy population. However, the genetic mutation profile of HIV-associated DLBCL is still controversial, and the gene regulatory mechanism of HIV infection leading to the high incidence of DLBCL is still unclear. Methods: A total of 12 HIV-positiveDLBCL and 39 HIV-negativeDLBCL patients who treated in Chongqing University Cancer Hospital from March 2022 to October 2022 were enrolled. Tumor tissue samples were selected to detect by second-generation sequencing technology, and gene heat mapping was used to analyze the high-frequency mutant genes in HIV-positive lymphoma patients, comparing the differences mutant genes between HIV-positive and HIV-negative DLBCL patients. The specific mutant genes in HIV-positive DLBCL were screened, and Kaplan-Meier estimate the impact of specific gene changes on disease prognosis in analyze DLBCL lymphoma. Results Compared with HIV-negative DLBCL patients, 12 patients with HIV-positive DLBCL were mostly male (91.7%), and the disease subtype was mostly germinal center B-cell like(GCB) subtype (75%). HIV-positive DLBCL patients were associated with EBV infection, elevated LDH, increased proportion of CD4 + cells &amp;lt; 200 (cell/ul), and more aggressive. The gene heat mapping results showed that TP53, TBL1XR1 and KMT2D had higher mutations in HIV-positive DLBCL and HIV-negative DLBCL patients. Compared with HIV-positive DLBCL, HIV-negative DLBCL patients were more likely to have gene mutations such as IGLL5, KMT2C, CD79B, BTG1, HIST1H1E, TNFRSF14, B2M. Compared with HIV-negative DLBCL patients, HIV-positive DLBCL patients detected more complex gene mutation sites, and were more common to have gene mutations including TP53, LRP1B, MYC, NOTCH2, SPEN, EP300, SOCS1, TYK2, ARID1A, GNA13, MAP2K1. Among those gene mutations, LRP1B, MYC, TYK2 have a higher probability in HIV-positive DLBCL patients (P&amp;lt;0.05). Compared with HIV-negative DLBCL patients, HIV-positive DLBCL patients have a worse prognosis by Kaplan-Meier analysis, and patients with LRP1B, MYC, TYK2 mutations had a longer time to achieve complete remission. Conclusion HIV-positive DLBCL patients are more prone to gene mutations, and the mutant genes are more complex and diverse. LRP1B, MYC and TYK2 gene mutations may play an important role in the occurrence and development of HIV-positive DLBCL and affect the prognosis of patients. Keyword HIV; lymphoma; genetic mutation; prognosis

Efficacy of Antibodies Targeting TfR1 in Xenograft Mouse Models of AIDS-Related Non-Hodgkin Lymphoma.

Transferrin receptor 1 (TfR1), also known as CD71, is a transmembrane protein involved in the cellular uptake of iron and the regulation of cell growth. This receptor is expressed at low levels on a variety of normal cells, but is upregulated on cells with a high rate of proliferation, including malignant cells and activated immune cells. Infection with the human immunodeficiency virus (HIV) leads to the chronic activation of B cells, resulting in high expression of TfR1, B-cell dysfunction, and ultimately the development of acquired immunodeficiency syndrome-related B-cell non-Hodgkin lymphoma (AIDS-NHL). Importantly, TfR1 expression is correlated with the stage and prognosis of NHL. Thus, it is a meaningful target for antibody-based NHL therapy. We previously developed a mouse/human chimeric IgG3 specific for TfR1 (ch128.1/IgG3) and showed that this antibody exhibits antitumor activity in an in vivo model of AIDS-NHL using NOD-SCID mice challenged intraperitoneally with 2F7 human Burkitt lymphoma (BL) cells that harbor the Epstein-Barr virus (EBV). We have also developed an IgG1 version of ch128.1 that shows significant antitumor activity in SCID-Beige mouse models of disseminated multiple myeloma, another B-cell malignancy. Here, we aim to explore the utility of ch128.1/IgG1 and its humanized version (hu128.1) in mouse models of AIDS-NHL. To accomplish this goal, we used the 2F7 cell line variant 2F7-BR44, which is more aggressive than the parental cell line and forms metastases in the brain of mice after systemic (intravenous) administration. We also used the human BL cell line JB, which in contrast to 2F7, is EBV-negative, allowing us to study both EBV-infected and non-infected NHL tumors. Treatment with ch128.1/IgG1 or hu128.1 of SCID-Beige mice challenged locally (subcutaneously) with 2F7-BR44 or JB cells results in significant antitumor activity against different stages of disease. Treatment of mice challenged systemically (intravenously) with either 2F7-BR44 or JB cells also showed significant antitumor activity, including long-term survival. Taken together, our results suggest that targeting TfR1 with antibodies, such as ch128.1/IgG1 or hu128.1, has potential as an effective therapy for AIDS-NHL.

NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

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.

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. 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. 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). 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.

High expression of HIV-1 matrix protein p17 in both lymphoma and lymph node tissues of AIDS patients

BackgroundHIV-1 matrix protein p17 was found to be associated with lymphoma development in vitro. This study aimed to elucidate the pathogenetic roles of HIV-1 p17 in AIDS-related lymphoma. MethodsExpression of HIV-1 proteins p17, p24, nef and tat were evaluated in tumor tissue samples from 60 lymphoma patients and lymph node samples from 23 non-lymphoma patients with HIV-1 infection by immunohistochemistry. Microvascular density (MVD) determined by CD34 were also assessed in tumor tissues. Clinicopathological data of AIDS patients with lymphoma were collected retrospectively. ResultsThe subtypes of lymphoma among sixty AIDS patients were diffuse large B-cell lymphoma (32 cases), Burkitt lymphoma (23 cases), Hodgkin’s lymphoma (4 cases), and plasmablastic lymphoma (1 case). The expression rate of HIV-1 p17 in lymphoma and non-lymphoma group was 63 % (38/60) and 61 % (14/29) respectively, with no significant difference (p = 0.835). The positive expression rate of p17 in both groups was significantly higher than that of p24, nef and tat (p < 0.05). The expression of p17 was associated with a higher MVD in the lymphoma group (p < 0.05). There were no significant differences in the 2-years overall survival between p17 positive and negative group (61 % vs. 50 %, p = 0.525). ConclusionThe common expression of HIV-1 matrix protein p17 in both lymphoma and lymph node tissues of AIDS patients and the association between p17 expression and the higher MVD suggest that the accumulation and persistence of p17 in tissues may play a role in lymphoma development.

Kaposi sarcoma (KS) with primary effusion lymphoma in HIV infected MSM (men having sex with men) co-infected with pulmonary tuberculosis and syphilis: a case report from India

We describe a case of a 30-year-old MSM recently diagnosed with HIV, immunocompromised with a purplish or brown rash all over the body for 3 to 4 months. The histopathology of the cutaneous lesions and pleural effusion aspirate confirmed the diagnosis of Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL). While KS is one of the AIDS-defining illnesses seen in immunocompromised patients having low CD4 count, PEL is a rare and distinct subset of AIDS-related lymphoma. Despite the widespread availability of HIV testing, HIV diagnosis gets delayed due to stigma among MSM. This case report emphasizes the importance of early suspicion for symptoms of HIV-associated opportunistic infections in high-risk populations like MSM. The report reiterates the need for an ambient stigma-free environment for improving HIV screening in this high-risk population.

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

BackgroundA 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.MethodsWe 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).ResultsThe 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.ConclusionsThe 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.

PB2107: CLINICAL MANIFESTATIONS AND EFFICACY ANALYSIS OF 71 CASES OF AIDS-RELATED LYMPHOMA

Background: Patients with AIDS-related lymphoma (ARL) is difficult to accept standard treatment for various reasons. Aims: To summarize the clinical characteristics of AIDS-related lymphoma (ARL) patients admitted to Chongqing Cancer Hospital and improve the understanding of the disease. Methods: The clinical data of 71 ARL patients admitted from January 2008 to January 2021 were retrospectively analyzed. Results: The ratio of male to female in 71 ARL patients was 6.1:1, and the median age was 50 years. Fifty-one percent of patients had no other HIV-related manifestations and were only found at the time of lymphoma diagnosis. 20% of patients were diagnosed with lymphoma within 1 year of AIDS diagnosis and antiviral therapy. At the time of diagnosis of lymphoma, 35 cases (49.3%) with CD4+ cell count>200×10^6/L, 22 cases (30.9%) with CD4+ cell count 100-200×10^6/L, and CD4+ cell count<100×10^6/L and 6 cases of <50×10^6/L (accounting for 8.5 ), and 2 other cases are unknown. The most common pathological type in the 71 patients was diffuse large B-cell lymphoma (38 cases, accounting for 53.5%), Burkitt lymphoma (13 cases, accounting for 18.3), and the types also include Hodgkin lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, follicular lymphoma, marginal zone B-cell lymphoma tumor, CLL/SLL, T lymphoblastic lymphoma and Castleman disease. Thirty patients (42.3%) had extranodal involvement at the initial diagnosis, including lung, kidney, intestinal, pancreas, breast, testis, skin and soft tissue involvement. Ann-Arbor staging included 56 patients (78.8%) with stage III-IV, and 19 patients (26.8%) with B symptoms. Survival analysis showed that patients with central involvement, elevated LDH, and intermediate-high-risk IPI scores had shorter progression-free survival, and patients with large masses, intermediate-high-risk and high-risk IPI scores had shorter overall survival. Both CHOP and EPOCH-based chemotherapy regimens are used in AIDS-related non-Hodgkin lymphoma, but the efficacy varies greatly. ABVD treatment of AIDS-related Hodgkin lymphoma is effective, but extranodal involvement may be a poor prognostic factor. Summary/Conclusion: ARL has diverse clinical manifestations, frequent extranodal involvement, late clinical stage, high malignancy, and poor clinical efficacy.

Hypoalbuminemia predicts inferior outcome in patients with AIDS-related lymphoma

BackgroundThe prognostic value of serum albumin in acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) remains covered.MethodsWe retrospectively analyzed de novo ARL patients from 2013 to 2019 across three centers. Factors correlated with progression-free survival (PFS) and overall survival (OS) were evaluated in Kaplan–Meier, univariate and multivariate Cox proportional hazard models.ResultsA total of 86 ARL patients were enrolled with a median follow-up of 34 months. In the cohort, the OS and 2-year PFS rates were 37.5% and 35.4%, respectively. In multivariate models, older age (PFS, hazard ratios [HR] = 1.035, p = 0.037; OS, HR = 1.034, p = 0.041) and hypoalbuminemia (OS, HR = 0.910, p = 0.038) predicted inferior survival. ARL patients with hypoalbuminemia showed worse OS and 2-year PFS (p = 0.028 and p = 0.01, respectively), which was associated with poor Eastern Cooperative Oncology Group performance status (ECOG PS) and higher International Prognosis Index (IPI) score.ConclusionIn conclusion, serum albumin at diagnosis is an independent prognostic factor for overall survival in AIDS-related lymphoma.

Plasma extracellular vesicles bearing PD-L1, CD40, CD40L or TNF-RII are significantly reduced after treatment of AIDS-NHL

Emerging evidence shows that tumor cells secrete extracellular vesicles (EVs) that carry bioactive cell surface markers, such as programmed death-ligand 1 (PD-L1), which can modulate immune responses and inhibit anti-tumor responses, potentially playing a role in lymphomagenesis and in promoting the growth of these cancers. In this study, we investigated the role of EVs expressing cell surface molecules associated with B cell activation and immune regulation. We measured levels of EVs derived from plasma from 57 subjects with AIDS-related non-Hodgkin lymphoma (AIDS-NHL) enrolled in the AIDS Malignancies Consortium (AMC) 034 clinical trial at baseline and post-treatment with rituximab plus concurrent infusional EPOCH chemotherapy. We found that plasma levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII were significantly reduced after cancer treatment. AIDS-NHL patients with the diffuse large B cell lymphoma (DLBCL) tumor subtype had decreased plasma levels of EVs bearing PD-L1, compared to those with Burkitt’s lymphoma. CD40, CD40L and TNF-RII-expressing EVs showed a significant positive correlation with plasma levels of IL-10, CXCL13, sCD25, sTNF-RII and IL-18. Our results suggest that patients with AIDS-NHL have higher levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII in circulation before cancer treatment and that levels of these EVs are associated with levels of biomarkers of microbial translocation and inflammation.

Midkine inhibitor (iMDK) induces apoptosis of primary effusion lymphoma via G2/M cell cycle arrest

Primary effusion lymphoma (PEL) is an aggressive B-cell non-Hodgkin lymphoma in immunocompromised individuals such as AIDS patients. PEL shows a poor prognosis (median survival time < 6 months) compared with other AIDS-related lymphomas, and is generally resistant to conventional treatments. Novel drugs for PEL treatment are required. Midkine inhibitor (iMDK) was previously found to suppress midkine protein expression. Interestingly, iMDK suppressed cell proliferation in PEL cell lines in a time- and dose-dependent manner, regardless of midkine gene expression. We examined the mechanism of iMDK on PEL. Importantly, iMDK strongly induced cell cycle arrest at the G2/M phase within 12 h of incubation and suppressed the p-CDK1 protein level, which is associated with the cell cycle checkpoint at G2/M, resulting in mitotic catastrophe with observation of multipolar division. After mitotic catastrophe, iMDK-treated PEL showed apoptosis with caspase-3, − 8, and − 9 activation at 24 h incubation. However, iMDK showed no effects on viral protein-activated signaling pathways such as JAK-STAT, PI3K-Akt and NF-κB, and HHV-8/KSHV gene expression in PEL. These results indicate that iMDK is a novel CDK1 inhibitor and a promising lead compound for PEL chemotherapy treatment.

Frequency, Histologic, and Prognostic Significance of CD30 Expression in AIDS-associated Diffuse Large B-Cell Lymphoma

Introduction: AIDS-related Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with a variable response to chemotherapy depending on, and not limited to, cell of origin, double/triple hit, or MYC/BCL-2 co-expression status. Similar to DLBCL, AIDS-related DLBCL (ARL) with non-germinal center histology or MYC expression reports poorer response to treatment. In the immunocompetent population CD30+ DLBCL defines a histology with improved survival, however, the characteristics and outcomes of ARL expressing CD30 are not well studied.Methods: We assessed 3 cohorts of ARL. The first cohort, consisted of of an immunohistochemistry tissue microarray (TMA) of 30 ARL patients, followed by two validation cohorts. The first validation was a TMA of 80 ARL, from the AIDS Cancer Specimen Resource. Both TMAs were stained for CD10, BCL6, MUM1, CD20, Ki67, EBER, MYC (by IHC) cut off at 40%, BCL2 (by IHC) cut off 50%, and CD30 (considered positive if any CD30 was expressed on the malignant cells). The third validation cohort was from the County Hospital AIDS Malignancy Project (CHAMP), a prospective database of patients with hematological malignancies and HIV. Of the 100 cases with ARL, only 25 cases were found to have CD30 staining performed, thus only those cases were included. In total, 135 patients diagnosed with ARL were assessed. Cell of origin and germinal (GCB) vs. non-germinal center (NGC) was determined by the Hans algorithm. Statistical differences between groups were analyzed by the fisher exact test. Survival data, when available, was estimated using the Kaplan-Meier method and compared using the log-rank test.Results: Of the 135 ARL, 30% (n=41) were CD30+. Ninety-one% of the cohort was male. EBER was 23% positive in the entire cohort (n=29/126). EBER was positive in the CD30+ vs. CD30- population, 59% (N=17) vs 26% (p<0.01). Despite 59% of the CD30+ population being EBER positive, 92% of the population had a NGC phenotype, 2% was germinal, and 5% had a null phenotype (p<0.01). Of the 86 patients that were CD30-, 88% were GC vs. 12% NGC (P<0.01). The CD4+ T-cell count at presentation was higher in the CD30- cohort with a mean CD4+ T-cell count of 234 vs.164 cells/ul (p<0.05), similar to historical studies demonstrating a similar effect in germinal vs. non-germinal center ARL. Ki67 > 80% was also higher in the CD30- vs the CD30+ cohort 75 vs.60%, (p=0.052). Myc, BCL2, and double expressor lymphomas were identified 59 vs. 57%, 59 vs. 57%, and 31 vs. 28%, respectively, in the CD30+ ARL vs. the CD30- population, none were statistically significant. Survival data was only obtained for 56 of the patients. In the patients treated in the combined anti-retroviral era (ART), there was no difference in survival in the CD30+ vs. CD30- population, 74% (n=18) vs. 84% (n=12) at 5 years (p=0.8). In the 15 patients treated in the early ART era, the OS at 5 years was 48% for the CD30+ vs. 52% (p=0.4), the rest were treated in the pre-ART era.Conclusion: CD30+ ARL in this cohort represents 30% of all ARL evaluated, and presents almost exclusively as a non-germinal center phenotype and has a strong correlation with EBV. While no differences in survival were identified in this study, possible due to the small numbers of patients assessed with survival data, historically, NGC ARL have been shown to have poorer outcomes, by 20-30% in studies with da-EPOCH. As such, the need for better therapies, potentially to overcome these poor prognostic factors, should be studied further. [Display omitted] DisclosuresReid: ADC Therapeutics: Other: Serves as Principle Investigator, Research Funding; Aptose Biosciences: Other: Serves as Principle Investigator, Research Funding; Millennium Pharmaceuticals: Other: Serves as Principle Investigator, Research Funding; Xencor: Other: Serves as Principle Investigator.

Prognostic nomogram incorporating radiological features for predicting overall survival in patients with AIDS-related non-Hodgkin lymphoma.

Background:Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL).Methods:A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan–Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups.Results:In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/μL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer–Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome.Conclusion:A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.