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.

Changing Patterns of Lymphoma in the Antiretroviral Therapy Era in Johannesburg, South Africa.

BACKGROUND: South Africa has a high HIV prevalence, which associates with an increased risk of lymphoma. Antiretroviral therapy (ART) became accessible in 2004, but the program has substantially expanded. Changes in lymphoma patterns are documented in high-income countries after wide-scale ART including declining high-grade B-cell non-Hodgkin lymphomas (HG B-NHLs), particularly diffuse large B-cell lymphoma, and increased Hodgkin lymphoma (HL). There are limited data from Africa. This study aimed to compare HG B-NHL characteristics in the early (2007) and later (2017) ART era. METHODS: All incident lymphomas at the National Health Laboratory Service, Johannesburg, were identified using the laboratory information system, and data were collected for each patient. RESULTS: The total number of lymphoma cases increased from 397 (2007) to 582 (2017). This was associated with improved lymphoma classification and patient referral for oncological care. HG B-NHL remained the most diagnosed lymphoma subtype in 2017 comprising 70% of HIV-associated lymphomas, followed by HL (24%). Diffuse large B-cell lymphoma comprised 65% of all HG B-NHLs and 45% of all lymphomas in people with HIV in 2017. Significantly more patients were on ART in 2017, with improvements in virological control documented. Despite this, 47.6% of patients were not virologically suppressed, and 37.5% of patients were ART-naive at time of diagnosis in 2017. Immunological reconstitution was suboptimal, which may reflect late initiation of ART. CONCLUSION: Public health initiatives to initiate ART as early as possible and to retain patients in ART programs may assist in decreasing the number of HIV-associated lymphomas in our setting.

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.

Secondary gastric lymphoma - Do we know its endoscopic findings?

No disponible

[Primary neurolymphomatosis in the cauda equina as the initial symptom of human immunodeficiency virus]. / Neurolinfomatosis primaria de cola de caballo como manifestacion inicial del virus de la inmunodeficiencia humana.

TITLE: Neurolinfomatosis primaria de cola de caballo como manifestacion inicial del virus de la inmunodeficiencia humana.

Plasmablastic lymphoma achieving sustained remission with antiretroviral therapy alone.

Despite advances in the treatment of most human immunodeficiency virus (HIV)-related lymphomas, the outcomes for patients with HIV-related plasmablastic lymphoma (PBL) remain poor. While studies have shown an increased survival for patients with most kinds of HIV-related lymphomas since the introduction of highly active antiretroviral therapy (HAART), the impact of HAART on survival in patients with HIV-related PBL is unclear, mainly because the condition is rare and the number of published studies is small. Few case reports have shown regression of PBL after initiation of HAART, however, usually followed by recurrence of PBL or achieved with a need for chemotherapy. We report the first case of PBL in a 38-year-old man with newly diagnosed HIV who achieved sustained remission after the initiation of HAART alone and who remains in remission seven years after diagnosis, without a need for chemotherapy or radiation. We illustrate the importance of initiating HAART therapy under the supervision of infectious disease specialists as soon as the PBL is diagnosed until future studies provide clear evidence in the management of HIV-related PBL.

Increasing Levels of Serum Heat Shock Protein 70 Precede the Development of AIDS-Defining Non-Hodgkin Lymphoma Among Carriers of HLA-B8-DR3.

BACKGROUND: We hypothesized that carriage of presumably high Hsp70-producing gene variants on a specific human major histocompatibility complex haplotype, the 8.1 ancestral haplotype (8.1AH), may predispose HIV-infected individuals to AIDS-non-Hodgkin lymphoma (NHL). SETTING: We compared serum Hsp70 levels in the years preceding the diagnosis of AIDS-NHL in a matched case-control study (n = 151 pairs) nested in the Multicenter AIDS Cohort Study. METHODS: We tested the impact of 8.1AH-specific single-nucleotide polymorphism (SNP) and joint SNP-human leukocyte antigen extended haplotypes previously associated with AIDS-NHL in the Multicenter AIDS Cohort Study on the circulating Hsp70 levels in mixed linear models. RESULTS: We report elevated serum levels of Hsp70 in the 4 years preceding the diagnosis of AIDS-NHL in cases that carry 8.1AH, but not in noncarrier cases and not in carrier- or non-carrier-matched controls. The strongest predictor of higher serum Hsp70 was the haplotype A-G-A-C formed by SNPs rs537160(A) and rs1270942(G) in the complement factor CFB gene cluster, and rs2072633(A) and rs6467(C) in nearby RDBP and CYP21A2 located 70 Kb apart from the Hsp70 gene cluster. The association with A-G-A-C haplotype (beta = 0.718; standard error = 0.182; P = 0.0002) and with other 8.1AH-specific haplotypes including the high-producing tumor necrosis factor-alpha haplotype rs909253(G)-rs1800629(A) (beta = 0.308; standard error = 0.140; P = 0.032) were observed only with NHL identified as an AIDS-defining condition, but not as a post-AIDS condition, nor in combined AIDS and post-AIDS cases. CONCLUSION: Our combined genetic and functional approach suggests that the altered level of Hsp70 is a correlate of 8.1AH-mediated AIDS-NHL. Further investigation of the Hsp70 gene cluster and nearby loci that are tagged by A-G-A-C could better elucidate the genetic determinants of the malignancy.

A longitudinal and cross-sectional study ofEpstein-Barr virus DNA load: a possible predictor of AIDS-related lymphoma in HIV-infected patients.

INTRODUCTION: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma. METHODS: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls). RESULTS: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis. CONCLUSIONS: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.

Derrame pericárdico maligno como presentación de sida: papel de la citometría de flujo en el diagnóstico precoz / Malignant pericardial effusion as a presentation of AIDS: the role of flow cytometry in early diagnosis

No disponible

The role of brain biopsy in the clinical management of HIV-related focal brain lesions.

OBJECTIVES: Up to 20% of HIV-related focal brain lesion (FBL) diagnoses cannot be determined without invasive procedures. In such cases, brain biopsy is an important step in the evaluation algorithm. The aims of this study were to describe the clinical outcomes of patients with FBL, the proportion of diagnoses confirmed by brain biopsies and their aetiologies, and to analyse the proportion of patients in whom the biopsy motivated a change in therapeutic management. METHODS: A retrospective cohort study was performed. The data from clinical records of patients with HIV-related FBL admitted between January 2005 and December 2015 were reviewed. RESULTS: A total of 137 patients were included in the study. The median age was 39 years [interquartile range (IQR) 33-44.5 years]. The median CD4 count was 54 cells/µL (IQR 21-124 cells/µL). Cerebral brain biopsy was performed in 21.16% of patients (29 of 137); 68.9% of these individuals (20 of 29) were diagnosed by histology, with results of central nervous system (CNS) lymphoma in 20.6% (six of 29), progressive multifocal leucoencephalopathy in 6.8% (two of 29), toxoplasmosis in 6.8% (two of 29), tuberculoma in 6.8% (two of 29), and other diagnoses in 27.6% (eight of 29). In nine patients, the histology was nonspecific. In 75.8% of patients (22 of 29), the result of the biopsy led to a change in the therapeutic management. We did not observe higher rates of mortality related to the procedure. Overall mortality at 30 and 90 days was similar in patients who were and were not biopsied. CONCLUSIONS: In this retrospective cohort study, cerebral biopsy was associated with significant adjustments in therapeutic management for a high percentage of patients.

Feasibility and Efficacy of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for HIV-Associated Lymphoma: A Single-Institution Experience.

BACKGROUND: HIV-associated lymphomas (HAL) remain an important cause of morbidity and mortality in HIV patients, especially in the setting of treatment-refractory disease. Hematopoietic cell transplantation (HCT) is considered a curative option for patients with refractory HAL. PATIENTS AND METHODS: We report the efficacy of autologous HCT in 20 patients with HAL [non-Hodgkin lymphoma = 14 (70%), Hodgkin lymphoma = 6 (30%)]. At the time of transplantation, the median peripheral blood CD4+ count was 226 cells/µL. HIV virus load was undetectable in 14 (70%) of 20 patients. RESULTS: The median follow-up of surviving patients was 47 months (range, 20-119 months). The median time to neutrophil engraftment was 11 days. The median progression-free survival and median overall survival have not been reached. At 4 years after transplantation, progression-free survival and overall survival were 65% and 70%, respectively. Six patients died from disease relapse or progression (n = 5) and infection (n = 1). Nonrelapse mortality was 0 and 5% at 100 days and 4 years after transplantation, respectively. CONCLUSION: Autologous HCT is an effective therapy for refractory/relapsed HAL with manageable toxicity, similar to non-HIV patients.

Malignant lymphoma in the HIV-positive patient.

The introduction of combination antiretroviral therapy (cART) drastically improved performance status, immune function, and life expectancy of HIV-infected individuals. In addition, incidence of opportunistic infections and of AIDS-defining malignancies declined. Nevertheless, aggressive non-Hodgkin's lymphoma still remains the leading cause of AIDS-related deaths. The availability of cART, however, significantly improved the therapeutic options for HIV-positive patients with lymphomas. Diffuse large B-cell lymphoma, Burkitt's lymphoma, or Hodgkin lymphoma has increasingly become curable diseases. In light of these favorable developments in the treatment of HIV and HIV-associated lymphomas, reduction in treatment-associated toxicities and further improvement of outcome of patients with advanced immune suppression are major requirements for future clinical trials. This review summarizes the current treatment landscape and gives an overview on future needs in HIV-positive patients with lymphoma.

Linfoma de Burkitt en un escolar con infección perinatal por VIH lentamente progresiva / Burkitt's lymphoma in a school boy with slow progression perinatally acquired HIV

Resumen Las manifestaciones clínicas en los niños con infección por el virus de la inmunodeficiencia humana (VIH) de transmisión perinatal, pueden ser de inicio precoz o tardío. El linfoma asociado a VIH es una manifestación tardía que se asocia a estadios avanzados de inmunosupresión. Se presenta el caso de un escolar de 9 años con diagnóstico de novo de infección por VIH que debutó con un linfoma de Burkitt. En niños, la frecuencia de esta asociación es de 1-2% con pocos casos reportados en la literatura médica.

Children with perinatal human immunodeficiency virus (HIV) infection can present early or late clinical disease. HIV-associated lymphoma is a later manifestation that is associated with advanced immunosuppression (acquired immunodeficiency syndrome -AIDS). This is a case of a 9-year-old boy with recent diagnosis of HIV with Burkitt's lymphoma as first clinical manifestation. In children, the frequency of this association is very low and there are few cases reported.

Linfoma primario de ano en un paciente con virus de la inmunodeficiencia humana/sida / Primary lymphoma of anus in a patient with human immunodeficiency virus/AIDS

Se presenta el caso clínico de un paciente de 47 años de edad con seropositividad del virus de inmunodeficiencia humana/sida desde hacía 5 años, quien acudió a la consulta de Cirugía en el Hospital Gubernamental de Mbabane en Suazilandia, por presentar un tumor anal; se diagnosticó hemorroides, pero el tumor continuó aumentando de tamaño, unido a sangrado e intenso dolor. Se realizó una biopsia por incisión que indicó la presencia de un linfoma de alto grado de malignidad. Posteriormente el paciente fue evaluado en la consulta de Oncología, donde se le indicaron los exámenes complementarios necesarios, los que revelaron que la neoplasia se encontraba en estadio IE; de manera que fue remitido a Sudáfrica para recibir quimioterapia combinada, con la cual desapareció la lesión maligna y se controló la enfermedad

The case report of a 47 years patient with the human immunodeficiency virus/AIDS for 5 years is presented. He went to the Surgery Service in the Government Hospital of Mbabane in Swaziland, due to an anus malignancy; hemorrhoids was diagnosed, but its size continued increasing, along with bleeding and acute pain. An incision biopsy that indicated the presence of a high grade lymphoma malignancy was carried out. Later on the patient was evaluated in the Oncology Service, where the necessary complementary exams were indicated, revealing that neoplasm was in IE stage; so he was referred to South Africa to receive combined chemotherapy, with which the malignant lesion disappeared and the disease was controlled

High frequency of identical clonal immunoglobulin DNA in pre-treatment tumor and plasma from untreated patients with HIV-associated lymphoma: prospective multicenter trial of the AIDS malignancies consortium (AMC 064).

Patients with HIV are at increased risk for developing B-cell lymphomas likely due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig) gene rearrangements. Next-generation sequencing (NGS)-based identification of circulating Ig clonotypes has not been well-characterized in HIV-related lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients with HIV-related B-cell lymphomas and analyzed paired tumor/plasma specimens for Ig clonotypes using an NGS approach (AMC064, NCT00981097). Lymphoma-specific clonotypes (>5% frequency) were identified in 83% (33/40) of tumor specimens. Results from paired tumor/plasma specimens showed identical circulating clonotypes in the plasma from 97% (32/33) of patients. High International Prognostic Index (IPI) scores of 3-4 among patients with B-cell lymphoma correlated with higher lymphoma molecules/million diploid genomes in the plasma compared with lower IPI scores of 0-2, median 77335 vs. 6876, p = .005. Further studies are merited to determine whether plasma clonal Ig DNA is prognostic in HIV-related lymphomas.