Factors in the development of AIDS-related lymphomas.
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Progressive polyradiculopathy is a rare, well-documented complication of the acquired immunodeficiency syndrome in man. It has been commonly attributed to a cytomegalovirus (CMV) infection. We report two HIV-infected patients with clinical and electrophysiological features of a unique, subacute, progressive polyradiculopathy. Post-mortem examination in case 1 disclosed an infiltration of the leptomeninges, the lumbar spinal cord, and the anterior and posterior roots by a B-cell immunoblastic lymphoma. Immunochemistry for HIV1 and CMV was negative in the peripheral and the central nervous system. Case 2 showed bone-marrow involvement by a Burkitt type lymphoma. Specific chemotherapy was followed by both clinical improvement of the polyradiculopathy and complete remission on a second bone-marrow biopsy. These findings may indicate that a lymphoma must also be considered a possible cause of polyradiculopathy in AIDS.
This report describes a clinical case of a large cell, immunoblastic plasmacytoid malignant B-cell lymphoma of the rectum in an AIDS patient coinfected with HTLV-I. The malignant cells showed clonal genetic rearrangement of the HC (JH) and LCK genes. Infection by EBV was demonstrated serologically and with slot blots using genomic DNA of the cancer cells. Southern blot analysis with DNA extracted from the lymphoma cells were negative for HTLV-I. The patient received seven cycles of VACO-B which induced complete but transient clinical remission of the tumor. The final outcome of the patient is unknown.
Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).
During the past 4 years, 122 patients with AIDS and 20 with thoracic lymphoma associated to AIDS were observed. There were 18 cases of non-Hodgkin's lymphoma, mostly at a high grade and a high b-cell stage (Burkitt's or Burkitt-like lymphoma) (16 cases). This prevalence reflects the general increase in the number of neoplasms secondary to immunosuppression, which goes along with the improvement of prevention and the control of opportunistic infections. Out of these 20 lymphomas in AIDS, 5 (25%) produced thoracic lesions; in 4 cases, the initial site of the disease was in a thoracic site. The frequency of such expressions is greater that reported in the literature. The radiological appearances are atypical relative to the classical signs of lymphoma in the general population, with predominantly nodular forms (60%) or peripheral, fast-growing masses that are likely to invade the thoracic wall. Isolate lymph node invasion is possible, as well as pleural effusion. Though not pathognomonic, this appearance is highly suggestive of lymphoma in AIDS (LDS) in HIV-positive patients. In all patients with pulmonary lymphoma, CT showed bilateral lesions in a greater number than plain radiography had shown, with morphological and CT appearances that allowed a correct approach of the diagnosis and an appropriate choice of the site of biopsy.
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The French-Italian Cooperative Study Group included patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma (NHL), defined as those with performance status (PS) > or = 3 and/or opportunistic infections (OI), in a prospective study with a 50% reduced-dose combination chemotherapy regimen: CHVmP-Vincristine-bleo (cyclophosphamide 300 mg/m2 i.v. day 1, doxorubicin 25 mg/m2 i.v. day 1, teniposide 30 mg/m2 i.v. day 1, prednisone 20 mg/m2 per os days 1-5, vincristine 2 mg i.v. day 15, and bleomycin 10 mg i.v. day 15), given every 21 days for eight cycles, and concomitant zidovudine 500 mg per os per day. The aims of this combined treatment were to reduce bone marrow toxicity and infectious complications related to chemotherapy (with a low-dose chemotherapy regimen), and to control the HIV and related infectious complications (with zidovudine therapy). Thirty-seven patients entered this prospective study. At the time of the NHL diagnosis, 41% of the patients had asymptomatic HIV infection, 27% had ARC and 32% had already had CDC-defined diagnoses of AIDS. The median CD4+ cell count was 35 mm3. Only 29 patients are evaluable for response, since 8 received only one cycle of chemotherapy. Fifteen of 29 (52%) patients obtained objective responses, with only 4 (14%) achieving complete remissions (CR) of 1, 4, 14 and 29+ months. Three (16%) CRs were achieved in 19 evaluable patients included in the study because of poor PS, and only one CR was observed in 10 evaluable patients with histories of OI, either alone or with poor PS. The most common side effect was bone marrow toxicity with 2 related toxic deaths.(ABSTRACT TRUNCATED AT 250 WORDS)
Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.
HIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lymphomas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and oncogenic viral coinfection. First-line therapy combines antiretroviral therapy (ART) with chemotherapy, achieving complete remission rates of 60-70% for DLBCL using R-EPOCH and 50-60% for BL with CODOX-M/IVAC. Relapsed/refractory cases show durable responses to CD19- CAR-T therapy; however, only 10% of HAL patients are enrolled in pivotal immunotherapy trials. Severe immunosuppression necessitates PET-CT-guided de-escalation and nanoparticlebased drug delivery systems to minimize toxicity. Emerging strategies include PD-1 inhibitors and broad-spectrum antivirals targeting HIV reservoirs, underscoring the need for precision medicine that integrates tumor genomics and viral dynamics.
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There are only a small number of specialized centres that cater for the dental care of the steadily increasing number of HIV-infected individuals. The responsibility will, therefore, be increasingly shared with the dental practitioner who should be knowledgeable on the basic oral management protocols involved in treating these individuals. This article summarizes some essentials of oral health care in HIV-infected individuals.
BACKGROUND: Epstein-Barr virus (EBV) is maintained as an episome in most infected cells. The presence of fused terminal restriction enzyme fragments distinguishes the circular DNA form from the linear virion form. METHODS: EBV genomic structure was analyzed in 8 lymphoid cell lines and 21 human lymphoma specimens by the Southern blot technique. RESULTS: Evidence of viral integration into host chromosomal DNA was identified in four cell lines. In the Namalwa and BL30-B95.8 cell lines, integration occurred through the terminal repeat (TR) sequences. In the BL41-P3HR1 and BL41-B95.8 cell lines, there was loss of left-end viral genomic sequences, including ori-P sequences required for episome maintenance, implying that integration was required for viral genome persistence. Integration was not detected in four other cell lines (Raji, Daudi, B95.8, and BL30-P3HR1). In 21 EBV-containing human lymphomas, including 18 immunodeficiency-related lymphomas, fused TR sequences were identified without evidence of viral genomic integration. CONCLUSIONS: These findings suggest that, although viral integration is common in Burkitt lymphoma cell lines infected in vitro, integration is not common in human lymphomas that develop in vivo in normal or immunodeficient people.
The DNA and nuclear antigens of Epstein-Barr virus (EBV) have been detected in specimens of tissue of non-Hodgkin lymphoma and lymphocytic interstitial pneumonitis from patients with acquired immunodeficiency syndrome. To determine whether there is serologic evidence of an active EBV infection in these disorders, we conducted a case-control study. The case patients were 10 children with acquired immunodeficiency syndrome and EBV genome-positive pneumonitis or lymphoma. We randomly selected one or, if available, two matched control patients with human immunodeficiency virus infection for each index patient and compared their EBV serologic profiles with those of the index case patient at the time of the biopsy. Ten case patients and 13 matched control patients were enrolled. All 10 case patients (100%) compared with 2 (15%) of 13 matched control patients had serologic evidence of either a primary or a reactivated EBV infection at the time the index patient had a biopsy performed (p less than 0.001). Therefore we found serologic and virologic evidence that EBV is etiologically related to EBV-associated lymphocytic interstitial pneumonitis and non-Hodgkin lymphoma in children with acquired immunodeficiency syndrome.
PURPOSE: A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS: DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS: The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS: EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.
Fourty-three primary cerebral lymphomas (PCL) were histologically classified and examined for genome expression of Epstein Barr Virus (EBV) and human herpes virus 6 (HHV6) using dot blotting, polymerase chain reaction, and Southern blotting. Only 20 tumors (16 high grade and 4 low grade lymphomas) could be suitably placed into a category of the Updated Kiel Classification, whereas the non-classified 23 tumors were highly malignant B-lymphomas and referred to as small-cell (SC) or large-cell (LC) blastic PCL. Most of the LC PCL showed a tumor-like infiltration pattern with high cellular density and little remaining parenchyma, whereas the SC PCL more often showed an inflammation-like pattern characterized by loose arrangement of tumor cells and marked astrocytic, microglial and T-lymphocytic reaction. EBV genome was found in 3/3 AIDS cases, but in none of 40 immunocompetent cases, while HHV6 was detected in 2 tumors of immunocompetent patients. We conclude that (1) the Updated Kiel Classification is not applicable to a majority of PCL, and (2) EBV and HHV6 do not appear to play a major role in the pathogenesis of PCL in immunocompetent subjects.
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