AIDS-associated non-Hodgkin lymphoma.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J M Andrieu
Publications and source records attributed to J M Andrieu.
Tumor necrosis factor production in HIV-seropositive subjects. Relationship with lung opportunistic infections and HIV expression in alveolar macrophages.
We have evaluated the TNF production by alveolar macrophages (AM) in 43 HIV-infected subjects in relation with 1) their clinical and biologic status; 2) the presence of lung opportunistic infections (OI); and 3) the expression of HIV by AM. This production was assessed in a standard chromium release test, using monocytic U937 cells as targets. The spontaneous TNF production by AM from patients without lung OI was higher than that from seronegative controls (p less than 0.02). This production by AM was similar to that of blood monocytes, suggesting that it was not related, in these subjects, to any particular lung status. The extent of TNF release by AM was correlated to the presence of a lymphocytic alveolitis (p less than 0.05), and not to the patients' clinical presentation nor to their CD4 cell count. Finally, AM from these subjects could be normally stimulated in vitro by IFN-gamma. On the other hand, it appeared that the spontaneous TNF release by AM shown in vitro to express HIV (p24+ AM) was significantly higher than that by their p24- counterparts (p less than 0.05) and by controls (p less than 0.01). In addition, contrasting with the marked increase of TNF release by p24- AM after their stimulation with IFN-gamma (p less than 0.001), p24+ AM appeared to be refractory to any stimulation by IFN, arguing for their activation in vivo. Finally, the spontaneous TNF release by AM was significantly increased during lung OI, compared with controls (p less than 0.01) as well as with AIDS patients without OI (p less than 0.01). In addition, the production of TNF by AM in these subjects was higher than that by the corresponding blood monocytes (p less than 0.02), suggesting a compartmentalization of this response within the lungs. In conclusion, it appears that the TNF production by AM of seropositive patients is highly related to the presence of lung OI as well as to the expression of HIV by these cells. In the context of the up-regulation of HIV expression induced by TNF in vitro, our data could suggest that the in vivo release of TNF by AM could participate in viral dissemination. Moreover, we hypothesize that the generation of activated AM refractory to any further stimulation could in turn lead to the development of additional pulmonary infections.
Gene Products, gag↗
Interleukin-2 therapy for refractory and relapsing lymphomas.
Recombinant interleukin-2 (rIL-2) has been reported to be active in metastatic renal cell carcinoma and malignant melanoma. The purpose of this trial was to determine the efficacy and toxicity of rIL-2 administered in continuous infusion in patients with Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL). 21 patients with HD (4 patients), diffuse large-cell NHL (7) or low-grade NHL (10) in failure or relapse after multiple-conventional treatments were included in this trial. rIL-2 therapy consisted of an induction period of two cycles separated by 3 weeks of rest, and, in the absence of progressive disease or undue toxicity, a maintenance period of 4 monthly cycles. Each induction cycle comprised the continuous infusion of rIL-2: 18 x 10(6) IU/m2 per day on days 1-5 and days 12-16. Each maintenance cycle comprised the continuous infusion of rIL-2: 18 x 10(6) IU/m2 per day on days 1-5. Among the 21 treated patients, 5 (all of those with low-grade NHL) responded to the induction phase (1 complete response, 4 partial responses) and 2 patients had a mixed response. Conversely, no response was observed in patients with HD or large-cell NHL. The median duration of response was 4 months. rIL-2 administered as a continuous infusion was well tolerated and most patients received the full dosage, and management did not require intensive care. During the induction period, 2 patients experienced grade III cardiovascular or renal toxicity. During the maintenance period, rIL-2 had to be interrupted in 1 patient because of a myocardial infarction. This trial confirms the inefficacy of rIL-2 for the treatment of large-cell NHL and HD. Conversely, in low-grade NHL, rIL-2 activity needs to be explored by further studies. rIL-2 may have a place in the early phase of the disease, when the immune system is not compromised, as an adjuvant treatment in residual disease in order to improve the duration of response.
Adult↗
Correlation between CD4 cell counts and cellular and plasma viral load in HIV-1-seropositive individuals.
We conducted a study of 152 HIV-1-seropositive individuals in order to evaluate the possible correlations between the isolation of HIV from peripheral blood mononuclear cells or from plasma and CD4 cell counts. HIV was isolated from only 36% of plasma samples, and the isolation rate was closely related to CD4 cell counts, increasing gradually from 0% in subjects with greater than 800 x 10(6)/l CD4 cells to 88% in those with less than 100 x 10(6)/l CD4 cells. In contrast, HIV was isolated from 92% of cell samples (99% in subjects with less than 900 x 10(6)/l CD4 cells, 46% in those with CD4 counts greater than or equal to 900 x 10(6)/l). Since most cell samples were positive, a scoring method was designed to quantify the cellular viral load. The results obtained demonstrated that the cellular viral load was closely related to CD4 counts. We also found that the cellular viral load was higher in subjects with either positive plasma isolation or positive p24 antigenaemia. The measurement of the cellular viral load by this scoring method appears to be useful for the management of HIV-seropositive individuals and for the evaluation of therapeutic trials.
CD4 Antigens↗
HIV isolation from pulmonary cells derived from bronchoalveolar lavage.
In a study of 75 alveolar cell co-cultures from 55 HIV-seropositive subjects, p24 antigen production was identified by ELISA in 11 out of 26 (42%) of unseparated cell cultures, 15 out of 39 (38%) purified alveolar macrophage cultures and eight out of 10 purified alveolar lymphocyte samples. Positivity in unseparated cell cultures was associated with an alveolar lymphocytosis greater than 30%. Negative macrophage cultures were significantly more likely in the early stages of HIV infection with none positive when the subject had a peripheral CD4+ cell count greater than 300/microliters. Alveolar macrophage infection thus appears to increase with HIV disease progression.
Bronchoalveolar Lavage Fluid↗
[Brain metastasis from malignant melanoma during interleukin-2 therapy].
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Brain Neoplasms↗
Hodgkin's disease in HIV-infected intravenous drug abusers.
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HIV Infections↗
Two cycles of cisplatin-vindesine and radiotherapy for localized nonsmall cell carcinoma of the lung (stage III). Results of a prospective trial with 149 patients.
One hundred forty-nine patients with localized nonsmall cell carcinoma of the lung (Stage III A and B) were treated with two monthly cycles of initial chemotherapy that included vindesine-cisplatin followed by 6000 cGy of thoracic irradiation. Patients with complete, partial, and minor response after initial chemotherapy were randomized into groups to receive either maintenance chemotherapy (four cycles) after radiotherapy or radiotherapy alone. The objective response rate was 24% after chemotherapy and 41% after combined chemoradiotherapy (complete response, 7.5%). The overall median survival was 9 months and the 2-year survival was 14%. Survival was identical with or without maintenance chemotherapy. The 2-year survival of patients with complete response was 75% compared with 9% for patients with partial or minor response. These results suggest that only the few patients (ten) who achieve complete response have a strong probability of survival. It is therefore essential to search for other therapeutic modalities that result in an increase of the complete response rate.
Adult↗
The induction of reciprocal translocations in mouse germ cells by chemicals and ionizing radiations. II. Combined effects of mitomycin C or thio-tepa with two doses of gamma-rays.
The combined effects of mitomycin C (MMC) and thio-tepa (TT) with gamma-ray doses of 5 and 9 Gy on mouse stem cells were studied using the spermatocyte test. Both chemicals induced very low yields of translocations after single treatments. In combined treatments with a dose of 5 Gy, a subadditive effect of MMC and an additive effect of TT were found. Combined with a dose of 9 Gy the compounds potentiated the effect of radiations. Up to now, most of the chemicals tested have shown additive effects when combined with doses of the ascending part of the dose-response curve and potentiating effects when combined with doses of its descending part. This has been considered additional confirmation of the concept that depletion of any kind of spermatogonia is sufficient to modify the genetic response of stem cells. However, the subadditive and additive responses found could be considered evidence that common biological mechanisms can modulate the response to combined treatments of chemicals and ionizing radiations.
Animals↗
The induction of reciprocal translocations in mouse germ cells by chemicals and ionizing radiations. III. Differential effect of two doses of adriamycin combined with 5 or 9 Gy of gamma-rays.
The induction of reciprocal translocations in mouse germ cells by combined treatments with chemicals and ionizing radiations has been studied. Male mice were intraperitoneally injected with doses of 5 or 10 mg/kg of adriamycin (ADR) and irradiated with doses of 5 or 9 Gy of gamma-rays 24 h later. Three types of response were found after analyzing diakinesis-metaphase I multivalent configurations: potentiation, with the dose of 5 mg/kg of ADR plus 9 Gy; subadditivity, with the dose of 5 mg/kg of ADR plus 5 Gy; and additivity, with the dose of 10 mg/kg of ADR plus 5 or 9 Gy. According to these results, the subadditive effect observed with the lower dose of ADR plus 5 Gy cannot be explained under the assumption that depletion of any kind of spermatogonia is sufficient for modifying the chromosomal response of stem cells to ionizing radiations. The role of DNA repair mechanisms modulating the response of spermatogonial cells to combined treatments is discussed under the assumption that some repair mechanisms can be triggered by treatment with a low dose of a chemical and these repair mechanisms can reduce cell mortality. Consequently, a higher frequency of more radioresistant cells can survive.
Animals↗
Changes of soluble CD16 levels in serum of HIV-infected patients: correlation with clinical and biologic prognostic factors.
The modulation of soluble CD16 titers in human immunodeficiency virus (HIV)-infected patients' serum, with an initial increase in Centers for Disease Control (CDC) clinical stage II and III patients followed by a dramatic drop in patients with AIDS (CDC clinical stage IV), is reported. These changes are statistically correlated with the CDC staging system, the number of CD4+ cells, the amount of p24 antigen in serum, and the anti-p24 antibody titers, indicating the potential value of soluble CD16 titer as an easily available serum marker of disease progression. To evaluate a possible link between this observation and the expression of membrane-associated CD16/FcRIII, flow cytometry immunofluorescence analysis was performed on peripheral blood lymphocytes from patients in three CDC stages; no specific changes in the number of natural killer cells expressing CD16+ antigens or in the total number of Leu19+ cells were found. However, there was a statistical correlation between the absolute number of T cells expressing CD16 antigens (CD3+/CD16+) and the modulated titers of soluble CD16 in HIV-infected serum.
Adult↗
Actuarial rate of clinical and biological progression in a cohort of 250 HIV-1-seropositive subjects. Laennec HIV Study Group.
This study was undertaken to define the risk of AIDS in a cohort of 250 HIV-seropositive patients identified by their clinical and biological status. All patients were enrolled between October 1985 and March 1988. They were classified according to clinical classes A, asymptomatic (n = 97); B, lymphadenopathic (n = 123); and C, AIDS-related complex, (n = 30). Also as CD4 cell stages 1 (CD4 greater than or equal to 600/microliters; n = 126); 2 (CD4 less than 600 and greater than or equal to 300/microliters; n = 83); and 3 (CD4 less than 300/microliters; n = 41); and serum p24 antigen positive (n = 48) or negative (n = 202). All patients were evaluated every 3-6 months, until AIDS development or April 1989: 29 cases of AIDS occurred during the follow-up period. The risk of AIDS in class C is very high (64% at 2 years) compared with the 3-year risk of classes A (13%) and B (25%). On the other hand the three CD4 stages have significantly different prognosis (stage 1 6%; stage 2 22%; and stage 3 89%; P less than 10(-2]. Antigen p24 negative and positive patients have also different prognosis (18% and 53%; P less than 10(-4]. Interestingly, p24 antigen conserved its prognostic value in stage 2 (positive 37%, negative 16%) while stages 1 are at low risk of AIDS and stages 3 at high risk whatever their p24 antigen status. We have also identified the risk of becoming stage 3 and/or p24 antigen positive in p24 antigen negative patients at stages 1 and 2 (respectively, 18% and 47%). This classification should serve to design randomized trials better with experimental drugs with earlier end-points than AIDS onset.
Acquired Immunodeficiency Syndrome↗
Autoreactive cytotoxicity in HIV-infected individuals.
A possible role for autoimmunity in the pathogenesis of HIV infection has been suggested, based upon the certain degree of homology shared by HIV gp41 and MHC class II molecules. A number of humoral markers of autoimmunity have since been found in seropositive subjects. We have evaluated the cellular autoreactive response in HIV-infected individuals. Our study demonstrates the existence of a cytolytic activity, present in seropositive but not in seronegative subjects. This activity is mediated by CD3+ T cells, which only occasionally express the CD8 or the CD4 surface markers. Effector cells do not appear to exert their activity in a MHC-restricted fashion, since allogeneic target cells could also be killed, recovered from allogeneic seropositive as well as from seronegative subjects. Several types of target cells were lysed: T cell blasts and Epstein-Barr virus (EBV) transformed B cells, suggesting that the target antigen is common to at least these two cell types. The fact that cells from seronegative individuals were lysed argues against the recognition of an HIV-specific antigen. The nature of the target determinants and the identity of the effector cells are discussed.
Antigens, CD↗
Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease.
The purpose of this study was to evaluate the influence of the number of mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) cycles and the extent of irradiation on the risk of secondary acute nonlymphocytic leukemia (SANLL) after a single combined treatment for Hodgkin's disease (HD). Between April 1972 and May 1980, 462 patients with HD clinical stage (CS) I, II, and III were prospectively treated with three or six cycles of MOPP and supra- and/or infradiaphragmatic irradiation (40 Gy). Four hundred forty-one patients achieved complete remission (CR). By January 1988, 237 patients had been followed-up in first CR for at least 10 years. Ten patients developed SANLL between the 34th and 123rd month of CR. The 15-year SANLL risk is 3.5% +/- 2.7%. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, histology, splenectomy, MOPP chemotherapy, and irradiation extent) showed that the only significant explanatory variable of SANLL risk was the irradiation extent (P less than .002). Using the log-rank test, SANLL risk ranged from 2.2% for supradiaphragmatic irradiation alone to 9.1% for subtotal (STNI) or total nodal irradiation (TNI) (P less than .001). These results strongly suggest that extended high-dose irradiation and MOPP chemotherapy should not be combined for the treatment of HD.
Adolescent↗
Cisplatin and vindesine for disseminated non-small cell lung cancer. Results of a prospective trial with 81 patients.
Eighty-one patients with disseminated non-small cell lung cancer (stage IV) were treated with 2 monthly cycles of initial chemotherapy combining cisplatin with vindesine. The initial chemotherapy-responding patients (CR, PR, MR) were randomized to 2 cycles or 4 cycles of maintenance chemotherapy. After initial chemotherapy, the response rate was 33% (CR, PR, MR) with 18.5% objective responses. The overall 1-year survival rate was 15% with 37% for responders as opposed to 2% for non-responders. Maintenance chemotherapy did not improve the response rate obtained after initial cycles. The small number of patients does not allow us to reach a definite conclusion on the optimum duration of maintenance chemotherapy. In the absence of large placebo versus chemotherapy randomized trials, no definite conclusion can be made on the benefit of chemotherapy in disseminated non-small cell lung cancer. This study suggests, however, that chemotherapy is associated with a significantly longer survival in responding patients.
Adult↗
Advanced Hodgkin disease (clinical stages IIIB and IV): low relapse rate after brief chemotherapy followed by high-dose total lymphoid irradiation.
From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high-dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment-related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse-free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation.
Adolescent↗
Complete remission following recombinant interferon alpha-2a in a patient with diffuse large B cell cutaneous lymphoma.
Recombinant interferon alpha (r IFN alpha) has shown significant antitumor activity in patients with follicular small cleaved cell (low-grade non-Hodgkin's lymphomas) and cutaneous T-cell lymphomas. However, IFN alpha seems to be less effective in patients with intermediate or high-grade lymphomas. This case report describes a patient with an initial diagnosis of low grade B-cell lymphoma with histologic conversion to diffuse large B-cell (B1+, Kappa+) cutaneous lymphoma. This tumor proved refractory to chemotherapy but a complete and durable remission was induced with R IFN alpha 2a treatment.
Adult↗
HIV-related hematological neoplasias in France.
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Acquired Immunodeficiency Syndrome↗