[Malignant melanoma after bilateral retinoblastoma].
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Adult↗
Biomedical subjects
J M Tourani
Publications and source records attributed to J M Tourani.
Biologic response to anti-CD16 monoclonal antibody therapy in a human immunodeficiency virus-related immune thrombocytopenic purpura patient.
A patient with refractory human immunodeficiency virus (HIV)-related immune thrombocytopenic purpura (ITP) was treated with 3G8 (anti-CD16) monoclonal antibody on days 1, 3, and 8 (25, 25, and 50 mg were administered intravenously, respectively). Side effects were those expected after the administration of a xenogenic protein, but a severe bone pain occurred from the second injection. At the time of the initiation of the treatment the platelet count was 20,000/mm3 and the absolute CD4 number was 100/mm3. We obtained a long-term correction of thrombocytopenia and, to a lesser extent, there was a stabilization of CD4 lymphocytes for 18 months. We observed a significant stimulation of natural killer (NK) function and an elevation in the serum level of tumor necrosis factor alpha, interferon gamma, and granulocyte-macrophage colony-stimulating factor. This suggests that in HIV-related ITP the removal of platelets is mediated by low-affinity Fc gamma receptors (CD16). The stimulation of NK function and elevation in CD4+ lymphocytes may be related to the production of cytokines by activated human NK cells through the interaction of their CD16-bearing receptor with the 3G8 monoclonal antibody. This observation warrants confirmation and further clinical trials.
Acquired Immunodeficiency Syndrome↗
Chemoimmunotherapy of metastatic malignant melanoma. The Salpétrière Hospital (SOMPS) experience.
Optimistic results were obtained in the treatment of 39 patients with surgically incurable metastatic malignant melanoma using a regimen including 2 to 3 monthly induction cycles of cis-diamminedichloroplatinum (CDDP), recombinant interleukin-2 (rIL-2) and interferon alpha-2a (IFN alpha-2a). 33 of 39 patients were pretreated with chemotherapy (dacarbazine and/or fotemustine:31, CDDP:6) and 17 of 39 with IFN alpha-2a. Overall response rate was 54% with 13% achieving a complete response for up to 59+ weeks. Moderate to severe side-effects were reversible on rIL-2 cessation and toxicity was manageable in a routine inpatient setting. These results are especially encouraging as they were seen in previously treated patients, classically low responders, including 3 who were resistant to cisplatin or other platinum complexes. The question remains if this regimen bypasses traditional mechanisms of drug resistance.
Adult↗
High concentration of peripheral blood mononuclear cells harboring infectious virus correlates with rapid progression of human immunodeficiency virus type 1-related diseases.
In a cohort of 103 asymptomatic seropositive subjects (Centers for Disease Control and Prevention [CDC] stage II/III) followed for 2 years, the concentration of peripheral blood mononuclear cells harboring infectious human immunodeficiency virus (HIV) type 1 (viral burden) was correlated with the rate of decrease of CD4 cell count (RD-CD4; R = .857). Rapidly progressing patients (RD-CD4 > or = 60%; n = 18) had a high viral burden (mean +/- SE, 572 +/- 202 cells/mL) and an 89% progression to CDC IV-A-C, while stable patients (RD-CD4 < 30%; n = 55) had a low viral burden (mean +/- SE, 28 +/- 4 cells/mL) and remained asymptomatic. Slowly progressing patients (RD-CD4 > or = 30 and < 60%; n = 30) showed an intermediate viral burden (mean +/- SE, 131 +/- 9 cells/mL) and a 10% CDC IV-A-C progression. Quantitative determination of infectious virus in blood cells adds important information on the prognosis of HIV-1 infection.
Adult↗
Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors.
BACKGROUND: The first cases of Hodgkin's disease (HD) associated with HIV infection were reported in 1984. Since then, short series of seropositive patients suffering from HD have been published. In order to identify the characteristics, treatment response and outcome of HIV-associated Hodgkin's disease (HIV-HD), the data of HIV-HD patients recorded between 1987 and 1989 were analysed and compared with those of primary HD patient and with those of HIV-associated non-Hodgkin's lymphoma (HIV-NHL), registered during the same period. PATIENTS AND METHODS: The 45 cases of HD collected by the French registry of HIV-associated tumors between January 1987 and December 1989 were included in this study. All patients were clinically staged according to the Ann Arbor system. To compare HIV-HD characteristics with those of primary HD, we used a cohort of 407 patients with clinical stages (CS) IA to IVB, who were enrolled between September 1981 and August 1988 in a multicentric clinical trial. To identify the relationship between HIV-HD and the course of HIV infection we studied, when available, the routes of infection, initial CD4 cell count at the moment of HD diagnostic as well as the CDC class of HIV infection and compared these data with the same parameters observed in 142 HIV-NHL enrolled in the registry during the same period. RESULTS: HIV-HD is characterized by an increase in mixed-cellularity histology (49%), with a predominance of advanced stages (75%) and B symptoms (80%). A unique observation is made regarding mediastinal involvement, present in only 13% of HIV-HD (71% in primary HD). The HIV-HD/HIV-NHL ratio was significantly higher in intravenous drug abusers than in male homosexuals. Median CD4 cell count was 306/microliters at HIV-HD diagnosis, and only 11% of the cases were preceded by an AIDS manifestation. With standard therapy, 79% of the patients achieved complete remission, but hematological and infectious complications were very frequent. The progression to AIDS rate was 94% at two years and opportunistic infections were the most frequent cause of death. Overall two-year survival was 41% with 71% for patients with initial CD 4 cell counts higher than 300/microliter and 0% for those with CD4 cell counts lower than 300/microliter (P < 0.01). CONCLUSION: HIV-HD has a particular clinico-pathological profile when compared to primary HD, with a predominance of mixed-cellularity type, a high frequency of advanced stages and a high proportion of patients without mediastinal involvement. Moreover, HIV-HD seems to occur preferentially in the group of subjects infected by needle sharing. Standard HD therapy seems to be efficient but excessively toxic.
Adolescent↗
Lack of isolate-specific neutralizing activity is correlated with an increased viral burden in rapidly progressing HIV-1-infected patients.
OBJECTIVE: To delineate the interaction between in vivo HIV replication and host antiviral immunity during disease progression in order to elucidate the pathogenesis of AIDS. DESIGN: In a cohort of HIV-seropositive patients, the serum concentration of viral particles, the blood concentration of mononuclear cells harbouring infectious virus and the serum titre of isolate-specific neutralizing antibodies were correlated with the rates of CD4+ T-cell depletion and disease progression. METHODS: Using a quantitative reverse-transcriptase linked polymerase chain reaction assay, the concentration of viral particles was measured in blood samples from 103 initially symptom-free subjects who were followed up for > or = 24 months. The concentration of infectious virus and the neutralizing antibodies to autologous HIV isolates were assessed in 37 out of the 103 subjects. The rate of decrease in CD4 cells over the 24 months was calculated for each subject. RESULTS: Rapidly progressing patients (rate of decrease in CD4 cells > or = 60%) had a high concentration of viral particles and a high concentration of infectious virus associated with an undetectable serum titre of isolate-specific neutralizing antibodies. Stable patients (rate of decrease in CD4 cells < 30%) had a low concentration of infectious virus and either a low concentration of viral particles with the absence of isolate-specific neutralizing antibodies or a high concentration of viral particles with the presence of isolate-specific neutralizing antibodies. Slowly progressing patients (rate of decrease in CD4 cells > or = 30 and < 60%) showed an intermediate profile. CONCLUSIONS: Progression to AIDS is associated with a shift in the balance between viral replication and host immunity that increases the concentration of infected cells and destroys the CD4+ T-lymphocyte population.
Acquired Immunodeficiency Syndrome↗
Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.
PURPOSE: To evaluate the activity and the toxicity of the combination of cisplatin (CDDP)/recombinant interleukin-2 (rIL-2) and interferon alfa-2a (IFN alpha) in disseminated malignant melanoma (DMM). PATIENTS AND METHODS: Between December 1990 and March 1992, 39 patients with biopsy-proven metastatic malignant melanoma (MM), bidimensionally measurable lesions and an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 entered this protocol. Seventy-nine percent had received previous chemotherapy including platinum complex (15%) and alpha interferon (44%). They received CDDP (100 mg/m2 on day 0) followed by IL-2 18.10(6) IU/m2/d continuous intravenous (IV) infusion from day 3 to day 6 and from day 17 to day 21. The cycle was repeated on day 28. Subcutaneous IFN alpha 9.10(6) IU three times weekly was administered throughout the treatment period. From day 66 or 94, patients were administered a maintenance cycle with CDDP 100 mg/m2, subcutaneous IL-2 5.10(6) IU/m2/d from day 15 to day 19 and from day 22 to day 26 and IFN alpha 9.10(6) IU three times weekly repeated every 5 weeks (maximum four cycles). RESULTS: Among 39 assessable patients, five patients achieved complete responses (CRs). Sixteen patients had partial responses (PRs). The overall objective response rate was 53.8%. The number of metastatic sites was the only response-predictive factor. Toxicity was manageable in a routine patient setting and there was no life-threatening toxicity. CONCLUSION: These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.
Adult↗
Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.
Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials.
Adult↗
Elevation of IgE in HIV-infected subjects: a marker of poor prognosis.
The IgE synthesis is tightly controlled by a complex network of T and B cells. Because human immunodeficiency virus (HIV) disease associates T cell activation and depletion, polyclonal B cell activation, atopic symptoms, drug hypersensitivity, and autoimmune activity, we have evaluated IgE, as well as IgA, IgG, and IgM, in 315 HIV-seropositive individuals with or without acquired immunodeficiency syndrome (AIDS) and compared the results to those of 100 HIV-seronegative subjects. IgE levels were higher in HIV-infected subjects as a whole, compared to levels in seronegative control subjects (p less than 0.05). This difference was particularly marked between patients with AIDS and control subjects (p less than 0.005). A strong relationship appeared between IgE and the immune status as assessed by CD4 cell counts (p less than 0.001 between IgE values in patients with CD4 less than 300 or greater than 300/microliters). In addition, we assessed the predictive value of IgE elevation over disease progression: in subjects with a CD4 count less than 300/microliters, the survival analysis disclosed a 24-month occurrence rate of AIDS of 83% in individuals with IgE greater than 150 KIU/L versus 44% in individuals with IgE less than 150 (p = 0.016). In subjects with an AIDS-related complex, IgE greater than 150 indicated a 100% rate of AIDS versus 9% in individuals with IgE less than 150 (p = 0.003). Thus, IgE levels appear to be a very discriminative marker between patients in late stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease.
PURPOSE: For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS: Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS: At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION: The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.
Adolescent↗
Interleukin-2 therapy with or without lymphokine-activated killer-cell infusions for low-grade non-Hodgkin's lymphomas?
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Combined Modality Therapy↗
[Hodgkin's disease associated with HIV infection: clinical characteristics and development. French registry of tumors associated with HIV infection].
From May 1987 to July 1990, 45 cases of Hodgkin's disease (HD) were recorded by the French Registry of HIV-associated tumors. Thirty-nine patients were male and median age was 30 years. Twenty-two cases had mixed cellularity type (MC), 18 nodular sclerosis, two lymphocyte depletion and three were not classified. Thirty-four patients had advanced HD clinical stages (CS III and IV). Thirty-six patients (80%) presented with B symptoms. Bone marrow involvement was diagnosed in 12 patients. Mediastinal involvement was present in only 4/30 patients (12%). Risk groups for AIDS were homosexuality in 18 cases, intravenous drug abuse in 17, both in one, and other in nine cases. In 40 cases (89%), HD occurred before any AIDS-related episode. Median CD4 cell count at HD diagnosis was 304 cells/microliters. Seventy-nine percent of the patients achieved complete remission with standard therapy, but hematological and infectious complications were very frequent. The rate of progression to AIDS was 71% at three years and opportunistic infections (mainly pneumocystis carinii pneumonia) were the most frequent cause of death. Overall two-year survival was 41% (78% for patients with initial CD4 cell count higher than 300 cell/microliters and 0% for those with CD4 cell count lower than 300/microliters). HD-HIV has a specific clinical profile as compared to primary HD, with a predominance of MC type and advanced clinical stage, without mediastinal involvement (88%). This study provides a basis for future clinical trials on HD-HIV: intensity of chemotherapy should be adapted to CD4 cell count; pneumocystis carinii prophylaxis is mandatory in all cases. Zidovudine should be included during and after HD treatment; the potential role of hematological growth factors has still to be evaluated.
Acquired Immunodeficiency Syndrome↗
[Small cell lung cancers: intensive and short chemotherapy followed by irradiation. Results of a pilot study].
Twenty-six patients with localized small cell lung cancer received 3 monthly courses of intensive chemotherapy consisting of cisplatin (40 mg/m2/day on days 1, 2, 3), cyclophosphamide (750 mg/m2/day on days 4 and 5), adriamycin (50 mg/m2/day on day 5), vindesine (2 mg/m2/day on days 1 and 5), etoposide (100 mg/m2/day on days 1, 2, 3) and methylprednisolone (120 mg/m2/day on days 1 to 5). The first 10 patients received radiotherapy of the chest (3 Gy/day on days 7 and 8) and brain (2 Gy/day on days 7 and 8) after each course of chemotherapy, followed by complementary chest (27 Gy) and brain (22 Gy) radiotherapy after the end of the aplasia induced by the 3rd course of chemo-radiotherapy (alternate protocol: AP). In view of the toxicity of this protocol (4 deaths) and of the occurrence of 2 epidural relapses, the remaining 16 patients received the same 3 courses of chemotherapy followed by radiotherapy of the chest (55 Gy), brain (34 Gy) and spinal cord (34 Gy) (sequential protocol: SP). Haematological toxicity was controlled without problem in a medical oncology intensive care unit. The complete response rate (AP + SP) was 100 percent. The median survival rate was 26 months. Survival at 2 years was 20 percent with AP and 78 percent with SP (P = 0.002), this difference being due to the absence of iatrogenic deaths and epidural relapses. Intensive chemotherapy combined with radiotherapy deserves to be developed in the management of localized small cell lung cancer.
Actuarial Analysis↗
AIDS-associated non-Hodgkin lymphoma.
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Acquired Immunodeficiency Syndrome↗
Etoposide (VP 16-213) induced hepatitis. Report of three cases following standard-dose treatments.
Acute hepatitis is a potential, although rare, complication following administration of high doses of Etoposide (VP 16-213). We report three cases of severe hepatocellular necrosis following administration of standard doses of this antineoplastic agent.
Acute Disease↗
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↗
HIV-associated non-Hodgkin's lymphomas: clinical characteristics and outcome. The experience of the French Registry of HIV-associated tumors.
From 1/87 to 12/89, the French Registry of HIV-associated tumors recorded 131 cases of intermediate- and high-grade non-Hodgkin's lymphomas (NHL). There were 47 small non-cleaved Burkitt-type lymphomas (SNCL), 32 immunoblastic lymphomas (IL) and 52 diffuse large-cell or predominantly large-cell lymphomas (LCL). There were differences in the clinical patterns of the histological subtypes. Isolated extranodal presentation was less frequent in SNCL (2/47) than in IL (13/32) and LCL (17/49) (p less than 0.0001). In the latter two groups, the central nervous system was the principal site of extranodal involvement (16/30), 87% of SNCL, patients had no previous manifestations of AIDS whereas 40% of IL and LCL patients presented full-blown AIDS (p less than 0.01). At the time of NHL diagnosis, the median blood CD4 lymphocyte count was higher in SNCL (266/microL) than in LCL (125/microL, p less than 0.05) and IL (80/microL, p less than 0.01), 69% of stages I/II patients, 31% of stages III/IV, and 33% of stage ie patients achieved complete remission (CR), p less than 0.05. Overall median survival time was 5 months. There was no statistical difference in CR and survival rates among histological types. The two-year actuarial survival rate was 25% (median 8 months) for initially asymptomatic patients or those with persistent generalized lymphadenopathy (PGL) and 9% (median 3 months) for those previously with AIDS-related complex (ARC) and AIDS patients (p less than 0.001). Response to treatment was the other predictor factor. The two-year survival rate was 42% (median 16 months) for patients who achieved CR, and 5% (median 3 months) for those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Brain metastasis from malignant melanoma during interleukin-2 therapy].
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Brain Neoplasms↗