Long survival in patients with acquired immune deficiency syndrome-related primary central nervous system lymphoma.
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Biomedical subjects
Publications and source records attributed to E Vaccher.
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BACKGROUND: The optimal therapeutic approach for patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection is unknown. In an attempt to improve the results obtained with standard chemotherapy and to decrease the occurrence of opportunistic infections (OI) during chemotherapy and follow-up observed in a previous experience, the authors designed a prospective combined antineoplastic and antiretroviral approach. METHODS: Between March 1989 and March 1992, 17 consecutive previously untreated patients (median age, 30 years) with HD and HIV infection were enrolled. They had Stage III and IV or Stage I and II disease with adverse prognostic factors. The median CD4+ cell count was 184/microliters. Patients were stratified in two groups and treated accordingly. Group A was made up of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than 3 and without OI. These patients received epirubicin 70 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 IV on day 1, and vinblastine 6 mg/m2 IV on day 1 (regimen EBV). Group B was made up of patients with PS of 3 or greater or previous OI who had received a 50% reduced dose of epirubicin and vinblastine and a full dose of bleomycin. Courses were repeated every 21 days for six cycles. Zidovudine was given at the dose of 500 mg/day from the beginning of chemotherapy in Group B and after the third cycle in Group A. RESULTS: Overall, 14 of 17 (82%) patients had an objective response and 9 of 17 (53%) achieved a complete remission (CR) of disease for a median duration of 20 months. Toxicity was moderate with Grade 3-4 leukopenia in eight patients and Grade 3 thrombocytopenia in one patient. Thirteen of 17 patients received zidovudine as planned with a median duration of 9 months. Only one patient had OI during or after chemotherapy (median follow-up, 11 months). No worsening of HIV markers during the combined therapy was seen, with the median CD4+ cell count before and after therapy being 184/microliters and 203/microliters, respectively. The median survival time was 11 months, with an actuarial survival rate of 48% at 36 months. The median survival time for the nine patients with CR has not been reached at the time of this analysis. CONCLUSIONS: These results revealed the feasibility and the activity of the combination of EBV regimen and zidovudine. Objective response rate seems similar to those previously observed in patients receiving standard chemotherapy, but only one patient had OI, and this compares favorably with the 16 OI observed in 28 patients treated with standard chemotherapy (6% versus 57%) in the authors' previous experience. Thus, it seems that the addition of antiretroviral therapy to the EBV regimen decreased the occurrence of OI during chemotherapy or follow-up.
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BACKGROUND: Hodgkin's disease (HD) has been described in patients with HIV infection in association with unfavourable prognostic factors. Similarly, HD in the older general population has a poorer prognosis than in younger patients. PATIENTS AND METHODS: With the aim of comparing the clinicopathological features and survival of HD in HIV-infected patients and in the general population, we analysed 176 patients with HD from 1986 to 1992. We divided the 84 HIV-negative patients into two groups: group A included patients less than 55 years old, group B patients of 55 years or older. This division was made in order to compare HD in HIV-infected patients with the less favourable group of patients with HD in the general population, i.e., older patients. RESULTS: Patients of the older group and HIV-infected patients had a significantly lower frequency (31% and 21%, respectively) of nodular sclerosis subtype compared to the younger group (85%). Mixed cellularity (MC) is significantly more frequent both in the older group and in HIV-infected patients. Lymphocyte predominance is more frequent (16%) in older patients than in the other two groups. HIV-infected patients are more likely to show advanced stages, B symptoms, and extranodal involvement. Chemotherapy (CT) alone has been the most widely used (83%) treatment in HIV-infected patients, while CT plus radiotherapy (RT) has been mostly employed in the general population. Twelve (14%) HIV-infected patients did not receive any treatment. Complete remission was achieved in 51% of the cases in the HIV-infected patients, and around 90% of the cases in the general population. The estimated 4-year survival rate in the HIV-infected patients is much lower (33%) than in the other two groups (100% in group A, and 88% in group B). CONCLUSION: While MC is the most common histological subtype both in HIV-infected patients and in the older general population, HD in HIV-infected patients has a worse prognosis than in the older general population, not only because of underlying HIV infection, but also because of the more unfavourable clinicopathological features at presentation.
There is evidence that, in addition to Kaposi's sarcoma, high-grade non-Hodgkin's lymphoma, and invasive cervical carcinoma (the only malignancies diagnostic per se of AIDS), other tumors have been occurring in the HIV setting, often with peculiar clinicopathologic characteristics. Because the survival of patients with HIV infection has improved owing to the better prevention and management of opportunistic infections, it is highly likely that these malignancies will increase in the next few years. The study of these tumors will help us better understand the relationship between the prolonged immunosuppression and the development of tumors.
With the aim of comparing the clinical features of Burkitt's like lymphoma (BL) in HIV-infected patients and in the general population, we retrospectively analyzed 35 patients with HIV-positive non-Hodgkin's lymphoma (NHL) and 535 patients with HIV-negative NHL, from 1985 to 1990. A total of 33 patients with BL were diagnosed at our institute: 18 without and 15 with HIV infection; 3.3% and 43% of all HIV-seronegative and HIV-seropositive NHL respectively. No significant differences were found between these two series concerning clinical features, with the exception of peripheral adenopathy that was more common in the HIV infected patients (p = 0.05). In both groups BL was characterized by advanced stage and high incidence of bone marrow and gastrointestinal involvement. Response rate was lower in the HIV-positive patients, but the difference was not significant. No relevant differences in the toxicity after chemotherapy were observed. The median survival in the HIV-infected patients was lower (7 months) than in the other group (14 months), with borderline statistical significance (p = 0.06).
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A series of selected lymphoid malignancies (LMs) occurring in Italian HIV-1-infected (HIV+) patients, principally intravenous drug users, was investigated. In addition to small non-cleaved-cell (SNCC) and large-cell immunoblastic (LCI) non-Hodgkin's lymphomas (NHLs), a relatively high occurrence of anaplastic large-cell Ki-I-positive (ALC Ki-I+) lymphomas and Hodgkin's disease (HD) was observed, at variance with other reported series of HIV+ patients. Combined results of in situ hybridization and Southern-blot analyses, in conjunction with immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-I (LMP-I), showed an almost complete association of ALC Ki-I+ lymphomas and HD cases with EBV. The neoplastic cells of both these LMs also showed common immunophenotypic features such as frequent absence of B- and T-cell differentiation markers and expression of the Ki-I activation marker, while SNCC and LCI lymphomas were mainly of mature B-cell origin and Ki-I-. The concomitant high incidence of ALC Ki-I+ lymphomas and HD in a specific group of HIV+ patients, their almost complete association with EBV in clonal and episomal form and the great similarity in differentiation, activation and virological markers which they display suggest that these LMs are pathological variants of a continuous spectrum of HIV-I-associated disorders etiopathologically linked to EBV.
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Between December 1986 and December 1991, the Italian Cooperative Group on AIDS-related tumours documented 94 HIV related solid tumours. Of 21 germinal testicular tumours collected, ten were seminomas. Cervical carcinoma was observed observed in 28 IVDAs (intraepithelial in 8 and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in 14 patients. Also reported were two cases of colorectal carcinoma, one anorectal carcinoma, one pancreatic carcinoma, one carcinoid, one oral carcinoma. Of the central nervous system tumours, were diagnosed 3 cases of glioblastomas, one medulloblastoma and one meningioma. This retrospective study shows that while oral and anorectal tumours were very rarely observed, a wide spectrum of other HIV-related solid tumours were found in this series. The required therapeutic approaches may not necessarily be influenced by the HIV infection, in contrast with the observed pattern for treatment of EKS and lymphomas in HIV infected subjects.
In order to assess modes of human immunodeficiency virus (HIV) transmission from heterosexual intravenous drug users (IVDUs) to their partners, condom use and sexual habits with both steady and occasional partners were investigated. A total of 349 heterosexual IVDUs (247 men and 102 women) who ignored, at the time of interview, their HIV serostatus were interviewed. Respondents were asked for information on condom use and sexual habits for the three year period prior to the interview. Nearly 40% of IVDUs reported sexual intercourse with both steady partners and occasional partners. Fifty-four percent of their steady partners and 48% of their occasional partners were individuals who did not belong to groups at risk for HIV infection. Anal intercourse with steady partners was reported by 29% of IVDUs and 24% of IVDUs with occasional partners. Condom use during vaginal intercourse was seldom reported: 83% of IVDUs never used a condom with steady partners and 75% did not use one with occasional partners. IVDUs who were 1) unmarried, 2) enrolled in the study after 1986, 3) partners of not at-risk individuals, 4) partners of a foreigner and, 5) aware of their partners HIV seropositivity showed significantly higher, albeit still low, frequencies of condom use with steady partners. Conversely, all these factors seemed to have little impact on condom use with occasional partners. Condom use and sexual habits were similarly reported by HIV-positive and HIV-negative IVDUs. The present study shows that high-risk sexual behaviours among IVDUs are very widespread and it stresses the need for intensive counselling to promote condom use among IVDUs.
A report of a case of rapidly growing vulvar cancer associated with vulvar condylomas in a patient with HIV infection is given. This aggressive tumor resembles those epithelial tumors observed in women with iatrogenic immunosuppression and lymphoid neoplasia currently observed in HIV patients.
Ninety-two cases of Hodgkin's disease (HD) in patients with HIV infection have been collected by the Italian Cooperative Group on AIDS and Tumors (G.I.C.A.T.). In accordance with the epidemiology of HIV infection in Italy, 82% were intravenous drug users (IVDU), 8% homosexual men, 5% IVDU+homosexuals and 5% heterosexuals. At diagnosis of HD, 16% had AIDS, 20% AIDS related complex (ARC), 33% persistent generalized lymphadenopathy (PGL) and 31% were asymptomatic. Fifty-three percent of the patients had stage IV disease and 70% mixed cellularity and lymphocytic depletion. Forty-six patients were treated with MOPP or MOPP [symbol: see text] ABVD +/- radiotherapy (zidovudine was not given) with complete remission (CR) in 54% and partial remission (PR) in 46% of the patients. Fifty-six percent of these patients developed opportunistic infections (OI) during therapy or follow-up. Sixteen patients were treated with epirubicin, bleomycin and vinblastine (EBV) and concomitant zidovudine, with CR in 44% and PR in 38%. However, only one of these patients developed OI during therapy or follow-up. The clinico-pathological features and natural history of HD in HIV setting are peculiar and quite distinct from those observed in HD in the general population. Better combined chemotherapy and antiretroviral therapy is needed in order to ameliorate the CR rate and decrease the OI in patients with HIV infection and HD.
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)
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The clinicopathologic features of 45 human immunodeficiency virus (HIV)-infected patients (mainly intravenous drug users [IVDU]) with lymphoid neoplasias seen from September 1984 through July 1990 at an Italian cancer center are reviewed. Thirty-five had systemic non-Hodgkin's lymphoma (NHL), and ten had Hodgkin's disease (HD). Histologically, 27 NHL cases were intermediate grade (five cases) or high grade (22 cases, 14 of the small noncleaved cell type), according to the Working Formulation. Eight NHL cases, including four anaplastic large cell (ALC) BerH2 (CD30)-positive lymphomas, were in the miscellaneous group. Immunohistologic and/or gene rearrangement analysis showed the B-cell origin of 20 of the 24 NHL cases studied. At presentation, 71% of NHL patients had advanced stages (Stage III or IV), and 85% had extranodal disease (predominantly gastrointestinal tract and marrow). Of the 23 patients evaluable for treatment, only seven had a complete clinical response after lymphoma therapy; the median survival of 34 evaluable patients was 22 months after the diagnosis of NHL. Fifteen patients died; most deaths were attributable to progressive lymphoma and opportunistic infections. As with NHL, advanced disease, extranodal involvement, aggressive histologic findings, and poor response to therapy were also observed in patients with HD. This study shows that lymphoid neoplasias occurring in Italian IVDU with HIV infection and those previously reported in North American homosexual men with HIV infection share similar clinicopathologic features. However, some features such as the absence of history of Kaposi's sarcoma at diagnosis, the lack of detection of primary brain and rectal NHL, and the occurrence of B-cell ALC BerH2 (CD30)-positive NHL were observed uniquely in this series of patients.