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Hodgkin’s disease inHIV-infected patients: report of eight cases usefully treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus granulocyte colony- stimulating factor

2002; Elsevier BV; Volume: 13; Issue: 7 Linguagem: Inglês

10.1093/annonc/mdf239

1569-8041

Roberto Gastaldi, P. Martino, Giuseppe Gentile, V. Picardi, M. S. De Propris, Maria Franca Pirillo, Annalisa De Vellis, Franco Mandelli,

Cytomegalovirus and herpesvirus research

In the era prior to active antiretroviral therapy (HAART) and in the absence of growth factors, the response rates of HIV-infected people with Hodgkin’s disease (HD-HIV) with standard chemotherapy ranged between 45% and 70%. Median survival was only in the approximate range of 8–18 months. The underlying complications of HIV infection and the unfavourable clinical and biological characteristics are the major factors affecting survival of these patients [1.Tirelli U. Vaccher E. Spina M. Carbone A. Hodgkin’s disease: clinical presentation and treatment.Cancer Treat Res. 2001; 104: 247-265Crossref PubMed Scopus (9) Google Scholar]. The use of granulocyte colony-stimulating factor (G-CSF) concomitantly with standard ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) but without antiretroviral therapy failed to improve results in HD-HIV patients, as reported by Levine et al. in a non-randomised, prospective, multi-institutional AIDS Clinical Trials Group (ACTG 149) study [2.Levine A.M. Li P. Cheung T. et al.Chemotherapy consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine with granulocyte-colony-stimulating factor in HIV-infected patients with newly diagnosed Hodgkin’s disease: a prospective, multi-institutional AIDS clinical trials group study (ACTG 149).J Acquir Immune Defic Syndr. 2000; 24: 444-450Crossref PubMed Scopus (83) Google Scholar]. Encouraging results in HD-HIV patients have recently been reported by Errante et al. with the EBVP (epirubicin, bleomycin, vinblastine, prednisone) regimen combined with G-CSF and nucleoside transcriptase inhibitor monotherapy [3.Errante D. Gabarre J. Ridolfo A.L. et al.Hodgkin’s disease in 35 patients with HIV infection: an experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF.Ann Oncol. 1999; 10: 189-195Abstract Full Text PDF PubMed Scopus (63) Google Scholar], and by Spina et al. witha weekly Stanford V regimen combined with HAART andG-CSF [4.Spina M. Gabarre J. Fasan M. et al.Stanford V regimen and concomitant highly active antiretroviral therapy is feasible and active in patients with Hodgkin’s disease and HIV infection.AIDS. 2000; 14: 1457-1458Crossref PubMed Scopus (7) Google Scholar]. In both studies, a high rate of complete remission (CR) was achieved (74% and 80%, respectively) with a low frequency of HIV-related complications; nevertheless, severe myelosuppression occurred in 32% and 90% of patients, and relapse rates were 38% and 25%, respectively [3.Errante D. Gabarre J. Ridolfo A.L. et al.Hodgkin’s disease in 35 patients with HIV infection: an experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF.Ann Oncol. 1999; 10: 189-195Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 4.Spina M. Gabarre J. Fasan M. et al.Stanford V regimen and concomitant highly active antiretroviral therapy is feasible and active in patients with Hodgkin’s disease and HIV infection.AIDS. 2000; 14: 1457-1458Crossref PubMed Scopus (7) Google Scholar]. We report here our experience in eight newly diagnosed HD-HIV outpatients (Table 1), consecutively treated between April 1994 and December 1999 at our haematology centre with standard ABVD [doxorubicin 25 mg/m2, bleomycin 10 mg/m2 (= 10 U/m2), vinblastine 6 mg/m2, dacarbazine 375 mg/m2, administered intravenously on days 1 and 15 for a maximum of six cycles; each cycle lasted 28 days]. G-CSF 5 µg/kg/day was administered subcutaneously from day 3 to day 12 and from day 17 to day 26 of each ABVD course. Pneumocystis carinii pneumonia and fungal prophylaxis were also administered during the ABVD regimen. The first six patients received ABVD + G-CSF without antiretroviral therapy, while the remaining two received HAART with stavudine plus lamivudine plus indinavir concomitantly to ABVD. A total of 44.5 ABVD regimens were administered (median 6 per patient; range 3.5–6). One patient received the first cycle of ABVD without G-CSF, and severe neutropenia with an absolute neutrophil count (ANC) of <500 cells/mm3 was observed on days 7 and 21 following ABVD administration. The median time over which G-CSF was administered in the remaining 43.5 ABVD courses was 9.5 days (range 7–10 days). Severe toxicity, with ANC <500 cells/mm3 and platelet count <25000/mm3, was observed at day 6 of the first course of ABVD plus G-CSF in one patient [one episode per 43.5 courses (2.3%)], while ANC 500–1000 cells/mm3 was found in two patients [two episodes per 43.5 courses (4.6%)], and anaemia with haemoglobin 6.5–7.5 g/dl was observed in two cases with bone marrow HD-HIV involvement [three episodes per 43.5 courses (6.9%)]. No delay or reduction in drugs was necessary. Two patients who were intravenous drug users discontinued ABVD, one after five and the other after four courses for acute hepatitis virus B. One patient developed pneumonic tuberculosis [one out of eight (12.5% of cases)]. At the end of chemotherapy, compared with baseline, the absolute mean CD4 decreased (163.3 and 269.7 cell/mm3, respectively) and the mean HIV.1 RNA remained at high level (152828 ± 127157 and 125833 ± 87458 copies/ml, respectively) in six patients who received ABVD without antiretroviral therapy, and in one of them an AIDS-related opportunistic infection was observed. On the other hand, no complication occurred in two patients treated with ABVD + G-CSF + HAART; a high level of viral load was shown at baseline in both patients (88000 and 270000 copies/ml) and both achieved an undetectable viral load at the end of the ABVD regimen. At the same time, the absolute number of CD4 cells/mm3 remained stable in one patient (459 and 459 cells/mm3, respectively) while it in-creased in the other (28 and 663 cells/mm3, respectively).Table 1Baseline features and outcome of ABVD plus G-CSF-treated HIV-infected patients with Hodgkin’s diseaseCharacteristicsTotal%RangeNumber of patients8Gender ratio (male:female)5:3Median age (years)2924–39HIV transmission routeIntravenous drug use450.0Sexually450.0Median CD4 (cells/mm3 ± SD)259 ± 19328–486CD4 <100 cells/mm3337.5CD4 <200 cells/mm3337.5Mean plasma HIV.1 RNA load (copies/ml ± SD)139000 ± 9194458000–280000CDC-HIV categories prior to lymphomaAsymptomatic (A)0–Symptomatic not AIDS (B)787.5AIDS (C)112.5Antiretroviral therapy prior to lymphoma675.0Systemic ‘B’ symptoms:787.5Fever + night sweats + weight loss229.0Fever + night sweats114.0Weight loss + fever/or night sweats0–Night sweats0–Fever457.0Karnofsky performance score (median)8050–100Ann Arbor clinical stageI0–II225.0III112.5IV5aVisceral plus lymph nodes = 1; lung plus lymph nodes plus spleen = 1; bone marrow plus hepar plus lymph nodes = 1; bone marrow plus lymph nodes = 1; bone marrow = 1.62.5Bone marrow involvement337.5Hodgkin’s disease histologyLymphocyte prevalence0–Nodular sclerosis225.0Mixed cellularity675.0Nadir of haematological parameters during ABVDHaemoglobin (g/dl ± SD)10.7 ± 1.67.1–14.5ANC (cells/mm3 ± SD)4450 ± 400510–17720Platelet count (cells/mm3 ± SD)183000 ± 7361220900–406000Complete response8100Relapse0–Death1bOne patient out of eight had a complete response.12.5Causes of deathLymphoma0Infection0Others1ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; G-CSF, granulocyte colony-stimulating factor; SD, standard deviation; CDC, revised Center of Disease Control Criteria of HIV infection, 1993; ANC, absolute neutrophil count.a Visceral plus lymph nodes = 1; lung plus lymph nodes plus spleen = 1; bone marrow plus hepar plus lymph nodes = 1; bone marrow plus lymph nodes = 1; bone marrow = 1.b One patient out of eight had a complete response. Open table in a new tab ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; G-CSF, granulocyte colony-stimulating factor; SD, standard deviation; CDC, revised Center of Disease Control Criteria of HIV infection, 1993; ANC, absolute neutrophil count. CR was achieved in all cases and no lymphoma relapses occurred after a median CR duration of 43 months (range 22–90 months). The median overall survival (OS) was 43.5 months (range 31–96 months). Of eight patients, one died in continuous complete response (CCR) 46 months after HD-HIV diagnosis, and 2 months after treatment with stavudine + lamivudine + ritonavir for acquired demyelinating polyradiculoneuropathy. Currently, seven patients are alive in CCR at 31, 36, 37, 48, 56, 58 and 96 months from HD-HIV diagnosis. Of these, six have been on HAART for a median time of 35 months (range 23–41 months), while the remaining patient was not treated because of cirrhosis decompensation. In our experience, the standard ABVD regimen is very well tolerated in HD-HIV out-patients with relatively well preserved immune function, inducing a high response rate and a long survival; the use of G-CSF is useful to prevent haematological toxicity, and no delay or reduction of drugs was shown. Nevertheless, HAART administration during or at the end of chemotherapy could contribute to long patient survival [5.Little R.F. Yarchoan R. Wilson W.H. Systemic chemotherapy for HIV-associated lymphoma in the era of highly active antiretroviral therapy.Curr Opin Oncol. 2000; 12: 438-444Crossref PubMed Scopus (22) Google Scholar]. The authors would like to thank Silvana Bedini for English revision of the manuscript. This work was supported by an AIDS National Project grant from the Istituto Superiore di Sanità.