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

R. Gastaldi*,1, P. Martino1, G. Gentile1, V. Picardi1, M. S. De Propris1, M. F. Pirillo2, A. De Vellis1 and F. Mandelli1

1 Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, University ‘La Sapienza’ of Rome, Via Benevento 6, 00161 Rome; 2 Virology, Istituto Superiore di Sanità of Rome, Italy (E-mail: gastaldi@bce.med.uniroma1.it)

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]. 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]. 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], and by Spina et al. with a weekly Stanford V regimen combined with HAART and G-CSF [4]. 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, 4].

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 <25 000/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 (152 828 ± 127 157 and 125 833 ± 87 458 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 (88 000 and 270 000 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).


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Table 1.  Baseline features and outcome of ABVD plus G-CSF-treated HIV-infected patients with Hodgkin’s disease
 
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].

Acknowledgements

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.

R. Gastaldi1*, P. Martino1, G. Gentile1, V. Picardi1, M. S. De Propris1, M. F. Pirillo2, A. De Vellis1 & F. Mandelli1

1Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, University ‘La Sapienza’ of Rome, Via Benevento 6, 00161 Rome; 2Virology, Istituto Superiore di Sanità of Rome, Italy (E-mail: gastaldi@bce.med.uniroma1.it)

References

1. Tirelli U, Vaccher E, Spina M, Carbone A. Hodgkin’s disease: clinical presentation and treatment. Cancer Treat Res 2001; 104: 247–265.[Medline]

2. Levine AM, 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: 444–450.[ISI][Medline]

3. Errante D, Gabarre J, Ridolfo AL 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: 189–195.[Abstract]

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: 1457–1458.[ISI][Medline]

5. Little RF, Yarchoan R, Wilson WH. Systemic chemotherapy for HIV-associated lymphoma in the era of highly active antiretroviral therapy. Curr Opin Oncol 2000; 12: 438–444. [ISI][Medline]





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