This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simonelli, C. Articles by Tirelli, U. Search for Related Content PubMed PubMed Citation Articles by Simonelli, C. Articles by Tirelli, U. Social Bookmarking                            What's this?

Clinical Features and Outcome of Primary Effusion Lymphoma in HIV-Infected Patients: A Single-Institution Study

Cecilia Simonelli, Michele Spina, Roberta Cinelli, Renato Talamini, Rosamaria Tedeschi, Annunziata Gloghini, Emanuela Vaccher, Antonino Carbone, Umberto Tirelli

From the Divisions of Medical Oncology A and Pathology, and Epidemiology and Microbiology Units, National Cancer Institute, Aviano, Italy.

Address reprint requests to Umberto Tirelli, MD, Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano (PN), Italy; e-mail: omaoffice{at}cro.it.

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
Purpose: To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkin’s lymphomas (NHLs).

Patients and Methods: From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75).

Results: Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups).

Conclusion: PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
PRIMARY EFFUSION lymphoma (PEL) is a peculiar clinicopathologic entity characterized by human herpesvirus 8 (HHV-8) infection of tumor clone and by a peculiar tropism of the serous body cavities.^1,2 HHV-8 occurs in 100% of patients and is frequently, although not always, associated with Epstein-Barr virus infection.^3–7 At the clinicopathologic level, PEL is characterized by growth in the liquid phase in the absence of detectable tumor masses spreading along serous membranes without infiltrative growth patterns. Extraserous involvement of PEL has been reported. Some cases of PEL extend into tissues underlying the serous cavities, including the omentum and the lymph nodes, mediastinum, and lung.^1,2,5,6,8 Moreover, some cases of extracavitary nodal presentation with a subsequent development of effusion have been reported.⁵ PEL usually displays a non-B or non-T phenotype, but immunogenotypic studies have defined its B-cell origin. Morphologically, PEL bridges immunoblastic anaplastic features and displays a certain degree of plasma-cell differentiation as shown by immunoglobulin positivity for CD138/syndecan-1, a plasma cell–specific antigen.^1,6,7,9–12 The differential diagnosis of PEL from other non-Hodgkin’s lymphomas (NHLs) involving body cavities is not feasible on pure clinical and morphologic grounds, but it is enhanced by biologic characteristics, such as positivity for HHV-8 sequences on biopsies.^13,14

PEL is a rare subset of large B-cell lymphoma that mainly occurs in AIDS patients and less frequently occurs in other groups, including elderly patients and organ transplantation recipients.^13,15–19 HIV patients affected by PEL usually have advanced AIDS, and they have been described as poor candidates for aggressive chemotherapy (CT).¹⁰ In previous multi-institutional clinical series, the median survival time has been reported to be no longer than 3 months.^5,10

The aim of our study was to describe the clinical features and outcome of HIV-associated PEL diagnosed and treated in our institution from April 1987 to June 2002. Moreover, we compared the clinical characteristics and outcome of HIV-associated PEL with those of the other HIV-associated NHLs diagnosed and treated during the same period in our institution.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
The PEL relative incidence was calculated from the overall number of patients with HIV infection who had systemic NHL that was diagnosed and treated at the Aviano Cancer Center (Aviano, Italy) from April 1987 to June 2002. The clinical features and the outcome of 11 PEL patients were compared with 162 patients affected by the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). Seventy-four cases of Burkitt’s and Burkitt’s-like lymphomas were not included in the analysis. PEL patients are different from patients with Burkitt’s lymphomas because of clinical presentation and phenotypic and molecular genetics characteristics.² Moreover, our group has recently reported the clinical characteristics and response to therapy of our series of patients with Burkitt’s lymphoma associated to HIV infection.²⁰ Thirty patients with other histologic subtypes, according to 2001 WHO tumor classification,²¹ were excluded from the analysis.

Diagnosis
PEL diagnosis was achieved as follows. Samples of lymphomatous effusions were collected under sterile conditions during diagnostic procedures after centrifugation, and the effusion sediments were used to prepare smears and cell blocks. For morphologic studies, cytospin smears were routinely fixed and stained by Papanicolaou method for cell-block preparations²²; cell pellets were Bouin fixed and treated according to a standard regimen used at the Division of Pathology in Aviano. The sectioned material from cell blocks was stained with hematoxylin and eosin. In all cases, the smears and cell blocks showed a tumor cell population of 95% or greater, as evaluated by morphologic and immunophenotypic analysis.

In all samples, the immunophenotypic and immunogenotypic characterization was also performed, as well as the determination of tumor infection by Epstein-Barr virus and HHV-8 according to previously reported methods.^3,6,23 All NHL cases were reviewed (A.G. and A.C.) for the purpose of this study and were classified according to the 2001 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues.²¹

Staging
At diagnosis, all patients were evaluated for extent of HIV disease and NHL by physical examination, including height and weight, performance status according to the Eastern Cooperative Oncology Groups scale (0 to 4), measurement of all involved palpable lesions, complete blood cell count, blood chemistry, chest radiography, computed tomography of the thorax and abdomen, bone marrow aspiration and biopsy, lumbar puncture for spinal fluid, ECG and left ventricular ejection fraction evaluation, and CD4 cell count. HIV viral load was measured only in patients diagnosed and treated after January 1997. Stages for lymphomas were assigned according to the Ann Arbor classification of disease stages.²⁴ The revised classification system for HIV infection by the Centers for Disease Control was used for the AIDS diagnosis; according to WHO, only Centers for Disease Control clinical criteria were adopted.²⁵

Treatment
Patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimens every time the clinical conditions allowed chemotherapeutic treatment according to phase II and III therapeutic protocol running in our institution at that time. Since June 1998, NHL CD20-positive patients were treated with rituximab plus infusional cyclophosphamide, etoposide, and doxorubicin.²⁶

Highly active antiretroviral therapy (HAART) was introduced in our institution at the beginning of 1997; since then, patients with HIV-related NHL were treated with CT and concomitant HAART every time the clinical conditions and CT-related toxicity allowed it, irrespective of CD4 count and HIV viral load. Antiretroviral regimens were selected based on patient prior therapy, usually two reverse transcriptase inhibitors plus one protease inhibitor or one nonnucleoside reverse transcriptase inhibitor.

Response Evaluation
Complete remission was defined as the complete absence of clinically detectable tumors and normalization of previously abnormal radiographic findings persisting for at least 4 weeks. Partial remission was defined as the reduction of at least 50% in the product of the perpendicular diameters of all tumors assessed by physical examination or radiographic check-up persisting for more than 1 month with no new lesions occurring. Stable disease was described as a lower than 25% change in the product of the perpendicular diameters of all tumors. Progressive disease was defined as a higher than 25% increase in the measured lesions or the occurrence of new lesions.

Statistical Methods
Significant tests for proportions were computed by Fisher’s exact test, and differences between quantitative parameters were determined by the Wilcoxon rank sum test. Results were considered to be statistically significant when P .05 (two-sided).²⁷ Survival duration was calculated from the date of CT initiation to death or to the last known examination; only the treated patients were included. Survival curves were estimated by the Kaplan-Meier method, and differences between subgroups were assessed using the log-rank test.²⁸

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
Patients
From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated at the Aviano Cancer Center. PEL was diagnosed in 11 patients (4%), PBLOC was diagnosed in 11 patients (4%), and diffuse large B-cell lymphoma were diagnosed in 151 patients (54.5%), who were divided into two subtypes and morphologic variants (IBL, n = 76, 27.4%; CBCL, n = 75, 27%). Burkitt’s and Burkitt’s-like lymphomas were identified in 74 patients (26.8%), whereas in 30 patients (11%), the diagnosed lymphoma belonged to other histologic subtypes according to 2001 WHO tumor classification.²¹

Clinical Characteristics and Outcome of PEL
The epidemiologic characteristics and the clinical features of the 11 PEL patients are listed in Table 1. Briefly, 10 of 11 patients were male; seven of 11 patients reported homosexual intercourse as a risk factor for HIV infection; seven of 11 patients were diagnosed with full-blown AIDS at the time of PEL onset; and four of 11 patients had another HHV-8–associated disease (Kaposi’s sarcoma, n = 3; Castleman disease, n = 1).

At the onset of the lymphoma disease, mean values of CD4 count were equal to 98/µL. HIV viremia was available only in patients diagnosed after 1997 (five of 11 patients), and its mean value was 41,662 copies/mL (Table 2).

Eight of 11 patients were treated with CHOP-like regimens. After 1997, when the protease inhibitors became available in Italy, patients were treated with CHOP-like regimens plus HAART (five of eight CT-treated patients). One patient was treated with HAART alone, and two patients were not treated with CT (one patient because, as mentioned above, the diagnosis was made postmortem and one because the clinical condition did not allow any aggressive approach, Table 3).

The demographic data and HIV infection characteristics at the onset of NHL of the PEL patients and of the others three groups of NHL patients are listed in Table 2. We observed the following statistically significant differences between the groups: in regard to the distribution of risk factors for HIV infection, the PEL group had a statistically significant higher percentage of homosexual men compared with the CBCL group (54% v 17%, respectively; P = .009); and the PEL group had a statistically significant higher percentage of patients (64%) with a diagnosis of full-blown AIDS at the onset of lymphoma compared with all three groups of patients (Table 2).

At baseline, the mean value of the CD4 count was higher in patients affected by the other three groups of NHL compared with patients affected by PEL (mean CD4 count: 163/µL in the PBLOC group, 133/µL in the IBL group, and 200/µL in the CBCL group; Table 2). As with PEL patients, the HIV viremia was available only in patients diagnosed after 1997 (mean: 125,232 copies/mL in the PBLOC group, 57,867 copies/mL in the IBL group, and 80,399 copies/mL in the CBCL group; Table 2).

At the onset of lymphoma, we investigated the following clinical features of the neoplastic disease: performance status, stage according to Ann Arbor system, systemic symptoms, International Prognostic Index, and lactate dehydrogenase levels above the normal range. No significant differences were observed between the groups regarding these features except for stage (Table 5).

View larger version (12K): [in this window] [in a new window]   Fig. 1. Survival by histology: (——), primary effusion lymphoma (n = 9); (— - —), plasmoblastic lymphoma of oral cavity (n = 11); (- - - -), immunoblastic lymphoma (n = 68); (. . . . .), centroblastic B-cell lymphoma (n = 69).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
NHL is still one of the major causes of morbidity and mortality in HIV-infected patients.²⁹ It has been extensively reported that the majority of AIDS-related NHLs are diffuse B-cell lymphomas of the following types: small noncleaved-cell lymphomas, Burkitt’s and non-Burkitt’s lymphomas (40%), large-cell lymphomas (30%), and large-cell immunoblastic plasmacytoid lymphomas (30%). It is well known that PEL is a less common type of NHL.^1,5,10,30,31 In our institution, from April 1987 to June 2002, we diagnosed and treated 277 patients with AIDS-related NHL belonging to the following histologic types: PEL, n = 11 (4%); PBLOC, n = 11 (4%); IBL, n = 76 (27.4%); CBCL, n = 75 (27%); Burkitt’s and Burkitt’s-like lymphomas, n = 74 (26.8%); and other histologic types, n = 30 (11%).

Our series confirmed the previous reported PEL incidence (4% in HIV-infected patients).^2,32 But the incidence seems to be much higher than the incidence (0.13%) reported by a recent United States population-based AIDS and cancer registry study focused on the identification of AIDS-associated NHL in serous body cavity sites as a surrogate for PEL.³³ Of course, the discrepancy between the two incidences might be a result of the different methodologic characteristics of the studies. The principal limitation of the United States study was its reliance on registry data; the lack of a morphology code for PEL and inaccuracies in the coding of lymphoma site could have led them to miss some cases of PEL. Moreover, the registry reported only primary sites, and the authors did not include pericardial lymphomas. However, we can not completely rule out the hypothesis that the different incidences in PEL between United States and Italy might be the result of a different distribution of HHV-8 infection.³⁴ Moreover, in the United States, HAART was introduced into clinical practice earlier than in Italy; therefore, we can not exclude the possibility that the earlier use of HAART could have affected PEL distribution in the United States HIV population because PEL is so strictly related to immune depletion. We analyzed the PEL incidence according to the date of HAART introduction in our institution, and we observed a slight increase in the PEL incidence in the post-HAART era. In fact, we observed five cases of PEL (3.1%) of 161 overall NHLs diagnosed pre-HAART and six cases of PEL (5.2%) of 115 overall NHLs diagnosed post-HAART. However, it is of note that, in the post-HAART era, none of the patients were receiving HAART for longer than 4 weeks before PEL onset (data not shown).

In regard to the clinical characteristics of PEL, our data confirmed the data reported in other multi-institutional series.^1,5,10 In fact, PEL occurred mainly in homosexual men (63%) and in the late stage of HIV infection; 64% of the patients had a full-blown AIDS diagnosis, and this percentage was statistically significantly higher than the percentages observed in the other three subgroups of HIV patients affected by other NHLs (Table 2). Immunodepletion seemed to be much more important in the PEL group (mean CD4 cell count, 98/µL) compared with HIV patients affected by one of the other three groups of NHL, even if no statistically significant differences were observed. We believe that the statistical significance could have been missed because of the small size of the PEL group. At the onset of PEL, four (36.6%) of 11 patients had another HHV-8–associated disease (Kaposi’s sarcoma, n = 3; and Castleman disease, n = 1); whereas five (45%) of 11 patients had visceral involvement. When we compared the clinical characteristics of the lymphoma at the onset of the disease, no statistically significant differences regarding systemic symptoms, International Prognostic Index, and lactate dehydrogenase levels above the normal range were seen between PEL and the other three groups of NHL (Table 5). However, regarding the distribution of lymphoma stage, we found a statistically significant difference between PEL patients and the other HIV patients affected by other NHLs, but PEL disease is classified as stage IV by definition.

As previously reported,⁸ at diagnosis, six patients were evaluated using conventional computed tomography scans of the chest and abdomen. In all patients, computed tomography scan confirmed chest x-ray findings (unilateral or bilateral effusion in the absence of parenchymal opacities or mediastinal enlargement); but in addition, in all six patients, computed tomography revealed a slight thickening of the parietal pleural, and it showed a pericardial thickening in four patients.

Eight of 11 patients were treated with CHOP-like regimens, whereas one of 11 patients was treated with HAART alone. Three patients reached complete response, and the median overall survival time was 6 months, longer than the one observed in previous PEL AIDS-related series.^1,5,10 It is of note that two of three patients (patients 6 and 10, Table 3) with complete responses were treated with CT and HAART; these patients showed a long survival too (30 and 35 months, respectively). Moreover, one patient treated with HAART alone achieved a complete response, and she is still alive without any relapse. This is not the only observation reporting complete response in AIDS-related PEL treated without antiblastic drugs. In two case reports, Oksenhendler et al³⁵ and Hocqueloux et al³⁶ observed two complete remissions in two patients affected by AIDS-related PEL; one patient was treated with two reverse transcriptase inhibitors, and the other patient was treated with HAART plus cidofovir plus interferon alpha. The mechanism through which HAART might control PEL progression is not clear. Because of the extremely low incidence of PEL, little information is available about the effect of HAART on HHV-8 viral load in the peripheral blood or in the effusion.^37,38 We studied the HHV-8 viral load in the effusions of two of our patients during the few weeks of HAART before CT. We observed a transient decrease of HHV-8 viral load in the pleural effusion of one of the two patients.³⁷ In five of 11 patients diagnosed after 1997, plasma samples were available to measure HHV-8 plasma viremia; in all five patients, HHV-8 plasma viremia was detectable before starting specific therapy (CT or HAART, data not shown).³⁸

PEL patients (patients 1 to 5, Table 3) diagnosed and treated before the introduction of HAART in clinical practice (1997) showed a poor response to CT and a worse outcome (survival time range, 0.5 to 4.5 months; Table 3). HAART is able to improve the prognosis of AIDS-related lymphomas,^39–42 and our experience and the experiences of Oksenhendler et al³⁵ and Hocqueloux et al³⁶ are the first clinical evidences for the potential benefit of HAART in the treatment of PEL.

PEL showed a statistically significant worse outcome compared with the CBCL group (overall survival at 2 years, 33% v 53%, respectively; P = .0002; Fig 1); however, no significant differences regarding overall survival were seen between the PEL, PBLOC, and IBL groups (Figs 1). Even if no statistically significant differences in the overall survival were observed between the PEL and the PBLOC group, from a the clinical point of view, we can affirm that the PBLOC group seems to have a better prognosis than PEL, one more similar to the CBCL group. In fact, no significant differences were noticed between the overall survivals of the PBLOC and CBCL groups (data not shown). However, the IBL group seems to have a poor clinical outcome, which is similar to the PEL group; and in fact, the IBL group has a significantly worse outcome when compared with the CBCL group (data not shown). It is important to point out that all patients included in the analysis were treated with CHOP-like regimens, and the percentages of patients treated during the HAART era were 63%, 54%, 36%, and 61% in the PEL, PBLOC, IBL, and CBCL groups, respectively. In addition, we would like to mention that we did not include in the analysis the Burkitt’s lymphoma group because the characteristics and the response to therapy of our institutional series of Burkitt’s lymphomas in the pre-HAART era have been reported elsewhere.²² In the pre-HAART era, the median overall survival time of our series of Burkitt’s lymphoma was 7 months, which was not significantly different from the overall survival time observed in the present series of PEL (6 months). The analysis of Burkitt’s lymphoma associated with HIV infection during the HAART era is still ongoing.

In conclusion, our single-institution study showed that PEL is a rare HIV NHL type that occurs as a late manifestation of HIV infection and has a poor clinical outcome and a shorter overall survival compared only with the CBCL group. However, there are some clinical evidences that, even in this rare NHL subtype, the introduction of HAART could improve the clinical outcome of PEL as it has for the other NHL subtypes.^39–43

	AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
The authors indicated no potential conflicts of interest.

	ACKNOWLEDGMENTS

 
We thank Daniela Furlan for her expert assistance in the revision and preparation of the manuscript.

	NOTES

 
Supported by grants from the Associazione Italiana per la Ricerca sul Cancro and Istituto Superiore Di Sanita.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS’ DISCLOSURES OF... REFERENCES

 
1. Nador RG, Cesarman E, Chadburn A, et al: Primary effusion lymphoma: A distinct clinicopathologic entity associated with the Kaposi’s sarcoma-associated herpes virus. Blood 88:645–656, 1996[Abstract/Free Full Text]

2. Carbone A, Gaidano G: HHV-8 positive body cavity-based lymphoma: A novel lymphoma entity. Br J Haematol 97:515–522, 1997[CrossRef][Medline]

3. Chang Y, Cesarman E, Pessin MS, et al: Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865–1869, 1994[Abstract/Free Full Text]

4. Fassone L, Bhatia K, Gutierrez M, et al: Molecular profile of Epstein-Barr virus infection in HHV-8-positive primary effusion lymphoma. Leukemia 14:271–277, 2000[CrossRef][Medline]

5. Cesarman E, Chang Y, Moore PS, et al: Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body cavity-based lymphomas. N Engl J Med 332:1186–1191, 1995[Abstract/Free Full Text]

6. Carbone A, Gloghini A, Vaccher E, et al: Kaposi’s sarcoma-associated herpesvirus DNA sequences in AIDS-related and AIDS-unrelated lymphomatous effusions. Br J Haematol 94:533–543, 1996[CrossRef][Medline]

7. Jaffe ES: Primary body-cavity-based AIDS-related lymphomas: Evolution of a new disease entity. Am J Clin Pathol 105:141–143, 1996[Medline]

8. Morassut S, Vaccher E, Balesteri L, et al: HIV-associated HHV-8 positive primary lymphomatous effusions: Radiological findings in six patients. Radiology 205:459–463, 1997[Abstract/Free Full Text]

9. Said JW, Tasaka T, Takeuchi S, et al: Primary effusion lymphoma in women: report of two cases of Kaposi’s sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women. Blood 88:3124–3128, 1996[Abstract/Free Full Text]

10. Ansari MQ, Dawson DB, Nador R, et al: Primary body cavity-based AIDS-related lymphomas. Am J Clin Pathol 105:221–229, 1996[Medline]

11. Gaidano G, Gloghini A, Gattei V, et al: Association of KSHV positive primary effusion lymphoma with expression of the CD138/syndecan-1 antigen. Blood 90:4894–4900, 1997[Abstract/Free Full Text]

12. Capello D, Gaidano G, Gallicchio M, et al: The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma. Leukemia 14:285–291, 2000[CrossRef][Medline]

13. Cesarman E, Nador RG, Aozasa K, et al: Kaposi’s sarcoma-associated herpesvirus in non-AIDS related lymphomas occurring in the body cavities. Am J Pathol 149:53–57, 1996[Abstract]

14. Said JW, Chien K, Tasaka T, et al: Kaposi’s sarcoma associated herpesvirus (KSHV or HHV8) in primary effusion lymphomas: Ultrastructural demonstration of herpesvirus in lymphoma cell lines. Blood 87:4937–4943, 1996[Abstract/Free Full Text]

15. Gaidano G, Pastore C, Gloghini A, et al: Distribution of human hepersvirus-8 sequences throughout the spectrum of AIDS-related neoplasia. AIDS 10:941–949, 1996[Medline]

16. Okada T, Katano H, Tsutsumi H, et al: Body-cavity-based lymphoma in an elderly AIDS-unrelated male. Int J Hematol 67:417–422, 1998[CrossRef][Medline]

17. Ascoli V, Scalzo CC, Danese C, et al: Human herpes virus-8 associated primary effusion lymphoma of the pleural cavity in HIV-negative elderly men. Eur Respir J 14:1231–1234, 1999[Abstract]

18. Klepfish A, Sarid R, Shtalrid M, et al: Primary effusion lymphoma (PEL) in HIV-negative patients: A distinct clinical entity. Leuk Lymphoma 41:439–443, 2001[Medline]

19. Kapelushnik J, Ariad S, Benharroch D, et al: Post renal transplantation human herpes virus 8-associated lymphoproliferative disorder and Kaposi’s sarcoma. Br J Haematol 113:425–428, 2001[CrossRef][Medline]

20. Spina M, Tirelli U, Zagonel V, et al: Burkitt’s lymphoma in adults with and without human immunodeficiency virus infection: A single-institution clinicopathologic study of 75 patients. Cancer 82:766–774, 1998[CrossRef][Medline]

21. Jaffe ES, Harris NL, Stein H, et al (eds): Pathology and genetics of tumours of haematopoietic and lymphoid tissues, in World Health Organization Classification of Tumours. Lyon, France, International Agency for Research on Cancer Press, 2001

22. Naylor B: Pleural, peritoneal and pericardial fluids, in Bibbo M (ed): Comprehensive Cytopathology. Philadelphia, PA, Saunders, 1991, pp 541–560

23. Carbone A, Cilia AM, Gloghini A, et al: Establishment of HHV-8 positive and HHV8-negative lymphoma cell lines from primary lymphomatous effusions. Br J Haematol 102:1081–1089, 1998[CrossRef][Medline]

24. Carbone PP, Kaplan HS, Musshoff K, et al: Report of the committee on non-Hodgkin’s disease classification. Cancer Res 31:1860–1861, 1971[Free Full Text]

25. Ancelle-Park R: Expanded European AIDS case definition. Lancet 341:441, 1993[Medline]

26. Spina M, Sparano JA, Jaeger U, et al: Rituximab and chemotherapy is highly effective in patients with CD20-positive non-Hodgkin’s lymphoma and HIV infection. AIDS 17:137–138, 2002

27. Snedecor GW, Cochran WG: Statistical Methods. Ames, IA, Iowa State University Press, 1980

28. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481, 1958[CrossRef]

29. Jacobson LP, Yamashita TE, Detels R, et al: Impact of potent antiretroviral therapy on the incidence of Kaposi’s sarcoma among HIV-1-infected individuals. J Acquir Immune Defic Syndr Hum Retrovirol 21:S34–S41, 1999 (suppl 1)

30. The Non-Hodgkin’s Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphoma: Summary and description of a working formulation for clinical usage. Cancer 49:2112–2135, 1982[CrossRef][Medline]

31. Knowles DM, Chamulak GA, Subar M, et al: Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS): The New York University Medical Center experience with 105 patients (1981–1986). Ann Intern Med 108:744–753, 1988[Abstract/Free Full Text]

32. Gaidano G, Carbone A: Primary effusion lymphoma: A liquid phase lymphoma of fluid-filled body cavities. Adv Cancer Res 80:115–146, 2001[Medline]

33. Mbulaiteye SM, Biggar RJ, Goedert JJ, et al: Pleural and peritoneal lymphoma among people with AIDS in the United States. J Acquir Immune Defic Syndr 29:418–421, 2002[Medline]

34. Tedeschi R, Dillner J, De Paoli P: Laboratory diagnosis of human herpesvirus 8 infection in humans. Eur J Clin Microbiol Infect Dis 21:831–844, 2002[Medline]

35. Oksenhendler E, Clauvel JP, Jouveshomme S, et al: Complete remission of a primary effusion lymphoma with antiretroviral therapy. Am J Hematol 57:266, 1998[Medline]

36. Hocqueloux L, Agbalika F, Oksenhendler E, et al: Long-term remission of an AIDS-related primary effusion lymphoma with antiviral therapy. AIDS 15:280–281, 2001[CrossRef][Medline]

37. Spina M, Gaidano G, Carbone A, et al: Highly active antiretroviral therapy in human herpesvirus-8-related body-cavity-based lymphoma. AIDS 12:955–956, 1998[Medline]

38. Tedeschi R, Bidoli E, Simonelli C, et al: KSHV viral load in peripheral blood of HIV+ patients with primary effusion lymphoma. Presented at Fifth International Workshop on Kaposi-Sarcoma-Associated Herpesvirus and Related Agents. Kloster Irsee, Germany, August 7–11, 2002 (abstr)

39. Thiessard F, Morlat P, Marimoutou C, et al: Prognostic factors after non-Hodgkin’s lymphoma in patients infected with the human immunodeficiency virus. Cancer 88:1696–1702, 2000[CrossRef][Medline]

40. Levine AM: Acquired immunodeficiency syndrome-related lymphoma: Clinical aspects. Semin Oncol 27:442–453, 2000[Medline]

41. Tam HK, Zhang ZF, Jacobson LP, et al: Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi’s sarcoma or non-Hodgkin lymphoma. Int J Cancer 98:916–922, 2002[CrossRef][Medline]

42. Gerard L, Galicier L, Maillard A, et al: Systemic non-Hodgkin’s lymphoma in HIV-infected patients with effective suppression of HIV-replication: Persistent occurrence but improved survival. J Acquir Immune Defic Syndr 30:478–484, 2002[Medline]

43. Antinori A, Cingolani A, Alba L, et al: Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS 15:1483–1491, 2001[CrossRef][Medline]

Submitted June 3, 2003; accepted August 11, 2003.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz HIV-associated lymphomas and gamma-herpesviruses Blood, February 5, 2009; 113(6): 1213 - 1224. [Abstract] [Full Text] [PDF]

				A. Cassoni, U. Ali, J. Cave, S. G. Edwards, A. Ramsay, R. F. Miller, and S. M. Lee Remission After Radiotherapy for a Patient With Chemotherapy-Refractory HIV-Associated Primary Effusion Lymphoma J. Clin. Oncol., November 10, 2008; 26(32): 5297 - 5299. [Full Text] [PDF]

				P. Gasperini, S. Sakakibara, and G. Tosato Contribution of viral and cellular cytokines to Kaposi's sarcoma-associated herpesvirus pathogenesis J. Leukoc. Biol., October 1, 2008; 84(4): 994 - 1000. [Abstract] [Full Text] [PDF]

				Y.-B. Chen, H. Yu, A. Gillani, and J. R. Brown AIDS-Associated Plasmablastic Lymphoma Presenting at the Insertion Site of a Peritoneal Dialysis Catheter J. Clin. Oncol., July 20, 2007; 25(21): 3176 - 3178. [Full Text] [PDF]

				D. A. Davis, K. E. Singer, I. P. Reynolds, M. Haque, and R. Yarchoan Hypoxia Enhances the Phosphorylation and Cytotoxicity of Ganciclovir and Zidovudine in Kaposi's Sarcoma-Associated Herpesvirus Infected Cells Cancer Res., July 15, 2007; 67(14): 7003 - 7010. [Abstract] [Full Text] [PDF]

				Y.-B. Chen, A. Rahemtullah, and E. Hochberg Primary Effusion Lymphoma Oncologist, May 1, 2007; 12(5): 569 - 576. [Abstract] [Full Text] [PDF]

				C. E. Petre, S.-H. Sin, and D. P. Dittmer Functional p53 Signaling in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas: Implications for Therapy J. Virol., February 15, 2007; 81(4): 1912 - 1922. [Abstract] [Full Text] [PDF]

				T. Halfdanarson, S. Markovic, U Kalokhe, and M Luppi A non-chemotherapy treatment of a primary effusion lymphoma: durable remission after intracavitary cidofovir in HIV negative PEL refractory to chemotherapy Ann. Onc., December 1, 2006; 17(12): 1849 - 1850. [Full Text] [PDF]

				H. Masur Management of Patients with HIV in the Intensive Care Unit. Proceedings of the ATS, January 1, 2006; 3(1): 96 - 102. [Abstract] [Full Text] [PDF]

				W. H. Navarro and L. D. Kaplan AIDS-related lymphoproliferative disease Blood, January 1, 2006; 107(1): 13 - 20. [Abstract] [Full Text] [PDF]

				C. Hoffmann, M. Tiemann, C. Schrader, D. Janssen, E. Wolf, M. Vierbuchen, R. Parwaresch, K. Ernestus, A. Plettenberg, A. Stoehr, et al. AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping Blood, September 1, 2005; 106(5): 1762 - 1769. [Abstract] [Full Text] [PDF]

				E. Boulanger, L. Gerard, J. Gabarre, J.-M. Molina, C. Rapp, J.-F. Abino, J. Cadranel, S. Chevret, and E. Oksenhendler Prognostic Factors and Outcome of Human Herpesvirus 8-Associated Primary Effusion Lymphoma in Patients With AIDS J. Clin. Oncol., July 1, 2005; 23(19): 4372 - 4380. [Abstract] [Full Text] [PDF]

				S. T. Lim and A. M. Levine Recent Advances in Acquired Immunodeficiency Syndrome (AIDS)-related Lymphoma CA Cancer J Clin, July 1, 2005; 55(4): 229 - 241. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simonelli, C. Articles by Tirelli, U. Search for Related Content PubMed PubMed Citation Articles by Simonelli, C. Articles by Tirelli, U. Social Bookmarking                            What's this?