A clinical, molecular and cytogenetic study of 12 cases of human herpesvirus 8 associated primary effusion lymphoma in HIV-infected patients.
BACKGROUND
Primary effusion lymphoma is a rare type of B-cell lymphoproliferative disorder which is mainly observed in patients with HIV infection. Lymphomatous cells bridge features of immunoblastic and anaplastic cells with a non-B non-T phenotype and are characterized by the presence of the human herpesvirus 8 genome. We report on the retrospective analysis of 12 cases.


METHODS
: Twelve HIV-infected patients with serous effusions containing large HHV8(+) lymphomatous cells were extensively evaluated to disclose associated visceral involvement. Clonality was assessed by IgH gene rearrangement PCR analysis (n = 11) or Southern blot (n = 1). EBV and HHV8 DNA sequences were detected by PCR analysis. Cytogenetics studies were performed in seven cases using RHG-banding.


RESULTS
Extraserous localizations of lymphoma were present in six cases (50%): mediastinal (n = 2), mesenteric (n = 2), pancreatic (n = 1), and bone marrow involvement (n = 1). A monoclonal rearrangement of IgH genes was demonstrated in six cases, an oligoclonal pattern in one, whereas no clonality could be detected in five. High HHV8 copy numbers were demonstrated in all effusion fluids, with EBV-co-infection in all cases but one. Cytogenetic analysis displayed a complex karyotype in all cases without recurrent abnormalities. Eight patients have died. Three patients are in complete remission at 28, 53 and 55 months after high-dose chemotherapy (n = 1), cidofovir and alpha-interferon combination therapy (n = 1), and antiretroviral therapy alone (n = 1).


CONCLUSIONS
The clinical and molecular pattern, as well as the response to therapy suggest that primary effusion lymphoma represents an heterogenous type of virus-induced B-cell lymphoproliferative disorder, sharing pathophysiological features with that induced by the Epstein-Barr virus and occurring in immunocompromised patients.
Boulanger
E
E
Department of Clinical Immunohematology, Hôpital Saint-Louis, Paris, France.
Agbalika
F
F
Maarek
O
O
Daniel
M T
MT
Grollet
L
L
Molina
J M
JM
Sigaux
F
F
Oksenhendler
E
E
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D002869:Chromosome Aberrations; D000077404:Cidofovir; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use; D007621:Karyotyping; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000821:virology*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000821:virology*; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000821:virology*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D014750:Vincristine / Q000627:therapeutic use; D014751:Vindesine / Q000008:administration & dosage; D019562:Viral Load
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D016898:Interferon-alpha; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003596:Cytosine; D003520:Cyclophosphamide; D000077404:Cidofovir; D014751:Vindesine; D011241:Prednisone; D008727:Methotrexate