Treatment of AIDS-Related Primary Central Nervous System Lymphoma with Zidovudine, Ganciclovir, and Interleukin 2

Abstract

AIDS-related primary central nervous system lymphoma (AIDS PCNSL) is a rapidly fatal disease. Conventional therapeutic modalities offer little and new approaches are needed. Previous work has shown that zidovudine (AZT) in combination with other agents is active in retroviral lymphomas. Epstein-Barr virus (EBV) is detected in tumor tissue and cerebrospinal fluid of AIDS PCNSL patients. In a preliminary in vitro study we found that an Epstein-Barr virus-positive B cell line underwent apoptosis on coculture with AZT. This effect was accentuated by the addition of ganciclovir (GCV). We treated five patients with AIDS PCNSL with a regimen consisting of parenteral zidovudine (1.6 g twice daily), ganciclovir (5 mg/kg twice daily), and interleukin 2 (2 million units twice daily). Four of five had an excellent response. Two patients are alive and free of disease 22 and 13 months later; another responded on two separate occasions, 5 months apart, and the last patient responded with a 70-80% regression of tumor but could not be maintained on therapy owing to myelosuppression. We conclude that parenteral zidovudine, ganciclovir, and interleukin 2 is an active combination for AIDS-related central nervous system lymphoma.

Induction of a TRAIL mediated suicide program by interferon alpha in primary effusion lymphoma

“…It is interesting to note that like PEL cells, EBV+ cells were also killed by a thymidine analog (AZT) and not by other antiviral nucleosides and that this eect was also inhibited by thymidine. We have recently noted that high dose AZT has marked clinical activity in AIDS related EBV+ primary central nervous system lymphoma (Raez et al, 1999). We recently observed a marked clinical improvement in a PEL patient with lymphomatous meningitis treated with parenteral AZT and IFN-a after having failed conventional chemotherapy.…”

HIV‐associated plasmablastic lymphoma: Lessons learned from 112 published cases

“…EBV also seems to be strongly associated with HIV-associated PBL; our series reports the presence of EBV in 74% of published cases. Furthermore, early clinical studies showed promising results using EBV-directed therapy in patients with HIV-associated lymphomas with highdose zidovudine, interleukin 2, and ganciclovir [36,37]. Several investigators have challenged the association between PBL and HHV8.…”

Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8+ T-cell restoration

“…40 It is tempting to speculate that the presence of both gene products in PTLD might facilitate the selective targeting of actively replicating or reactivated EBV-positive B cells with combination antiviral therapy. 42,43 A more complete characterization of the coexpression of vTK and BGLF-4 gene products in PTLD is likely required before the use of multiple antiviral agents for prophylaxis and/or treatment of PTLD could be broadly advocated.…”