Antiviral and immunomodulatory treatment for AIDS-related primary central nervous system lymphoma: AIDS Malignancies Consortium pilot study 019.
OBJECTIVE
A consistent association with Epstein-Barr Virus (EBV) distinguishes acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL) from that which occurs in the general population. Recent descriptions of long-term remissions in patients with posttransplantation EBV-associated PCNSL who received EBV-specific therapy suggest some antitumor effect is anti-EBV mediated.


METHODS
We enrolled 4 patients with AIDS-related PCNSL into a novel antiviral and immunomodulatory protocol. An additional patient was treated in a similar fashion off protocol. Treatment consisted of intravenously administered zidovudine (1.5 g twice daily), ganciclovir (5 mg/kg twice daily), and interleukin-2 (2,000,000 U twice daily). After 2 weeks of therapy, patients were switched to oral ganciclovir (1 g 3 times daily), patient-specific, highly active, antiretroviral therapy, and subcutaneous interleukin-2 (2,000,000 U 3 times weekly). A final patient was treated with intravenous zidovudine and hydroxyurea. All 6 patients had advanced-stage AIDS as reflected by a CD4+ T-lymphocyte cell count of < 50/microL and a detectable human immunodeficiency virus (HIV)-1 viral RNA load (median copies, 135,000/mL; range, 2170-360,000/mL). One of 4 protocol-enrolled patients remains in complete remission with > 4 years' follow-up.


RESULTS
Three patients died from complications of progressive PCNSL. Two patients treated off protocol exhibited favorable responses and remain in complete remission at 28 months and 52 months, respectively. Grade 3/4 myelosuppression was uniformly noted, but there were no clinically significant hemorrhagic or infectious complications.


CONCLUSIONS
We conclude that for patients with AIDS and PCNSL, treatments with dual efficacy against HIV and EBV merit further investigation. Our experience provides a platform for future studies.
Aboulafia
David M
DM
Divisions of Hematology and Oncology, Virginia Mason Medical Center and the University of Washington, Seattle, WA 9811, USA. hemdma@vmmc.org
Ratner
Lee
L
Miles
Steven A
SA
Harrington
William J
WJ
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007378:Interleukins / Q000627:therapeutic use*; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D007378:Interleukins