Long-term survival in AIDS-related primary central nervous system lymphoma

Neel K Gupta; Amber Nolan; Antonio Omuro; Erin G Reid; Chia-Ching Wang; Gabriel Mannis; Michael Jaglal; Julio C Chavez; Paul G Rubinstein; Ann Griffin; Donald I Abrams; Jimmy Hwang; Lawrence D Kaplan; Judith A Luce; Paul Volberding; Patrick A Treseler; James L Rubenstein

doi:10.1093/neuonc/now155

Long-term survival in AIDS-related primary central nervous system lymphoma

Neuro Oncol. 2017 Jan;19(1):99-108. doi: 10.1093/neuonc/now155. Epub 2016 Aug 30.

Authors

Neel K Gupta¹, Amber Nolan¹, Antonio Omuro¹, Erin G Reid¹, Chia-Ching Wang¹, Gabriel Mannis¹, Michael Jaglal¹, Julio C Chavez¹, Paul G Rubinstein¹, Ann Griffin¹, Donald I Abrams¹, Jimmy Hwang¹, Lawrence D Kaplan¹, Judith A Luce¹, Paul Volberding¹, Patrick A Treseler¹, James L Rubenstein²

Affiliations

¹ Division of Hematology/Oncology, University of California, San Francisco (N.K.G., C.W., G.M., D.I.A., L.D.K., J.A.L., P.V., J.L.R.); Department of Pathology, University of California, San Francisco (A.N., P.A.T.); Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (A.O.); Division of Hematology/Oncology, University of California, San Diego (E.G.R.); Division of Hematology/Oncology, San Francisco General Hospital (C.W., D.I.A., J.A.L.); Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL (M.J., J.C.C.); Department of Medicine, Section of Hematology/Oncology, John H. Stroger Jr. Hospital of Cook County, Ruth M. Rothstein CORE Center, Developmental Center for AIDS Research, Chicago, IL (P.G.R.); Department of Internal Medicine, Rush University Medical Center, Chicago, IL (P.G.R.); UCSF Cancer Registry, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (A.G.); Helen Diller Family Comprehensive Cancer Center, University of California San Francisco (D.I.A., J.H., L.D.K., J.A.L., P.V., P.A.T., J.L.R.); Biostatistics and Computational Biology Core, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (J.H.); Center for AIDS Research; UCSF Gladstone Institute of Virology and Immunology (P.V.).
² Division of Hematology/Oncology, University of California, San Francisco (N.K.G., C.W., G.M., D.I.A., L.D.K., J.A.L., P.V., J.L.R.); Department of Pathology, University of California, San Francisco (A.N., P.A.T.); Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY (A.O.); Division of Hematology/Oncology, University of California, San Diego (E.G.R.); Division of Hematology/Oncology, San Francisco General Hospital (C.W., D.I.A., J.A.L.); Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL (M.J., J.C.C.); Department of Medicine, Section of Hematology/Oncology, John H. Stroger Jr. Hospital of Cook County, Ruth M. Rothstein CORE Center, Developmental Center for AIDS Research, Chicago, IL (P.G.R.); Department of Internal Medicine, Rush University Medical Center, Chicago, IL (P.G.R.); UCSF Cancer Registry, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (A.G.); Helen Diller Family Comprehensive Cancer Center, University of California San Francisco (D.I.A., J.H., L.D.K., J.A.L., P.V., P.A.T., J.L.R.); Biostatistics and Computational Biology Core, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (J.H.); Center for AIDS Research; UCSF Gladstone Institute of Virology and Immunology (P.V.) [email protected].

Abstract

Background: The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.

Methods: To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).

Results: We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre- versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART.

Conclusion: Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.

Keywords: AIDS; HAART; brain tumor; lymphoma; methotrexate.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Anti-Retroviral Agents / therapeutic use*
Antimetabolites, Antineoplastic / therapeutic use
Central Nervous System Neoplasms / mortality*
Central Nervous System Neoplasms / pathology
Central Nervous System Neoplasms / therapy
Combined Modality Therapy
Cranial Irradiation*
Female
Follow-Up Studies
Humans
Lymphoma, AIDS-Related / mortality*
Lymphoma, AIDS-Related / pathology
Lymphoma, AIDS-Related / therapy
Male
Methotrexate / therapeutic use*
Middle Aged
Neoplasm Staging
Prognosis
Retrospective Studies
Survival Rate

Substances

Anti-Retroviral Agents
Antimetabolites, Antineoplastic
Methotrexate

Abstract

Publication types

MeSH terms

Substances

Grants and funding