Identification of central nervous system involvement for patients with AIDS-related lymphomas

May 30, 2014

CHICAGO, IL (May 30, 2014)--Patients with AIDS-related lymphomas (ARL) may face an increased risk of central nervous system involvement (CNSi) compared to other lymphomas. The effect of CNSi on survival outcomes, however, hasn't been thoroughly examined until now.

In a new study led by Fox Chase Cancer Center Hematologist and Oncologist Stefan K. Barta, MD, MS, MRCP, researchers report that CNSi - identified at the time of an ARL diagnosis - does not appear to have an impact on overall survival. Dr. Barta's collaborators will present the findings at the 50th Annual Meeting of the American Society of Clinical Oncology.

In the same study, he and his team found that patients with CNSi at the time of diagnosis were nearly three times as likely, on average, to have CNS relapse (CNSr) during cancer treatment. CNSr is generally associated with particularly poor prognosis.

"It occurs early and usually has a poor outcome, though there are long term survivors," said Dr. Barta. He hopes a better understanding of how CNS involvement affects prognosis could lead to improvements in diagnostic tools and treatments.

Infection with human immunodeficiency virus, or HIV, greatly increases a person's risk of being diagnosed with many lymphomas. AIDS-related lymphomas (ARL), which include diffuse large cell lymphomas and small noncleaved cell lymphomas, are particularly aggressive forms of disease. The vast majority of patients--at least 80 percent, according to the National Cancer Institute--have stage IV disease at the time of presentation. The central nervous system is among the most common sites outside the lymph nodes that may be involved with ARL.

In 2013, as part of a study on factors that influence outcomes for patients with ARL, Dr. Barta led the assembly of a database containing medical data from more than 1500 patients newly diagnosed with AIDS-related lymphomas who participated in clinical trials in Europe and the United States between 1990 and 2010, inclusive.

In the new study, he and his colleagues used the same database to identify 880 patients with ARL whose data included complete information on central nervous system involvement (CNSi) at diagnosis and relapse (CNSr).

They analyzed data to identify associations between CNSr and a variety of patient characteristics, including age, sex, CD4 count, treatment history with cART, lymphoma subtype, rituximab use, and type of initial chemotherapy. Only CNSi conferred a higher risk of relapse.

CNSi was identified in 13 percent of all 880 patients at the time of diagnosis, including 27 percent of patients with Burkitt Lymphoma or Burkitt-like lymphoma and 6 percent in patients with diffuse large B-cell lymphoma. Dr. Barta and his colleagues found that 5.3 percent of patients experienced CNSr a median of 4.2 months after diagnosis; those patients had a median overall survival of 1.6 months.

Sixty-nine percent--607 patients--had been treated with combination anti-retroviral therapies, or cART. These therapies, which came into use in 1996, reversed the dismal survival rates for patients with full-blown AIDS and slowed the onset of AIDS for patients infected with HIV. However, Dr. Barta and his team found that cART did not reduce the frequency of CNSr in patients diagnosed with ARL. Neither did other treatments the patients had received, which included combination chemotherapies with or without rituximab--a monoclonal antibody that acts against B-cells.

"Over the last few years, people have realized that intrathecal CNS prophylaxis is probably inadequate, at least for diffuse large B-cell lymphomas, and many physicians have abandoned it," said Dr. Barta.

Dr. Barta, whose research focuses on ARL, said his findings suggest the approaches used to identify CNS involvement may be missing many patients who are at risk of CNS relapse, and current treatments are insufficient.

"A lot of patients who relapsed probably had undetected CNS involvement at diagnosis," he said. "We want to figure out if there are better strategies to identify patients at risk."
-end-
Barta's coauthors include Jitesh Joshi, Xiaonan Xue, Dan Wang, Joseph A. Sparano, Nicolas Mounier, Josep-Maria Rivera, Christopher Wyen, Kieron Dunleavy, Richard F. Little, Wyndham H. Wilson, and Ariela Noy.Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet status for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, visit Fox Chase's Web site at http://www.foxchase.org or call 1-888-FOX CHASE or (1-888-369-2427).

Fox Chase Cancer Center

Related Lymphoma Articles from Brightsurf:

Oncotarget: An integrative microenvironment approach for follicular lymphoma
Oncotarget Volume 11, Issue 33 features Figure 8, ''Haplotype estimates in follicular lymphoma patients,'' by Assis-Mendonça, et al. which reported that the authors tested associations between SNPs, clinicopathological features and TME composition, and proposed survival models in R-CHOP/R-CVP-treated patients.

Novel Radioimmunotherapy Reverses Resistance to Commonly Used Lymphoma Drug
A new radioimmunotherapy has proven effective in reversing resistance to the most commonly used lymphoma drug, rituximab, according to research published in the October issue of The Journal of Nuclear Medicine.

A new immunotherapeutic agent for children and adolescents with advanced lymphoma
The excellent results of the phase III international paediatric study, Inter-B-NHL ritux 2010, have been published in the New England Journal of Medicine.

Lymphoma's different route revealed
Researchers at the MDC observe the very early stages of blood vessel development in lymph node tumors.

Old weapon, new target: Dasatinib against angioimmunoblastic T-cell lymphoma
Researchers from the University of Tsukuba have shown by in vivo experimentation on a mouse model that angioimmunoblastic T-cell lymphoma is highly dependent on T-Cell Receptor Signaling.

Suspect eliminated as a therapeutic target in B cell lymphoma
Australian researchers have narrowed the focus on which survival proteins are important for the survival of B cell lymphomas, eliminating the protein BCL-W from the 'suspect list'.

New factor in the development of childhood lymphoma
The immune system is highly complex and a detailed understanding of many underlying mechanisms is still lacking.

Antibiotics can inhibit skin lymphoma
New research from the LEO Foundation Skin Immunology Research Center at the University of Copenhagen shows, surprisingly, that antibiotics inhibit cancer in the skin in patients with rare type of lymphoma.

Association of BRCA2 mutations with risk of childhood lymphoma
This research letter reports on the association of BRCA2 gene mutations and potential risk for pediatric or adolescent lymphoma.

Why Hodgkin's lymphoma cells grow uncontrollably
Although classical Hodgkin's lymphoma is generally easily treatable today, many aspects of the disease still remain a mystery.

Read More: Lymphoma News and Lymphoma Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.