An international study, the largest of its kind to date, has found in-depth insights into the diagnosis and treatment of a rare type of cancer known as "immunodeficiency-associated primary central nervous system lymphoma" (ID-PCNSL).
This rare cancer originates from malignant white blood cells and leads to tumor formation in the brain, and rarely in the spinal cord, eyes, or cerebrospinal fluid. It occurs most often in people with weakened immune systems, such as organ transplant recipients, those with autoimmune diseases, or those living with HIV.
Researchers from the Heidelberg Medical School at Heidelberg University had previously demonstrated that this type is not merely a variant of classic lymphoma, but an independent disease entity characterized by specific genetic changes.
The new study, conducted by the International Collaborative Group for Primary Central Nervous System Lymphoma, led by scientists from Heidelberg Medical School and the German Cancer Research Center (DKFZ), analyzed data from 308 patients treated in 23 hospitals across seven countries.
Epstein-Barr virus: A crucial predictive marker
The analysis revealed that the Epstein-Barr virus (EBV) plays a pivotal role in this type of cancer, as it was detected in 79.2% of the tumors examined.
According to Dr. Leon Cowlen, a researcher at Heidelberg University Medical School and the German Cancer Research Center and a physician at Heidelberg University Hospital, virus-positive tumors tend to have a more aggressive course and a worse prognosis, and have shown distinctive imaging features in MRI scans, including different contrast patterns compared to virus-negative tumors.
Scientists have developed a predictive model based on three key factors that can help predict disease progression and patient survival more accurately. These factors are: the presence of the Epstein-Barr virus in the tumor tissue, the patient's age, and their functional status.
The results showed that the combination of these factors largely determines the course of the disease:
When only one risk factor was present, the median survival was 135 months (over 11 years).
When there were two workers, it dropped to 29 months.
When all three factors were present together, it dropped to only three months.
Professor Wolfgang Wick, the study's senior author, head of the Department of Neurology at Heidelberg University Hospital and head of the Clinical Collaboration Unit for Neuro-Oncology, describes this model as a "major advance" that will enable physicians to assess patients more accurately and tailor treatments more effectively to each patient's individual condition.
Until now, there has been no approved standard treatment for this type of cancer. However, the study provided important insights into the most effective treatment approaches. The researchers found that patients whose immune systems could be at least partially rebuilt—either through immunosuppressive therapy or effective treatment for HIV infection—and who received a combined chemotherapy regimen including rituximab and methotrexate, showed a good response rate of 85%. In a significant proportion of these patients, the disease stabilized in the long term and became undetectable.
Dr. Cowlin emphasizes that the interaction between the tumor and a weakened immune system plays a central role, and therefore both aspects should be addressed together in the treatment plan.
Professor Vick concluded by saying that this study provides, for the first time, a strong evidence base for this rare disease, and represents an important step towards applying precision medicine even to rare diseases.
He pointed out that conducting important research into rare tumor entities is often only possible through large international consortia, highlighting the critical importance of international scientific cooperation in this field.
The results were published in the Blood Journal.
