Although it is rare and the prognosis for patients is often poor, the presence of central nervous system involvement at the time of diagnosis of mantle cell lymphoma is not always immediately fatal, according to findings from an international study.

According to the European Mantle Cell Lymphoma Network (EMCLN) findings, the crude prevalence of CNS events was 0.9% at the time of diagnosis and 4.1% at any time. The multicenter, retrospective study found that the median time to a CNS event’s occurring was 15.2 months, with an overall survival of 3.9 months after the event was identified, but some patients were still alive 2 years later.

Dr. John Seymour

“We now have some better descriptors about what the expectations and outcome of patients with central nervous system involvement are,” Dr. John Seymour said in an interview at the annual congress of the European Hematology Association.

Dr. Seymour, professor and chair of the hematology service at Australia’s Peter MacCallum Cancer Centre in East Melbourne, Victoria, added that even though the overall prognosis of patients who develop CNS involvement is very poor, there are some patients who do better than others.

There is “a subgroup [of patients] who are able to receive high-dose ara-c [cytarabine] or high-dose methotrexate treatment, who are young and fit enough, who do somewhat better,” Dr. Seymour said. “A proportion will be alive at 2 years, so it’s not an inevitably, rapidly fatal, and … futile situation.”

Mantle cell lymphomas are a rare type of non-Hodgkin’s lymphoma (NHL), accounting for just less than 3% of all NHL cases in the United States and affecting primarily more elderly patients (Cancer 2008;113:791-8).CNS involvement is also a rare and often devastating event, but it has not previously been very well characterized. As a result, it’s not known whether CNS prophylaxis is of benefit to patients.

The aim of the EMCLN study, therefore, was to look at the problem in more detail, to determine the prevalence of CNS involvement, and to look for any clinically defining features, effect of treatment, and patient outcomes.

A retrospective database review by EMCLN members in 12 centers identified 1,396 patients with mantle cell lymphoma, of whom 1,339 had no CNS involvement. Of the 57 patients with CNS involvement, most (44) developed it at some point during the course of their follow-up.

At diagnosis of mantle cell lymphoma, the patients who developed CNS involvement had a median age of 61 years, but this ranged from 38 years to 82 years; patients were predominantly men (70%), with stage IV (91%) disease, and 28% had blastoid histology. Isolated CNS involvement occurred in 15 cases.

Prominent features were a high MIPI (Mantle Cell Lymphoma International Prognostic Index) score (61% of cases), a Ki-67 greater than 30% in 69% of patients, and increased beta2-microglobulin and lactate dehydrogenase in 77% and 75% of cases, respectively. The bone marrow and the peripheral blood were the most common extranodal sites involved, affecting two or more sites in 61% of patients.

At diagnosis of CNS involvement, patients’ neurologic symptoms included weakness, altered mental state, headache, and ocular problems such as double vision. Other symptoms – such as sensory disturbances, pain, sciatica, dizziness, vertigo, ataxia, seizure, and dysphagia – occurred but were less frequent.

CSF cytology and flow cytometry showed a high sensitivity for identifying CNS involvement, with 85% having positive cytology and 91% a positive flow cytometry result.

“Patients had a range of chemotherapies prior to developing central nervous system involvement, but receipt of these regimens was not totally protective,” Dr. Seymour said. Data were not collected to enable the relative risk of CNS development with the regimens received.

Chemotherapy was the most frequent treatment strategy to allay CNS disease (67%), and some patients did appear to achieve a complete remission of the CNS disease as a result. In an exploratory analysis, these patients also tended to have improved overall survival, as did those with lower white cell counts (less than 10.9 x 109/L), and who received treatment with high-dose antimetabolites.

“In the longer term, these data will provide a foundation for us to identify predictive factors, to identify – ahead of the event – those people at increased risk,” Dr. Seymour said, adding his hope that this will allow preventive steps to be taken.

Dr. Seymour had no conflicts of interest.