Primary central nervous system lymphomas (PCNSL): MRI response criteria revised.
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Central Nervous System Neoplasms↗
Biomedical subjects
Hendrik Pels
Publications and source records attributed to Hendrik Pels.
International study on low-grade primary central nervous system lymphoma.
OBJECTIVE: The aim of this study was to characterize the clinical presentation, course, and outcome of low-grade primary central nervous system lymphoma. METHODS: Cases were assessed in a retrospective series collected from 18 cancer centers in 5 countries. RESULTS: Forty patients (18 men, 22 women; median age, 60 years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or deeper brain structures was seen in 37 patients, only leptomeningeal involvement in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10, and tumor resection alone in 2, whereas 1 patient received no treatment. The median progression-free, disease-specific, and overall survival were 61.5 (range, 0-204), 130 (range, 1-204), and 79 (range, 1-204) months, respectively. Only age 60 years or older was associated with shorter progression-free (p = 0.009), disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate analysis. INTERPRETATION: Low-grade primary central nervous system lymphoma differs from the high-grade subtype in its pathological, clinical, and radiological features. It has a better long-term outcome than primary central nervous system lymphoma in general with age 60 years or older adversely affecting survival.
Age Factors↗
Primary central nervous system lymphoma.
There is no class I evidence for any therapeutic option in primary central nervous system lymphoma (PCNSL). When possible, patients should be included in clinical trials. The role of surgery is restricted to stereotactic biopsy in order to gain material for histopathologic diagnosis. Radiotherapy alone is associated with a median survival of no more than 1.5 years; cure is exceptional. However, in patients aged younger than 60 years, cure is the therapeutic aim. Polychemotherapy based on high-dose methotrexate with deferred radiation results in long-term survival in most of these patients and possibly cure in a substantial fraction of these patients. With regard to chemotherapy in PCNSL, the following must be considered: 1) the most efficient drug in PCNSL is methotrexate at a dosage of at least 1.5 g/m(2) per single dose; 2) methotrexate alone will lead to complete remission in only some patients, whereas the combination of methotrexate with other drugs is more efficient; and 3) the value of additional intraventricular chemotherapy and the necessity of "consolidation" radiotherapy after response to chemotherapy are not yet defined. For patients aged older than 60 years, no curative regimen with acceptable toxicity has yet been established. The combination of radiotherapy with methotrexate-based chemotherapy leads to severe long-term neurotoxic sequelae, ie, cognitive dysfunction, in most older patients and in some patients aged younger than 60 years.
Journal Article↗
Imaging of central nervous system lymphomas with iodine-123 labeled rituximab.
Most patients with primary central nervous system (CNS) lymphoma (PCNSL) relapse after initial response to chemotherapy or the combination of chemotherapy and irradiation. Thus, novel treatment regimens for relapsed PCNSL are needed. As the majority of PCNSL are B-cell neoplasms expressing the CD20 antigen, treatment with the chimeric monoclonal antibody (MAb) rituximab might be reasonable. Nevertheless, the potential efficacy of intravenous rituximab in PCNSL seems to be limited as MAbs are high molecular weight proteins, which might be unable to pass the blood brain barrier. Thus, we performed dosimetric measurements with iodine-123 (123I)-rituximab to evaluate rituximab uptake in PCNSL after systemic intravenous administration. We analyzed four patients with PCNSL receiving a preinfusion of 250 mg/m2 rituximab followed by 200-500 MBq of the gamma-emitter 123I-rituximab. Single photon emission computed tomography (SPECT) was performed 1, 24 and 48 h after administration of the radio-immunoconstruct. Only one patient showed a very weak or questionable uptake of 123I-rituximab into tumor tissue which was ninefold lower compared with the blood-pool accumulation. These data suggest that systemic MAb-based radio-immunotherapy is not feasible in patients with PCNSL because a sufficient activity in the tumor will be associated with severe hematotoxicity. If an uptake of therapeutic rituximab doses into PCNSL can be achieved remains questionable.
Adult↗
VH gene analysis of primary CNS lymphomas.
Primary CNS lymphomas (PCNSL) are highly malignant non-Hodgkin's lymphomas of B cell origin associated with a poor prognosis. These neoplasms show variable sensitivity to radio- and chemotherapy. A molecular basis for these differences in treatment responses has not yet been established for primary CNS lymphomas in a comprehensive series of patients. Here, we performed PCR analyses of the immunoglobulin (Ig) gene rearrangements of 18 PCNSL, including nine patients who responded well to therapy and nine patients who showed resistance to treatment. Variable gene segment distribution, mutation frequency of variable region genes, and clinical course were analyzed. Our data suggest a tendency towards a higher mean mutation frequency (17.2%) in patients responding to treatment and a lower mutation frequency (11.8%) in patients exhibiting a poor response to therapy, respectively. Furthermore, a restricted usage of the VH4 gene family was observed in the majority of nonresponding patients. To further validate the prognostic impact of these molecular parameters, studies in a larger cohort of patients will be required.
Adult↗
Intraventricular treatment of relapsed central nervous system lymphoma with the anti-CD20 antibody rituximab.
Most patients with primary central nervous system (CNS) lymphoma or systemic non-Hodgkin's lymphoma (NHL) involving the CNS relapse after an initial response to treatment, often presenting with leptomeningeal disease. Since the majority of these lymphomas are B-cell neoplasms expressing the CD20 surface antigen treatment with the chimeric monoclonal antibody (Mab) rituximab might be a new therapeutic option. Here, we report on 6 patients with relapsed CNS B-cell lymphoma who were treated with intraventricular or intrathecal applications of rituximab. One of these cases has already been reported.
Adult↗
Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy.
PURPOSE: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. PATIENTS AND METHODS: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)-based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C. RESULTS: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%). CONCLUSION: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.
Adult↗
Cognitive performance and magnetic resonance imaging findings after high-dose systemic and intraventricular chemotherapy for primary central nervous system lymphoma.
BACKGROUND: Long-term neurotoxicity is a frequent complication of combined radiotherapy and chemotherapy in patients with primary central nervous system lymphoma. Treatment protocols without radiotherapy have been implemented to avoid this; however, little detailed neuropsychologic and neuroradiologic data exist to assess the frequency of long-term treatment sequelae in this patient group. OBJECTIVE: To determine whether a polychemotherapy regimen based on high-dose methotrexate results in cognitive impairment and/or changes detectable by magnetic resonance imaging of the brain during long-term follow-up. PATIENTS AND METHODS: Twenty patients with histologically proven primary central nervous system lymphoma were treated with a novel chemotherapy protocol that included systemic and intraventricular administration of methotrexate and cytarabine (ara-C). Standardized neuropsychologic testing and magnetic resonance imaging investigations were performed prior to therapy and prospectively during a median follow-up period of 36 months (range, 21-69 months). RESULTS: Ten patients achieved durable remissions without relapse for more than 1 year after completion of chemotherapy. There was no gross cognitive decline in any of these patients during the follow-up period. In contrast, magnetic resonance imaging revealed therapy-induced white matter changes in 5 of these patients. CONCLUSIONS: We conclude that chemotherapy alone is associated with a low risk of long-term neurotoxicity in primary central nervous system lymphoma. Methotrexate-induced white matter lesions detectable on magnetic resonance imaging are not inevitably associated with significant cognitive decline.
Adult↗
Treatment options of AIDS-related lymphoma.
Recently, the median survival of patients with AIDS-related lymphoma has changed significantly. This effect is mainly because of changes in the use of antiviral (highly active antiretroviral therapy; HAART) or chemotherapy regimens. Several novel treatment options have been explored in patients with lymphoma. It is hoped that innovative strategies will lead to a survival benefit in these patients. In this review, we present an update of current strategies for the treatment of AIDS-related lymphoma.
Antineoplastic Agents↗
Intensified PCV-chemotherapy with optional stem cell support in recurrent malignant oligodendroglioma.
Six patients with recurrent or progressive anaplastic oligodendroglial tumors after surgical treatment and irradiation were treated with six/seven cycles of intensified PCV: Vincristine (1 mg/m(2)), CCNU (50 mg/m(2)) d.1,15 and procarbazine (75 mg/m(2)) d.2 to 29. If leukocytopenia (< 2.500/microl) or thrombocytopenia (< 75.000/microl) developed, 1 x 10(6) CD34(+) autologous stem cells/ kg body weight were reinfused three days after completion of subsequent cycles. Complete response was seen in 2/6 and partial response in 4/6 patients. Median follow up from time of recurrence was 35 months, progression free survival was 18 to > 39 months and overall survival 23 to > 39 months. We conclude that intensified PCV with stem cell support is feasable in recurrent/progressive anaplastic oligodendroglial tumors and appears to be sufficiently well tolerated to allow further study.
Adult↗