The study population included 65 patients newly diagnosed with PCNSL at Asan Medical Center, Seoul, Korea, between November 1995 and August 2010. Patient characteristics including age, Eastern Cooperative Oncology Group (ECOG) PS, international prognostic index (IPI), and treatment information were collected from the ASCT data registry at our center.

Staging evaluations for each patient involved a physical examination, including slit-lamp assessment by an ophthalmologist; contrast-enhanced magnetic resonance imaging (MRI) of the brain; computed tomography (CT) of the thorax, abdomen, and pelvis; lumbar puncture and cerebrospinal fluid (CSF) cytology; bilateral bone marrow (BM) aspiration and biopsy; serology test for HIV; complete blood cell count with differential count; liver and kidney function tests; and serum lactate dehydrogenase (LD) level measurements. Lumbar puncture was not performed in patients suspected of having increased intracranial pressure.

Responses to treatment were assessed according to the criteria of the International Group for PCNSL [8]. Routine follow-up imaging analysis (MRI of the brain and CT) and ophthalmologic exams were performed every 3 months or whenever clinically indicated.

Patient characteristics were described using summary statistics, as medians and ranges, or as proportions. Overall survival (OS) was calculated from the date of diagnosis, to the date of death from any cause or the date of last follow-up for surviving patients. Failure-free survival (FFS) was calculated from the date of diagnosis to date of relapse, progression of disease, death from any cause, or last follow-up. OS and FFS were estimated using the Kaplan-Meier method and compared using the log-rank test. Two-tailed P-values<0.05 were regarded as statistically significant.

The IELSG prognostic scoring system is composed of 5 prognostic variables: age more than 60 years, ECOG score more than 1 (Karnofsky performance status [KPS] <70%), elevated serum LD level, high CSF protein concentration, and involvement of the deep regions of the brain (periventricular regions, basal ganglia, brainstem, and/or cerebellum) [7]. Due to the retrospective nature of this study, resulting in incomplete data, we assessed only the prognostic significance of patient age, ECOG PS, and serum LD level.

The MSKCC prognostic score is a simplified index, including age and KPS [6], with 3 distinct prognostic classes: class 1 (age<50 years), class 2 (age≥50 years or KPS≥70%), and class 3 (age≥50 years and KPS<70%). This scoring system was also used for prognostic analysis.

The clinical characteristics of the 65 patients are summarized in Table 1. Their median age was 55 years (range, 26-77 years). Of these, 63 tumors were histologically diagnosed as diffuse large B-cell lymphoma and 2 as T-cell lymphomas (T-lymphoblastic lymphoma and peripheral T-cell lymphoma). All patients had parenchymal brain disease, and 10 patients (15.4%) had extracranial involvement including 7 with positive CSF cytology, 2 with ocular involvement, and 1 with a spinal cord lesion. Twenty-nine (44.3%) patients received chemotherapy alone (CTx) as first-line treatment, while 13 (20.0%) received CTx followed by whole brain radiotherapy (WBRT) and 18 (27.7%) received CTx followed by ASCT. Two patients with HIV infection received only palliative WBRT, and 3 received best supportive care without any chemotherapy or radiation therapy because of poor PS. No difference in patient characteristics was observed between those treated with and without ASCT (data not shown).

As shown in Table 2, 62 of the 65 patients received first-line treatment with curative intent. The overall response rates (ORR) in patients receiving CTx alone, and CTx followed by WBRT, were 62.1% and 84.6%, respectively. All patients who received chemotherapy followed by ASCT achieved clinical response; of these 77.8% showed complete response (CR) and 12.2% showed partial response (PR). Among the 18 patients treated with CTx followed by ASCT, 5 patients showed PR after CTx, but finally achieved CR after ASCT. The ORR (P=0.031) and CR rate (P=0.025) were significantly higher in patients treated with chemotherapy followed by ASCT than in those treated without ASCT (Table 2).

After a median follow-up duration of 18.8 months (range, 1.1-138.0 months), 31 of the 65 patients had died including 21 from progression or relapse of PCNSL. The median FFS was 13.0 months (95% confidence interval [CI], 3.5-22.8 months) and the median OS was 36.1 months (95% CI, 20.5-51.7 months). The 2-year FFS and OS rates were 42.0% and 66.5%, respectively (Fig. 1). Four treatment-related deaths occurred in patients who received HD-MTX chemotherapy.

The 3 patients who received best supportive care without other treatment showed progression of intracranial lesions, with 1 patient dying from severe pneumonia. Following first-line treatment, 6 patients (9.2%) experienced progression of disease, and 25 (38.5%) experienced relapse of disease, including 21 with brain parenchymal lesions, 1 with an ocular lesion, and 3 with positive CSF cytology (Table 3). No systemic relapse was observed without a CNS lesion.

Following failure of first-line treatment, 33 patients received salvage treatment, including 15 who received salvage CTx, 4 who received salvage CTx followed by ASCT, 11 who received WBRT, and 3 who received best supportive care alone.

FFS was not related to patient age, ECOG PS, serum LD level, or MSKCC prognostic score. Age less than 60 years (P=0.001), ECOG PS ≤1 (P=0.019), and lower MSKCC prognostic score (P=0.001) were related to prolonged OS (Table 4 and Fig. 2). However, patients who received HDC followed by ASCT showed significantly better FFS (58.6 months vs. 9.1 months; P=0.006) and OS (58.6 months vs. 33.3 months; P=0.034) than those who did not (Fig. 3).

Multivariate analysis showed that ASCT was an independent predictive factor for better FFS (hazard ratio [HR], 0.348; 95% CI, 0.151-0.084), but not for OS (Table 5). Age equal to or more than 60 years was the only independent prognostic factor for OS (HR, 2.968; 95% CI, 1.269-6.939). The MSKCC prognostic score was also predictive of patient survival in multivariate analysis.