Risk factors for intraocular involvement in patients with primary central nervous system lymphoma

To determine the risk factors for intraocular involvement in patients with primary central nervous system lymphoma (PCNSL), a retrospective chart review was performed on 136 patients who were pathologically diagnosed with PCNSL. The patients were investigated for demographics, clinical manifestation, and the profile of immunohistochemical tumor biomarkers, as well as for the presence of intraocular involvement of lymphoma at diagnosis or during follow-up. The mean age of the entire cohort was 58.6 ± 12.4 years, and the mean follow-up period was 31.1 ± 30.8 months. Twenty-nine (21 %) patients had an intraocular involvement, among which 20 (69 %) patients presented with intraocular involvement at diagnosis of PCNSL and 9 (31 %) patients developed intraocular involvement after a mean period of 32.4 ± 33.6 months. Of the patients with intraocular involvement, 8 (28 %) had no visual symptom at the diagnosis of ocular invasion. Between those with and without intraocular involvement, no significant differences were found with respect to the age, sex, and follow-up period as well as cerebrospinal fluid spread and bone marrow involvement. Among the immunohistochemical biomarkers, the Ki-67 proliferation index was significantly higher in patients with intraocular involvement than in patients without (P = 0.021), but the other investigated biomarkers did not show a significant difference between the two groups. A Ki-67 level ≥80 % was a risk factor for the intraocular involvement in patients with PCNSL (odds ratio, 2.63). Median overall survival was 39.0 months in the entire cohort and was not significantly different between those with and without intraocular involvement (P = 0.959).     

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa,Busulfan, and Cyclophosphamide Conditioning Regimen

BackgroundHigh-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.Patients and MethodsA retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).ResultsThe 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.ConclusionHDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.     

High‐dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high‐dose MTX on treatment‐naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high‐dose MTX (3.5 g/m²) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin‐10 concentration. Adverse events of intravitreal and systemic high‐dose MTX were mild and tolerable. With a median follow‐up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma‐free survival (CLFS) time was 51.1 months. Two‐year CLFS, which was the primary end‐point of the study, was 58.3% (95% confidence interval, 23.0–82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2‐year CLFS was 37.5% (95% confidence interval, 8.7–67.4%). In conclusion, systemic high‐dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).     

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature

BackgroundCentral nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL).Patients and MethodsWe evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen.ResultsThe median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively.ConclusionIn this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.     

Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

This retrospective series explores temozolomide monotherapy in elderly patients with primary CNS lymphoma (PCNSL) and severe comorbidities. In 17 patients (62–90 years old), the complete response rate was 47%, median progression-free survival was 5 months, and median overall survival was 21 months. Five of 17 patients (29.4%) had prolonged responses for at least 12 months and survived for more than 24 months. Three of these patients had a methylated O⁶-methylguanine-DNA methyltransferase (MGMT) promoter, while the MGMT status was not assessable in the remaining two patients. Temozolomide monotherapy appears to be effective in a subgroup of elderly PCNSL patients and deserves further evaluation.     

The value of bone marrow biopsy for staging of patients with primary CNS lymphoma

BackgroundIn patients with presumed primary CNS lymphoma (PCNSL), a systemic manifestation is found only in a small minority. Although bone marrow biopsy (BMB) is recommended for staging, its diagnostic value is unclear.MethodsA retrospective analysis of 392 patients with presumed PCNSL from 3 university hospitals and 33 patients with secondary CNS lymphoma (SCNSL) and initial CNS involvement from a multicenter Germany-wide prospective registry was performed.ResultsA BMB was performed and documented in 320/392 patients with presumed PCNSL; 23 had pathologic results. One harbored the same lymphoma in the brain and bone marrow (BM), 22 showed findings in BM discordant to the histology of brain lymphoma; n = 12 harbored a low-grade lymphoma in the BM, the other showed B-cell proliferation but no proof of lymphoma (n = 5), monoclonal B cells (n = 3), or abnormalities not B-cell-associated (n = 2). In the group of SCNSL with initial CNS manifestation, 32/33 patients underwent BMB; 7 were documented with bone marrow involvement (BMI); 1 had concordant results in the brain and BM with no other systemic manifestation. Six had additional systemic lymphoma manifestations apart from the brain and BM.ConclusionsIn only 2 out of 352 (0.6%) patients with CNS lymphoma (320 presumed PCNSL and 32 SCNSL), BMB had an impact on diagnosis and treatment. While collected in a selected cohort, these findings challenge the value of BMB as part of routine staging in presumed PCNSL.     

Primary T-cell CNS lymphoma presenting with leptomeningeal spread and neurolymphomatosis

Primary CNS lymphoma (PCNSL), a rare form of non-Hodgkin lymphoma that is confined to the brain, is usually of B-cell origin. Primary leptomeningeal lymphoma, regardless of T or B-cell origin, is an unusual site of presentation. Out of 100 consecutive PCNSL patients that we have followed up in our center during the last 10 years, five had T-cell lymphoma (5%). All presented with leptomeningeal involvement as the sole manifestation and four of them presented with neuronal lymphomatosis. Presenting symptoms included signs of elevated intracranial pressure with 6th nerve palsy; headache and bilateral 3rd nerve palsy; mononeuritis multiplex and unilateral hearing loss; bilateral 7th nerve paralysis and bilateral uveitis. Because neither the CSF nor the MRI were indicative, meningeal or nerve biopsies were required for conclusive diagnosis. Four patients died 10-19 months from disease onset and one patient is alive 36 months following the diagnosis. We conclude that T-cell PCNSL can present as an isolated leptomeningeal involvement which may be associated with neurolymphomatosis affecting cranial and peripheral nerves. These manifestations mimic other neurological conditions such as pseudotumor cerebri or vasculitis. Diagnosis is difficult and, as a result, frequently delayed. This calls for early consideration of meningeal or nerve biopsy whenever CSF findings are inconclusive.     

Relevance of intraocular involvement in the management of primary central nervous system lymphomas.

BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are anecdotal. Cases of IOL included in an international multicentre series of 378 immunocompetent patients with primary central nervous system lymphomas (PCNSLs) were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in 170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by chemotherapy in five; one patient was not treated. Chemotherapy included high-dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy. Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was positively correlated to systemic symptoms and meningeal disease. Fifteen patients (71%) achieved an objective response; 16 patients experienced a failure (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less common in patients treated with chemotherapy plus ocular irradiation and was associated with a significantly shorter survival. Seven patients are alive [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of whom were treated with ocular irradiation. The patient with isolated IOL is alive and disease-free at 14 months. OS of the entire series was similar to that of PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually associated with concomitant brain disease and shows a survival similar to that of the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in better control of ocular disease, which seems to be associated with survival. In view of the potential role of ocular irradiation, the use of chemotherapy alone in phase II trials should be critically reconsidered in PCNSL patients with ocular disease.     

Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group Report.

BACKGROUND: Primary intraocular lymphoma (PIOL) is an uncommon subset of primary central nervous system lymphoma. Because it is rare and difficult to diagnose, the natural history and optimal management are unknown. PATIENTS AND METHODS: A retrospective study of 83 HIV negative, immunocompetent PIOL patients was assembled from 16 centers in seven countries. RESULTS: Median age at diagnosis was 65. Median ECOG performance status was 0. Presenting symptoms included blurred vision, decreased visual acuity, and floaters. Median time to diagnosis was 6 months. Diagnosis was made by vitrectomy (74), choroidal/retinal biopsy (6) and ophthalmic exam (3). Eleven percent had positive CSF cytology. Initial treatment was categorized as focal in 23 (intra-ocular methotrexate, ocular radiotherapy) or extensive in 53 (systemic chemotherapy, whole brain radiotherapy). Six received none; details are unknown in one. Forty-seven relapsed: brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Median time to relapse was 19 months. Focal therapy alone did not increase risk of brain relapse. Median progression free (PFS) and overall survival (OS) were 29.6 and 58 months, respectively, and unaffected by treatment type. CONCLUSION: Treatment type did not affect relapse pattern, median PFS or OS. Focal therapy may minimize treatment toxicity without compromising disease control.     

Intraocular lymphoma: report of three cases and review of the literature

Three cases of intraocular lymphoma are presented. One patient had only ocular involvement, one had involvement of the eye and central nervous system, and in the third patient, ocular lymphoma developed 1 year after the diagnosis of a systemic lymphoma. One patient died before treatment could be initiated, but the other two patients responded well to local radiotherapy. Only one patient who received radiation to both eyes and the whole brain, followed by systemic chemotherapy, remains alive 4 years after diagnosis. Eighty-seven cases of intraocular lymphoma reported in the literature are reviewed. Only 16.7% of cases involved the eyes alone without central nervous system or systemic disease. In more than one-half of the cases (59.7%), the eye was the primary site of involvement. Craniotomy or enucleation was required for diagnosis in 52.7% of patients, and diagnosis frequently followed a significant period of delay during which time patients were treated unsuccessfully for uveitis or iritis. Death for most patients was due to progressive central nervous system involvement. Therefore, we recommend combined modality therapy with radiation to the whole brain and both eyes, followed by systemic chemotherapy with or without intrathecal medications.     

Primary treatment and recent survival trends in patients with primary diffuse large B-cell lymphoma of central nervous system, 1995–2016: A population-based SEER analysis

This retrospective cohort study aimed to evaluate primary treatment and recent survival trends in patients with primary diffuse large B-cell lymphoma of central nervous system (CNS) from 1995 to 2016. Using the SEER data, patients diagnosed with non-HIV-associated primary central nervous system lymphoma (PCNSL)–diffuse large B-cell lymphoma (DLBCL) aged ⩾18 years between 1995 and 2016 were identified. The year of diagnosis was divided into the time period-1 (1995–2002), the time period-2 (2003–2012), and the time period-3 (2013–2016). Chi-square tests, the Kaplan–Meier method, log-rank test, and Cox regression model were used in the analysis. Overall, 3760 patients were included. Both the use of radiotherapy alone and the application of combined chemoradiotherapy decreased significantly, following the wider use of chemotherapy alone during 1995–2016. There was a significant improvement in PCNSL cause-specific survival (CSS) (period-1: 13 months vs. period-2: 19 months vs. period-3: 41 months, p < 0.001). Survival of patients aged above 70 years did not change from the time period-1 to the time period-2 (p = 0.101). However, there was an increase in CSS from the time period-2 to the time period-3 in the elderly patients (period-2: 5 months vs. period-3: 9 months, p < 0.001). On multivariable analyses, diagnosed in the time period-3 was significantly and independently associated with better CSS (hazard ratio 0.577, 95% confidence interval 0.506–0.659, p < 0.001). Our analysis shows the use of radiotherapy in the treatment of PCNSL has waned over the study span. There was a significant improvement in CSS during 1995–2016, which reflected developments in treatment over time. The elderly patient population also gained a significant CSS benefit in the most recent period.     

Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study

Background A systemic and intraventricular polychemotherapy regimen (the Bonn protocol) without radiotherapy resulted in durable responses in 75% of patients <60 years with primary CNS lymphoma (PCNSL), but was complicated by a high rate of Ommaya reservoir infections. Here, the efficacy and toxicity of this regimen without intraventricular treatment was evaluated in PCNSL. Patients and methods From August 2003 to November 2005, 18 patients with PCNSL <60 years (median age, 53 years) were treated in a phase II trial with 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. Results Study accrual was prematurely stopped in November 2005 due to a high rate of early relapses. Seventeen of 18 patients were assessable for response: nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu) and two (12%) partial response (PR); four (24%) showed progressive disease (PD). One treatment was stopped due to toxicity. Median follow-up was 23 months, median response duration was only 10 months in responding patients, and median time to treatment failure (TTF) was 8 months in the whole group. Median overall survival (OS) has not been reached. Systemic toxicity was mainly hematologic. Conclusions In PCNSL patients <60 years, polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with intraventricular treatment. H. Pels and A. Juergens contributed equally.     

Utility of post-therapy brain surveillance imaging in the detection of primary central nervous system lymphoma relapse

BackgroundThe optimal follow-up strategy for primary central nervous system lymphoma (PCNSL) patients after first-line therapy is unclear. The goal of this study is to determine the utility of planned brain surveillance imaging in the detection of relapse in a retrospective cohort of PCNSL patients.MethodsPatients were consecutive PCNSL cases treated in Leon Berard Cancer Centre, Lyon, France, from 1985 to 2011. Histology was diffuse large B-cell lymphoma in 94%. Patients were treated by methotrexate (92%) and cytarabine (63%) based-chemotherapy followed by radiotherapy for 108 patients (51%). Clinical records were reviewed for details at relapse and relationship to planned imaging. The imaging follow-up strategy was performed according to each treating physicians.ResultsAmong 209 PCNSL patients, 127 complete response patients entered in post-treatment observation and 63 (50%) subsequently relapsed. Among the 125 evaluable patients, the majority of relapses (N = 49, 80%) was asymptomatic and identified before the planned brain imaging. Surveillance imaging detected relapses before symptoms in 12 patients who entered in post-therapy observation (10%). The median number of brain imaging during the follow-up was 7 (0–13). A total of 819 MRI/CT-scan were performed leading to the detection of 12 asymptomatic relapses. The one year OS rates were 41% and 58% for symptomatic and non-symptomatic relapses, respectively (P = 0.21).ConclusionThe majority of PCNSL relapses occurred outside planned follow-up with no difference in patient outcome between symptomatic and asymptomatic relapses. The role of brain imaging for the detection of relapses in the follow-up of PCNSL patients remains to be clarified.     

The CSF IL-10 concentration is an effective diagnostic marker in immunocompetent primary CNS lymphoma and a potential prognostic biomarker in treatment-responsive patients

IntroductionWe aimed to confirm the diagnostic value and to evaluate the pre- and post-therapeutic prognostic value of cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 in patients with diffuse large B-cell primary central nervous system lymphoma (PCNSL).Patients and methodsIL-10 and IL-6 concentrations were measured in 79 patients with PCNSL at diagnosis and in 40 control individuals. Fifty-four PCNSL patients underwent repeat assessments starting at diagnosis.ResultsThe IL-10 concentration distinguished PCNSL from other neurologic diseases with a sensitivity of 88.6% and a specificity of 88.9% with a cutoff of 4 pg/ml. In a multivariate analysis of PCNSL patients, CSF involvement was associated with a higher IL-10 concentration (mean log (IL-10) of 4.4 versus 2.5 pg/ml, respectively, p = 0.0004). The pre-therapeutic IL-10 concentration had no prognostic impact on outcome. The IL-10 concentration decreased after treatment for most patients tested. Among patients with complete remission or partial remission, as evaluated by magnetic resonance imaging (MRI), a persistent detectable IL-10 level in the CSF at the end of treatment was associated with a negative impact on progression-free survival (PFS) (1-year PFS: 15%, 95% confidence interval [CI]: 2.5–38% versus 59%, 95% CI: 32–78%, respectively, p = 0.0004).ConclusionOur study confirmed that IL-10 is a useful biomarker for the diagnosis of PCNSL. We highlight new findings showing that the IL-10 level in the CSF could be used as a surrogate marker for CSF involvement and that the post-treatment IL-10 concentration could complement standard MRI for therapeutic response assessment in PCNSL.     

Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era

Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement.     

Vitreoretinal Lymphoma: Changing Trends in Diagnosis and Local Treatment Modalities at a Single Institution

IntroductionThe purpose of this study was to report the changing trends in treatment (external beam radiotherapy [EBRT] and intravitreal chemotherapy) of VRL and treatment outcomes at a single institution.Materials and MethodsA retrospective chart review of vitreous biopsy proven patients was performed. The data analysis included demographics, systemic lymphoma status, ocular symptoms, clinical and immunocytological findings, treatment methods, and response (intravitreal methotrexate 300 μg/0.05 mL, 1000 μg/0.1 mL of rituximab and EBRT 36-45 Gy) and ocular and systemic lymphoma outcomes at last follow-up.ResultsTwelve eyes of 8 patients had intraocular B-cell lymphoma (median age, 61 years; range, 50-83). Central nervous system non-Hodgkin's lymphoma (CNS-NHL) was present in 7 of 8 patients. Most common ocular symptoms were diminution of vision in 4 and floaters in 3 patients. Iritis and uveitis were fournd in 6 eyes and vitritis in 11 eyes. Retinal infiltrates were present in 8 eyes. Immunocytology revealed elevated levels of interleukin (IL)-10 (12,783.5 pg/mL), IL-6 (26.7 pg/mL), and IgH gene rearrangement. Three patients were treated with EBRT, 6 eyes with intravitreal methotrexate (median, 9.5; range, 2-15), and 2 eyes with intravitreal rituximab injections (median, 4; range, 2-6). Two patients developed marked keratitis because of methotrexate toxicity. At median follow-up of 33.5 months (range, 4-96), VRL had resolved in 7 eyes and persistent in 5 eyes. One patient died because of advanced CNS-NHL.ConclusionIntravitreal chemotherapy provided good control rates for VRL patients in our limited series. Patients with associated CNS-NHL had poorer outcomes.     

Late relapse in primary central nervous system lymphoma: clonal persistence

Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response and 230 had relapse) with PCNSL who had relapse ≥5 years after initial diagnosis. At initial diagnosis, their median age was 47 years; all patients had brain involvement and achieved a complete response to initial therapy (9 received high-dose methotrexate). Median time to first relapse was 7.4 years (range, 5.2-14.6 y). Eight patients had relapse in the brain, 1 had ocular relapse, and 1 had a systemic relapse. The histologic specimens at initial diagnosis and relapse were examined for clonal rearrangement in 3 patients; 1 had the identical clone at initial diagnosis and relapse 13.8 years later, and the other 2 were uninformative. All patients received salvage therapy (9 received systemic therapy and 1 received intraocular chemotherapy. Nine patients achieved a complete response to salvage therapy and 1 achieved a partial response. Four patients had relapse a second time. The median progression-free survival after first relapse was 31 months (range, 7.9-82.4). Late relapses accounted for 4% of all recurrences (10 of 230 patients) in our PCNSL population. Long-term persistence of the PCNSL clone was observed in one patient. Patients with late relapses have a good response to salvage therapy and prolonged survival.     

Hepatic encephalopathy after treatment with temozolomide

Primary CNS lymphoma (PCNSL) and its variant primary intraocular lymphoma (PIOL) are rare forms of extranodal non-Hodgkin’s lymphoma confined to the CNS including the retina and the optical nerve; histologically, most cases are diffuse large B cell lymphomas. PCNSL in immunocompetent patients display typical radiological features on MRI, i.e. intensely and homogeneously enhancing lesions with moderate edema. Here, we report a 52-year-old male with a history of a PIOL and two consecutive intracerebral relapses who presented with dysarthria, dysphagia, and gait ataxia. Gadolinium-enhanced T1 scans were unremarkable but multiple lesions with restricted water diffusivity were seen on diffusion-weighted imaging. Relapse of his PCNSL was secured histologically only on autopsy. The possible etiology of the diffusion-restricted lesions is discussed.     

Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma

There is currently no standard therapy for recurrent or chemotherapy-refractory central nervous system lymphoma (CNSL). Pemetrexed has been reported to have activity in patients with primary CNSL (PCNSL). The use of pemetrexed in secondary CNS lymphoma (SCNSL) has not previously been reported. Here we retrospectively review the outcomes and toxicities of standard and modified doses of pemetrexed as salvage therapy in 18 PCNSL and 12 SCNSL patients. The overall response rate for PCNSL patients was 64.7 %, all of whom achieved a complete response (CR). The median progression-free survival (PFS) was 5.8 months. For the SCNSL patients, RR was 58.3 % with 2 CR (16.7 %); the median PFS was 2.5 months. Grade ≥3 adverse events included leukopenia in 5 patients (16.7 %), neutropenia in 1 patient (3.3 %), and fatigue in 3 patients (10.0 %). 3 patients died while on treatment, 2 due to infections and 1 due to pulmonary embolism. Our results indicate that pemetrexed has activity as salvage therapy in recurrent PCNSL, even with modified dosing, but outcomes trend towards less favorable in SCNSL.