Methotrexate and Temozolomide Plus Intrathecal Liposomal Cytarabine for Primary or Secondary Central Nervous System Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4899-4899
Author(s):  
Lorenzo Falchi ◽  
Marco Gunnellini ◽  
Ilaria Angeletti ◽  
Laura Franco ◽  
Anna Marina Liberati
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Contrast Enhancement ◽  
Cell Lymphoma ◽  
Cns Lymphoma ◽  
Liposomal Cytarabine ◽  
Delayed Neurotoxicity ◽  
Cns Prophylaxis

Abstract Abstract 4899 Treatment of central nervous system (CNS) lymphoma remains challenging, and balance between therapeutic effectiveness and toxicity is difficult to find. The addition of systemic chemotherapy to whole brain radiotherapy has significantly improved the outcome of these patients. However, this combined strategy is burdened with possible acute and/or delayed severe neurotoxicity, particularly in elderly patients. Chemotherapy-only approaches, with or without concomitant intrathecal (IT) therapy, for CNS lymphoma have been explored. Moreover, deferring radiotherapy to the time of first or subsequent relapse may reduce the risk of severe neurotoxicity, without altering outcome. Recently, high-dose methotrexate and temozolomide (HD-MTX-TMZ) without IT CNS prophylaxis have been studied in PCNSL elderly patients. This regimen appears effective, while substantially decreasing acute and/or delayed neurotoxicity. Conflicting data exist regarding the safety of combining IT liposomal cytarabine (LC) and systemic CNS-penetrating therapy. We report our preliminary experience with HD-MTX-TMZ plus IT LC used upfront or as salvage in 4 primary or secondary CNS lymphoma patients, only one of which under the age of 60 (56). Treatment consisted of induction: MTX 3g/ms d 1, 10, 20, TMZ 100 mg/ms d 1–5; and maintenance for ≥SD patients, and for up to 5 additional cycles: MTX 3g/ms d 1, TMZ 100 mg/ms d 1–5, every month. Fifty mg IT LC were given concomitantly for up to 6 doses planned. LC doses were separated by at least 14 days from one another and at least 7 days from HD-MTX. Pt n. 1 (56 year-old male) had a history of testicular diffuse large B cell lymphoma (DLBCL), stage IVA. He received chemo-radiotherapy with 4 concomitant IT LC injections as CNS prophylaxis. Complete response (CR) was achieved. Two months later, he presented with headache and dizziness. MRI and PET revealed metabolically active righ cerebellar lesion. Karnofsky performance status (KPS) was 50%. Rituximab plus TMZ and IT MTX were initiated but soon discontinued due to a G4 CMV-related pneumonia. After complete recovery, HD-MTX-TMZ was started with concomitant 4 IT LC injections, and precautionary stem cell harvest. No significant G3-4 toxicities were observed during treatment. At 9 months of follow-up post-treatment, the lesion is stable with no contrast enhancement at MRI and PET is negative, suggesting a CRu. Pt 2 (76 year-old male) was referred in May 2009 with a diagnosis of CNS peripheral T-cell lymphoma not otherwise specified with MRI- and PET-documented multiple brain localizations (i.e. hypophyseal infundibulum, cavernous sinus, cerebellum). KPS was 60%. He was treated with systemic steroids and TMZ 150 mg/ms d 1–5/28. In August 2009 disease progressed after two cycles, and HD-MTX-TMZ was started. IT LC was added as CNS prophylaxis with 4 drug injections. Toxicity consisted of G2 renal insufficiency and G3 steroid-induced diabetes mellitus, both resolved. Treatment resulted in marked shrinkage of all lesions, with no contrast enhancement and PET is negative, indicating CRu, which is stable at 5 months of follow-up. Pt 3 (68 year-old female) was diagnosed with PCNSL, DLBCL, with left cerebellar localization. KPS was 50%. HD-MTX-TMZ and concomitant IT LC injections were initiated as first-line therapy. Four maintenance cycles and 5 IT LC injections have been performed so far. Toxicities included G3 atrial fibrillation. Interim MRIs documented very good partial remission of the disease. Pt 4 (71 year-old female) was diagnosed with DLBCL stage IIIE (i.e. subcutaneous facial localization) in July 2009, and treated with R-COMP (liposomal doxorubicine in lieu of the free formulation) for 8 cycles. She obtained CR, but in July 2010 presented with aphasia and facial hemiparesis. Brain MRI showed multiple subcortical lesions in both hemispheres, biopsy-confirmed to be lymphoma. The first IT LC injection and HD-MTX dose were given without significant toxicity. All patients completed induction and 5 maintenance cycles. HD-MTX-TMZ and concomitant IT LC therapy appeared feasible and overall well tolerated. No acute neurologic complications were observed. Follow-up is too short to make comments on delayed neurotoxicity. Increasing the number of LC injections might be reasonable and at least 7 days should be interposed between systemic and IT therapy. HD-MTX-TMZ plus IT LC deserves further evaluation in a larger prospective setting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3479
Author(s):  
Andrea Morales-Martinez ◽  
Fernando Lozano-Sanchez ◽  
Alberto Duran-Peña ◽  
Khe Hoang-Xuan ◽  
Caroline Houillier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Current Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

scholarly journals Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy

2018 ◽  
Vol 5 (3) ◽  
pp. 176-183
Author(s):  
Roy E Strowd ◽  
Gregory Russell ◽  
Fang-Chi Hsu ◽  
Annette F Carter ◽  
Michael Chan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Influenza Vaccine ◽  
Elderly Patients ◽  
Influenza Vaccination ◽  
Standard Dose ◽  
High Grade Glioma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Central Nervous System Malignancy

Abstract Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

Liposomal Cytarabine in the Central Nervous System (CNS) Prophylaxis of Elderly Patients with Aggressive B-Cell Non-Hodgkin’s Lymphoma (NHL) and Undifferentiated Acute Leukemia (UAL): Preliminary Results of a Single-Center Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4663-4663 ◽  
Author(s):  
Barbara Anaclerico ◽  
Velia Bongarzoni ◽  
Anna Chierichini ◽  
Maurizio Bartolini ◽  
Piero Iacovino ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
Disease Stage ◽  
Liposomal Cytarabine ◽  
Line Treatment ◽  
Cns Involvement ◽  
Cns Prophylaxis

Abstract Background: CNS involvement in acute lymphoblastic leukemia/AUL is a well-recognized event and CNS prophylaxis is considered mandatory. In NHL, meningeal relapse occurs more rarely, ranging from 4–14% depending on histology, anatomical location and biological parameters. Flow cytometric analysis of cerebrospinal fluid (CSF), however, detected occult lymphomatous meningitis in 22% of NHL cases at risk at diagnosis (Hegde et al. Blood2005;105:496). CNS prophylaxis is currently recommended only in high-risk disease (stage IV/high IPI score) and in patients with extranodal NHL. Sustained-release liposomal cytarabine (DepoCyte®), which is licensed for meningeal relapse in NHL, has proved effective in treating lymphomatous and leukemic meningitis (Glantz et al. J Clin Oncol1999;17:3110; Sancho et al. Haematologica2006;91:ECR02). Intrathecal (IT) liposomal cytarabine is distributed throughout the CSF and has an extended half-life, allowing administration once every 2–4 weeks (Chamberlain et al. Arch Neurol1995;52:912). We therefore tested the efficacy of liposomal cytarabine in CNS prophylaxis for elderly patients with aggressive NHL or AUL, with the aim of testing the safety of IT treatment in elderly patients and the efficacy of liposomal cytarabine in preventing lymphoma/leukemia CNS relapse. Methods: From June to November 2005, 4 patients > 70 years of age entered the study. Diagnoses were: 2 stage IV, IPI 3, diffuse large B-cell lymphoma (DLBCL); 1 mantle cell lymphoma (MCL), and 1 AUL; 2 patients had extranodal bulky disease (1 psoas muscle, 1 retro-orbital plus paranasal sinus involvement). As first-line treatment, the 3 NHL cases were given R-CHOP every 21 days for 6 cycles. The patient with AUL received conventional 3-drug induction (vincristine/idarubicine/prednisone) every week for 3 weeks, followed by 3 courses of L-VAMP (vincristine/cytarabine/intermediate-dose methotrexate/leucovorin rescue) and then conventional maintenance (6-mercaptopurine/methotrexate and monthly re-induction with vincristine/prednisone). All patients received CNS prophylaxis with IT liposomal cytarabine 50 mg followed by systemic steroid injection. In NHL cases, IT therapy was given the day before systemic chemotherapy for a total of 4 administrations; in AUL, prophylaxis was given every 4 weeks during induction and maintenance for a total of 6 doses. Results: Three (2 NHL and 1 AUL) patients achieved a complete response (CR) and 1 (NHL) achieved a partial response, with response durations of 4, 5, 6+ and 8+ months, respectively. As of July 2006, after a median follow-up of 10 months (range 9–12), all patients were alive; 2 (1 DLBCL, 1 AUL) were in continuous CR, and 2 (1 DLBCL, 1 MCL) had progressive disease and were receiving second-line treatment. Isolated relapse of leukemia/lymphoma in the CNS was not seen. Liposomal cytarabine was well tolerated; no drug-related side effects or hematological toxicities were recorded. Conclusions: As occult CNS involvement has been shown to occur in >20% of newly diagnosed patients with high-risk NHL, flow cytometry and cytospin analysis of CSF at diagnosis should be implemented in order to adequately target CNS prophylaxis. Liposomal cytarabine should be the drug of choice for CNS prophylaxis, particularly in elderly patients.

scholarly journals Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma

Cancer ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 4283-4290 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Matthew Hellmann ◽  
Jeffrey A. Barnes ◽  
Peter Hammerman ◽  
Christiana Toomey ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

scholarly journals Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in limited cutaneous sclerosis: a rare disease combination

2019 ◽  
Vol 12 (1) ◽  
pp. e226259
Author(s):  
Sucharita Anand ◽  
Animesh Das ◽  
Surjyaprakash Shivnarayan Choudhury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rare Disease ◽  
Posterior Fossa ◽  
Neurological Disease ◽  
Neurological Deficits ◽  
Cns Lymphoma ◽  
Rare Association ◽  
Insidious Onset

A 26-year-old patient of limited cutaneous sclerosis presented to us with insidious-onset posterior fossa symptoms of headache, vomiting, vertigo and gait imbalance, progressing over a period of 3 weeks. A diagnosis of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids was made by combining the clinical features with radiological evidence showing punctate infiltration of the pons, brainstem and cerebellum. Relevant differentials in the form of neurosarcoid, infections, central nervous system (CNS) lymphoma and Neuro-Behcet’s disease were ruled out by history and investigations. The patient responded dramatically to steroid therapy, and had no neurological deficits after 18 months of follow-up. This case highlights the rare association of a not-so-common immunological disease with a rare neurological disease.

scholarly journals Non-Diffuse Large B-Cell Primary Central Nervous System Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4208-4208
Author(s):  
Sangeetha Gandhi ◽  
Grzegorz S. Nowakowski ◽  
Thomas M. Habermann ◽  
Kay M. Ristow ◽  
Patrick Johnston
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
Ecog Performance Status ◽  
Kaplan Meier ◽  
Large B Cell

Abstract Background: The majority of subjects with a diagnosis of primary central nervous system lymphoma (PCSNL) have diffuse large B-cell lymphoma (DLBCL) as their histology. However, there are a sub-set of PCSNL patients who present with other histologies. This retrospective study was conducted to evaluate histological morphology, risk factors and clinical course in subjects with non-diffuse large B-cell primary CNS lymphoma. Methods: We used the Mayo Clinic Lymphoma Database to search for patients with PCSNL during the time period from January 1995 to June 2018. One hundred and fifty nine patients met the criteria and underwent record review. One hundred and nine patients were excluded as they had PCSNL with DLBCL histology (N=47, 43%), secondary central nervous system lymphoma (N=56, 51%) and post-transplant lymphoproliferative disorders (PTLD) with DLBCL morphology (N=6, 5%). We identified fifty patients with PCSNL Non-DLBCL histology, by evaluating the biopsy reports. We abstracted clinical data and outcomes for these groups through medical chart review. Kaplan-Meier analysis was used to estimate survival. Results: The mean age of the study population was 70 ± 11.3 years and 66% were male. Of the 50 patients, the most common histology was low grade CNS lymphoma (N=14, 28%) while Hodgkin's lymphoma (N= 1, 2%), Burkitt's lymphoma (N= 1, 2%) and histiocytic lymphoma (N= 1, 2%) were the least common. The frequencies of other PCSNL Non-DLBCL histology are demonstrated in Table1. Most patients showed good ECOG performance status of 0-2 and four patients had ECOG performance status of grade 3 (N=4, 8%). Six of the patients were immunocompromised (N=6, 12%), PPD positive tuberculosis; corticosteroids and PTLD with DLBCL histology were the causes for the immunocompromised state. The location of the CNS lymphoma included brain (N=24, 50%); spinal cord (N=9, 18%); orbits (N=5, 10%); deep structures which included brainstem, cerebellum, cerebellopontine angle and cauda equina (N=5, 10%); leptomeninges (N=4, 8%) and neural involvement which included sciatic, peroneal and facial nerve (N=3, 6%). CSF examination revealed increased protein levels (N=10, 20%), malignant cells (N=11, 22%), negative cytology (N=14, 28%) and unknown or not done (N=15, 30%). Most patients presented with neurological symptoms such as seizures, peripheral neuropathy (numbness/weakness/tingling), headache, confusion & cognitive disturbances (memory changes), gait disturbances (difficulty with balance/ataxia), visual disturbances (blurry vision) and paraplegia, but none of them presented with B-cell symptoms such as fever, night sweats and weight loss. Treatment modalities included chemotherapy, radiation and surgery. Fourteen patients underwent radiation therapy (N=14, 28%); three of the patients had undergone surgery of which the patient with peripheral T-cell lymphoma had undergone a complete excision, the patient with marginal zone lymphoma had undergone debulking with subtotal craniotomy and the patient with MALT lymphoma had undergone resection with gamma knife. Table 2 demonstrates the various chemotherapy drugs used and the distribution of frequency of biopsy, radiation and surgical treatment in the different pathology of PCSNL Non-DLBCL. The median overall survival period using Kaplan-Meier analysis showed that Burkitt's Lymphoma had the least median time survival of less than a month and PTLD had the highest median survival of 146.25 months (p=0.0017). Table 3 shows the median survival time for all the different pathology's of PCSNL Non-DLBCL. Conclusion: This retrospective study reinforces the critical need for a histologic diagnosis when a patient is diagnosed with PCNSL. PCSNL is considered to be DLBCL but there are other histology's that could potentially be PCSNL and the treatment should be tailored to the individual patient's histology. Disclosures No relevant conflicts of interest to declare.

Outcomes in mantle cell lymphoma with central nervous system involvement.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19527-e19527
Author(s):  
Nicole McLaughlin ◽  
Yucai Wang ◽  
David James Inwards ◽  
Jose Caetano Villasboas ◽  
Ivana N. M. Micallef ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Bone Marrow Involvement ◽  
Central Nervous System Involvement ◽  
Response To Therapy ◽  
Cns Lymphoma ◽  
Cell Transplant ◽  
Cns Involvement ◽  
Btk Inhibitors

e19527 Background: While extra nodal involvement by MCL is relatively common, involvement of the central nervous system (CNS) is a rare ( < 5% of cases) complication with limited treatment options. We report the outcomes of a large cohort of patients (pts) with CNS MCL. Methods: MCL pts with CNS involvement seen at Mayo Clinic between 1/1/1995-9/16/2020 were identified. CNS involvement was defined by histologically confirmed CNS MCL, CSF analysis demonstrating lymphoma cells, and/or neuroimaging findings compatible with CNS lymphoma. Medical records were reviewed for baseline characteristics, treatment, and outcome. Kaplan-Meier method was used for time to event analysis. Results: Out of 1,753 pts with MCL, 36 (2%) had CNS involvement by MCL. Median age at MCL diagnosis was 64 years (range 36-83) and 26 were male (72%). At MCL diagnosis, non-CNS extranodal involvement was seen in 30 pts, 24 with 1 site and 6 with ≥ 2 sites; 24 had bone marrow involvement. 11 (31%) pts had blastoid variant. Median Ki-67 was 40% (range 15-100%). MIPI score was available in 17 pts [low risk (n = 5, 29%), intermediate risk (n = 9, 53%), high risk (n = 3, 18%)]. The most common frontline regimen for MCL was R-CHOP and 14 (39%) pts underwent autologous stem cell transplant in CR1. The incidence of CNS involvement was overall similar over the study period. Median time from MCL diagnosis to CNS involvement was 25 months (m) (range 0-167). 4 (11%) pts presented with CNS involvement at initial diagnosis and 32 presented at relapse (12 isolated CNS relapse and 20 concurrent CNS and systemic relapse. Abnormal CSF was noted in 27 (87%) pts [consistent with MCL diagnosis (n = 26), atypical lymphocytes (n = 1)]. Abnormal CNS imaging was reported in 27 (75%) pts [leptomeningeal (n = 18), leptomeningeal and parenchymal (n = 5), parenchymal (n = 2), ocular (n = 2)]. First line CNS-directed therapy data was available in 33 (92%) pts. 12 (34%) received intrathecal (IT) therapy alone, 19 (54%) received systemic +/- IT therapy, 2 (6%) received radiation alone, and 2 (6%) pts received no treatment (hospice). The overall CNS response to therapy was CR in 13 (42%) pts, PR in 3 (10%), SD in 8 (26%), and PD in 7 (22%) pts. Three pts received BTK inhibitors [ibrutinib (n = 2) or acalabrutinib (n = 1)] as the first CNS-directed therapy. One patient achieved a CR with a response lasting 4 m, another patient achieved a PR with response lasting 10 m. CNS response data was not available in the remaining pts. Median follow up from CNS involvement was 72 m (95% CI: 41-NR). Median EFS for the 1st CNS-directed therapy was 3.7 m (95% CI: 1.6-6.1). At last follow up, 30 pts were deceased. The cause of death was CNS lymphoma in 10 (33%) pts and systemic lymphoma in 9 (30%) pts. Median OS from CNS involvement was 4.7 m (95% CI: 2.3-6.7). Conclusions: CNS involvement by MCL has dismal outcomes as evident by a median OS of approximately 5 m. BTK inhibitors may have a role in treatment of this rare complication, but further prospective investigation is needed.

Soluble Human Interleukin-2 Receptor (SIL-2R) as a Potential Predictor for Central Nervous System Relapse In Patients with Diffuse Large B-Cell Lymphoma In Rituximab Era: A 4.4-Year Follow up Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2814-2814
Author(s):  
Noriko Nishimura ◽  
Masahiro Yokoyama ◽  
Kengo Takeuchi ◽  
Eriko Nara ◽  
Kenji Nakano ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

Abstract Abstract 2814 Background: Central nervous system (CNS) relapse is considered an infrequent but severe, nearly fatal complication of diffuse large B-cell lymphoma (DLBCL) following initial chemotherapy. Intrathecal (IT) prophylaxis cannot be recommended for all DLBCL patients because of the low probability of CNS relapse. Rituximab (R) added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been reported as likely to reduce the frequency of CNS relapse in patients with DLBCL, however, the efficacy of rituximab on the prognosis of CNS relapse compared with those who relapsed at other sites and predictive factors for CNS relapse in patients treated with rituximab contained chemotherapy remain unclear. The main objective was to determine the high-risk patients who need IT prophylaxis and the outcomes of CNS relapse compared with relapse on other sites. Patients and Methods: Diffuse large B cell lymphoma patients treated with rituximab contained CHOP regimen with or without radiotherapy and IT prophylaxis at Cancer Institute Hospital of JFCR between October 2003 and December 2006 were analyzed retrospectively. CNS relapse was defined as leptomeningeal, brain parenchymal, or intradural involvement with lymphoma, based on radiological findings or the presence of malignant lymphoma cells in spinal fluid. Results: A total number of 137 patients were identified. IT prophylaxis was administered in 13 of 137 patients (9.48%) depending on the sites of lymphoma involvement, such as bone marrow involvement, testis, paranasal sinuses. 17 of 137 patients (12.4%) underwent radiotherapy after chemotherapy because of early stage or their residual disease. With a median follow-up period of 4.4 years, 9 patients had experienced CNS relapse (6.7%: 3.0–12.1, 95%CI) among 30 documented relapses, with 9 presenting with nodal relapse alone and 21 presenting with extranodal relapse including CNS. IT prophylaxis and the addition of radiotherapy did not affect the frequency of CNS relapse (P=0.6 and 0.26). Median time to CNS relapse was 20 months. Overall survival (OS) was significantly inferior in CNS relapse patients to other-sites relapse patients, (median OS, 61 months vs. did not occur; P =.042). Nevertheless, OS was not significantly different between patients with CNS relapse or at other sites. In univariate analysis, factors associated with CNS relapse (P < 0.05) included age over 65 years and serum levels of soluble IL-2 receptors (sIL-2R) ≧10 ULN (upper limit of normal) but not sex, PS ≧3, stage ≧4, B symptom, bulky mass, elevated LDH >2 ULN, elevated MIB1 index ≧90%, poor revised-international prognostic index (R-IPI), extranodal sites ≧2, or type of GC or non-GC. Multivariate Cox regression analysis identified increased serum levels of (sIL-2R) (P =0.037) as an independent predictive factor for CNS relapse (P=0.04, HR=7.02: 95%CI=1.87-26.22). Five of 9 CNS relapse patients were still alive with the combination treatment of whole brain irradiation, systemic chemotherapy (R- dexamethasone, cisplatin, cytarabine) and intrathecal chemotherapy. Conclusions: The incidence rate of CNS relapse in 137 DLBCL patients treated with R-CHOP, CEOP regimens may be lower than with CHOP in agreement with previous studies. Furthermore, rituximab may improve OS after CNS relapse. Ten times increased serum s-IL2R is a potential independent risk factor for CNS relapse and should be included in the IT prophylaxis indication in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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