Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era

Bay-area Lymphoma Information Network, Tokyo, Japan.
Cancer Science (Impact Factor: 3.52). 11/2011; 103(2):245-51. DOI: 10.1111/j.1349-7006.2011.02139.x
Source: PubMed


Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further.

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Available from: Rishu Takimoto, Sep 22, 2014
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    • "Sato et al (20) reviewed 14 lymphoma cases presenting with ONP, and ten out of 14 were assessed by using brain MRI, which detected eight patients with CNS involvement. The majority of the patients with pupil-sparing ONP exhibited cavernous sinus involvement rather than oculomotor nerve infiltration (16). Brain MRI combined with cerebrospinal fluid (CSF) cytology examination is considered optimal for evaluating the cause of ONP, but may not be diagnostic in every case. "
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    ABSTRACT: Isolated oculomotor nerve palsy (ONP) is rare. The major causes are aneurysm of the posterior communicating artery, microvascular ischemia, neoplasm, inflammation and trauma. The present study reports the case of a 72-year-old female with left isolated pupil-sparing ONP and severe anemia as the initial manifestations of gastric diffuse large B-cell lymphoma (DLBCL). Systemic chemotherapy without any central nervous system (CNS)-directed treatment led to a complete resolution of the ONP, suggesting that it was most likely to be a paraneoplastic phenomenon. If CNS involvement cannot be demonstrated by brain magnetic resonance imaging and cerebrospinal fluid assessment, the present case suggests that it may be acceptable to omit CNS-directed therapy in such cases of ONP, since it may be paraneoplastic in nature and may resolve following successful treatment of the underlying malignancy.
    Full-text · Article · Nov 2014 · Oncology letters
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    • "Patients were selected for CNS prophylaxis strategies by their primary managing haematologist if they fulfilled two or more of the following criteria: (1) multiple extranodal sites; (2) elevated serum LDH; (3) or B symptoms. In addition, involvement of specific high-risk anatomical sites, that is, bone marrow (with large cell lymphoma) (Bos et al, 1998), breast (Ryan et al, 2006), testis (Zucca et al, 2003), kidney (Villa et al, 2010), adrenal glands (Tomita et al, 2012), paranasal sinus, nasopharynx, liver and paravertebral (Ferreri et al, 2009) was also considered an indication for CNS prophylaxis. The features of patients by treatment groups are summarised in Table 1. "
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    ABSTRACT: Background: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. Methods: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP ‘group 1' R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX ‘group 2' dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX ‘group 3'. Results: Overall, 217 patients were identified (49, 125 and 43 in groups 1–3, respectively). With median follow-up of 3.4 (range 0.2–18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1–3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5–33.1%), 6.9% (3.5–13.4%) and 2.3% (0.4–15.4%) in groups 1–3, respectively (P=0.009). Conclusions: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.
    Full-text · Article · Jul 2014 · British Journal of Cancer
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    • "In Case 4, cerebral and adrenal lesions were detected simultaneously. It is reported that DLBCL with adrenal involvement could have a tendency to develop CNS infiltration [15], so we think that simultaneous involvement of CNS and adrenal glands by lymphoma would be considered as PAL with secondary CNS involvement, as Rashidi A et al. recently stated [16]. "
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    ABSTRACT: Primary adrenal lymphoma (PAL) is an extremely rare subtype of extranodal non-Hodgkin's lymphoma. Some researchers have reported some of the characteristics of PAL and its association with poor prognosis; however, the clinicopathological features of PAL remain to be elucidated. From 2008 to 2011 we experienced seven cases of PAL in our institutions. We retrospectively analyzed the clinical and pathological features of these patients. The patients ranged in age from 50 to 85 years, with a median of 71 years. The overall male:female ratio was 6:1. All seven patients were diagnosed with diffuse large B-cell lymphoma (DLBCL) pathologically. Bilateral adrenal involvement was confirmed in five patients. The median largest tumor diameter at diagnosis was 58 mm. The Ki-67 index was generally high (>70%). All patients were treated with rituximab-containing chemotherapy, and central nervous system (CNS) prophylaxis was conducted for three patients. One patient with CNS involvement at the time of the diagnosis also received whole-brain radiation. The overall survival rate at two years was 57% (median follow-up; 24.8 months). It is noteworthy that the three patients who received a full course of the rituximab-containing regimen and CNS prophylaxis are currently alive without disease relapse, and that none of the seven patients died due to progression of lymphoma. Primary adrenal DLBCL can be a clinically aggressive disease entity. Rituximab-containing chemotherapy combined with CNS prophylaxis could be a reasonable option for the treatment of PAL; however, analyses of more PAL cases are needed for the establishment of this strategy.
    Full-text · Article · Aug 2013
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