Clinical significance of occult cerebrospinal fluid involvement assessed by flow cytometry in non‐Hodgkin’s lymphoma patients at high risk of central nervous system disease in the rituximab era

Sancho, Juan‐Manuel; Órfão, Alberto; Quijano, Sandra; García, Olga; Panizo, Carlos; Pérez‐Ceballos, Elena; Debén, Guillermo; Salar, Antonio; González‐Barca, Eva; Alonso, Natalia; García‐Vela, Jose‐Antonio; Capote, Javier; Peñalver, Francisco‐Javier; Provencio, Mariano; Arias, Jesús; Plaza, J. M. Fernández; Caballero, Dolores; Morado, Marta; Feliú, Evarist; Ribera, Josep‐Marǐa

doi:10.1111/j.1600-0609.2010.01478.x

Cited by 53 publications

(52 citation statements)

References 36 publications

(57 reference statements)

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“…These results are consistent with several reports on the outcome of FCM+ CSF involvement in pooled analyses of aggressive B-cell lymphomas. 4,25,26 One small retrospective study showed an association between occult CSF involvement and risk of CNS relapse, and a second prospective study showed an adverse association between FCM + CSF and survival and risk of CNS progression. 25,26 The benefit of intrathecal therapy is controversial in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

“…4,25,26 One small retrospective study showed an association between occult CSF involvement and risk of CNS relapse, and a second prospective study showed an adverse association between FCM + CSF and survival and risk of CNS progression. 25,26 The benefit of intrathecal therapy is controversial in DLBCL. 9,13,24,27 The reasons for this controversy are multifactorial.…”

Section: Discussionmentioning

confidence: 99%

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Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

et al. 2014

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“…10,42,45,46 Early studies analyzing non-stabilized CSF samples by ≤4-color FCM already demonstrated increased sensitivity in between 3% and 20% of cases as compared with cytology (Table 2). 42,[47][48][49][50] More recent analyses of larger series of CSF-stabilized samples using 4-8 color FCM have confirmed the greater sensitivity of FCM vs. CC with a median proportion of occult CNSL (FCM+/CC-CSF) of 12% (range: 5%-13%) ( Table 1).…”

Section: Multiparameter Flow Cytometry Analysis Of Csf Samplesmentioning

confidence: 99%

Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)

et al. 2016

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Several factors hinder the identification of risk factors for central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL), including the retrospective nature of most studies, the relatively low frequency of CNS relapse in DLBCL, and the heterogeneity of CNS prophylaxis methods used in these studies. Moreover, the impact of newly developed diagnostic tools (such as multiparameter flow cytometry [FCM]) and new treatments introduced in the last decade, in particular rituximab, has still not been fully clarified.Several studies 4,5,[7][8][9][10] and a recent meta-analysis 1 have described a decrease in rates D iffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes, 1 and shortened overall survival of <6 months.2 Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system prophylaxis vs. therapy. [3][4][5] This report by the Spanish Lymphoma Group (GELTAMO) aims to provide useful guidelines and recommendations for the prevention, diagnosis, and treatment of central nervous system diffuse large B-cell lymphoma patients with, or at risk of, leptomeningeal and/or brain parenchyma lymphoma relapse. A panel of lymphoma experts working on behalf of GELTAMO reviewed all data published on these topics available in PubMed up to May 2016. Recommendations were classified according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach. 6 A practical algorithm based on the proposed recommendations was then developed (Figure 1 have concluded that the incidence of CNS relapse decreased after the introduction of rituximab (Table 1). The identification of risk factors has been the major goal of many studies of CNS involvement. Several large retrospective studies conducted in the pre-rituximab era [12][13][14][15] reported higher rates of CNS relapse in patients with increased serum lactate dehydrogenase (LDH) levels and/or involvement of >1 extranodal site, although these factors failed to predict CNS relapse in more than half of all cases.12 In addition to the involvement of >1 extranodal site and increased LDH, International Prognostic Index (IPI) score was also identified as an independent predictor for CNS relapse in other studies.13,16 A post-rituximab era study of 399 DLBCL patients, randomized to R-CHOP or CHOP chemotherapy, 3 identified an age-adjusted IPI (aaIPI) >1 as the only risk factor for CNS involvement, although a high aaIPI score was recorded for more than 60% of the patients. When aaIPI was excluded from the analysis, elevated LDH and a poor performance status (PS >1) were identified as independent predictive factors for CNS relapse. Similarly, in the randomized RICOVER-60 trial, 4 the combination of increased LDH levels, the involvement of >1 ex...

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“…Several studies comparing flow cytometry and conventional cytomorphology to detect CSF involvement in hematological malignancies (Table 2) describe samples in which flow cytometry is positive whilst cytology is negative (6,14,43,51). Presence of neurological symptoms compatible with leptomeningeal disease is highly suggestive for CNS involvement in such patients, whereas absence of symptoms and lack of recurrence of CNS disease during clinical follow-up indicate a falsepositive flow cytometric result (6,14).…”

Section: Sensitivity and Specificitymentioning

confidence: 99%

“…Results of clinical follow-up were documented in three studies. Sancho et al (51) found that a flow cytometry-positive, cytology-negative result was associated with a higher probability of CNS relapse in aggressive B-cell lymphomas, as compared to samples with absence of neoplastic cells by both methods, whereas Hegde et al (43) observed that 5/11 patients with a flow cytometry-positive, cytology-negative result relapsed in the clinical CNS and died despite having received active treatment. In addition, Bromberg et al (6) described the absence of CNS recurrence in only 1/24 flow cytometry-positive, cytology-negative patients.…”

Section: Sensitivity and Specificitymentioning

confidence: 99%

Flow cytometric characterization of cerebrospinal fluid cells

Graaf

Jongste

Kraan

et al. 2011

Cytometry Part B Clinical

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Flow cytometry facilitates the detection of a large spectrum of cellular characteristics on a per cell basis, determination of absolute cell numbers and detection of rare events with high sensitivity and specificity. White blood cell (WBC) counts in cerebrospinal fluid (CSF) are important for the diagnosis of many neurological disorders. WBC counting and differential can be performed by microscopy, hematology analyzers, or flow cytometry. Flow cytometry of CSF is increasingly being considered as the method of choice in patients suspected of leptomeningeal localization of hematological malignancies. Additionally, in several neuroinflammatory diseases such as multiple sclerosis and paraneoplastic neurological syndromes, flow cytometry is commonly performed to obtain insight into the immunopathogenesis of these diseases. Technically, the low cellularity of CSF samples, combined with the rapidly declining WBC viability, makes CSF flow cytometry challenging. Comparison of flow cytometry with microscopic and molecular techniques shows that each technique has its own advantages and is ideally combined. We expect that increasing the number of flow cytometric parameters that can be simultaneously studied within one sample, will further refine the information on CSF cell subsets in low-cellular CSF samples and enable to define cell populations more accurately. V C 2011 International Clinical Cytometry Society

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Clinical significance of occult cerebrospinal fluid involvement assessed by flow cytometry in non‐Hodgkin’s lymphoma patients at high risk of central nervous system disease in the rituximab era

Abstract: The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.

Cited by 53 publications

References 36 publications

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)

Flow cytometric characterization of cerebrospinal fluid cells

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