Lymphoid and myeloid neoplasms involving cerebrospinal fluid: Comparison of morphologic examination and immunophenotyping by flow cytometry

Roma, Andres A.; Garcia, Alejandro J.; Avagnina, Alejandra; Rescia, Carla; Elsner, Boris

doi:10.1002/dc.10190

Cited by 71 publications

(54 citation statements)

References 20 publications

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“…15 Several reports have compared cytology with FC showing a broad range of concordant results. 4,9,10 Our FC findings and chimerism analysis in the group of patients relapsing in the CNS showed a high concordance degree. With the exception of three patients, agreement was observed between FC and chimerism analysis in 11 patients.…”

Section: Discussionsupporting

confidence: 61%

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Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Waterhouse

Bartsch

Bertz

et al. 2015

Bone Marrow Transplant

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Central nervous system (CNS) complications have been described in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Cerebrospinal fluid (CSF) analysis is included in the diagnostic workup in patients with neurological symptoms after alloHCT. CSF donor-recipient chimerism analysis usually is not used to evaluate patients with neurological complications after alloHCT. To assess the potential contribution of CSF donor-recipient chimerism in patients with neurological complications, we analyzed 85 CSF samples from 50 patients with neurological complications after alloHCT. After alloHCT, 21 patients showed the presence of recipient-derived DNA. In 13 of these patients, recurrence of the underlying disease was detected in CSF. There was a moderate correlation between the recipient DNA percentage as detected by short tandem repeat (STR) amplification and the cell concentration in CSF (Spearmann r: 0.66 P = 0.004). The percentage of cells with immunophenotypic abnormalities from patients relapsing in the CNS detected by flow cytometry showed a strong correlation with the percentage of recipient-derived DNA in CSF assessed by STR analysis (Spearmann r: 0.83 P = 0.0008). Donor-recipient chimerism analysis in CSF in patients with neurological symptoms after alloHCT is a practical, feasible and useful complementary method to the already established methodologies included in the diagnostic workup.Bone Marrow Transplantation (2016) 51, 127-131; doi:10.1038/bmt.2015; published online 5 October 2015 INTRODUCTIONNeurological complications after allogeneic hematopoietic cell transplantation (alloHCT) have been reported with a varying incidence between 8% and 42% in bone marrow recipients. 1 Among this type of complication, the incidence of central nervous system (CNS) relapse of the underlying disease ranged from 2.9% to 11% in patients undergoing alloHCT. 2 To begin a proper treatment as early as possible, an accurate and prompt diagnosis is mandatory. However, because of the several etiologies of neurological symptoms and the lack of optimal diagnostic methods, diagnosis could be challenging. In addition to neurological evaluation, several methods can be used to establish an accurate diagnosis.Cerebrospinal fluid (CSF) examination constitutes a part of the diagnostic work-up of patients with neurological symptoms after alloHCT. Cytological analysis is considered to be the gold standard for the detection of malignant cells in CSF. 3 However, cytology exhibits limitations regarding sensitivity and positive predictive value in the identification of malignant cells. Characterization of CSF cells using flow cytometry (FC) improved the detection of malignant and non-malignant cells and constitutes a useful diagnostic complement. 4 The reported use of molecular biology techniques in CSF cells in patients undergoing alloHCT is scarce, and these reports mostly refer to the pediatric population involving small patient cohorts. 5,6 Donor-recipient chimerism routinely used to evaluate hematopoietic chimerism foll...

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Section: Discussionsupporting

confidence: 61%

“…7,8 Furthermore, whereas several reports compare cytology with FC in the identification of CSF cells, there is no comparison between FC and chimerism analysis in this type of sample. 4,9,10 In this study, we evaluated the potential contribution of CSF donor-recipient chimerism analysis in patients with neurological symptoms following alloHCT. …”

mentioning

confidence: 99%

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Waterhouse

Bartsch

Bertz

et al. 2015

Bone Marrow Transplant

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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). 10,45,51 Patients with occult CNSL (i.e., CC-and FCM+ CSF) typically showed lower levels of CSF infiltration (<20% or <1 tumor B cell/μL) than FCM+/CC+ cases, 45 further supporting the greater sensitivity of FCM vs. CC.…”

Section: Multiparameter Flow Cytometry Analysis Of Csf Samplesmentioning

confidence: 88%

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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“…Although CSF analysis is essential for the management of intra-thecal treatment schedules, the diagnostic performance of either FCM or CM in the follow-up setting is mostly unknown [6,10,11]. Moreover, whether the two methods retain differential accuracy in different diagnostic subgroups is largely undetermined [2-4,6-9].…”

Section: Introductionmentioning

confidence: 99%

“…Cerebrospinal fluid (CSF) analysis by flow cytometry (FCM) and cytomorphology (CM) is currently requested to explore central nervous system (CNS) involvement by hematologic malignancy, both at diagnosis and during follow-up [1][2][3][4][5][6][7][8][9][10][11]. To date, the two methods have been mostly studied on CSF from newly diagnosed cases, i.e., those optimally evaluable samples not liable to intrathecal treatment-related damage [2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Flow cytometry and cytomorphology evaluation of hematologic malignancy in cerebrospinal fluids: comparison with retrospective clinical outcome

et al. 2011

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Lymphoid and myeloid neoplasms involving cerebrospinal fluid: Comparison of morphologic examination and immunophenotyping by flow cytometry

Cited by 71 publications

References 20 publications

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

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 cytometry and cytomorphology evaluation of hematologic malignancy in cerebrospinal fluids: comparison with retrospective clinical outcome

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