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

Cesana, Clara; Klersy, Catherine; Scarpati, Barbara; Brando, Bruno; Faleri, Maurizio; Bertani, Giambattista; Gatti, Arianna; Volpato, Elisabetta; Barba, Claudia; Ferri, Ursula; Scampini, Linda; Grillo, Giovanni; Lando, Giuliana; Nosari, Annamaria; Morra, Enrica; Cairoli, Roberto

doi:10.1007/s00277-010-1145-4

Cited by 18 publications

(24 citation statements)

References 20 publications

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“…CSF analysis includes cytomorphological examination in combination with immunocytochemistry . However, yield of tumor cells in CSF can be very low or tumor cells might be too lytic for proper analysis . Other parameters used for CSF analysis include clonality analysis by flow cytometry or immunoglobulin gene rearrangement analysis, as well as mutation analysis.…”

Section: Introductionmentioning

confidence: 99%

The use of droplet digital PCR in liquid biopsies: A highly sensitive technique for MYD88 p.(L265P) detection in cerebrospinal fluid

Hiemcke-Jiwa

Minnema

Loon

et al. 2017

Hematological Oncology

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The gold standard for diagnosis of central nervous system lymphomas still regards a stereotactic brain biopsy, with the risk of major complications for the patient. As tumor cells can be detected in cerebrospinal fluid (CSF), CSF analysis can be used as an alternative. In this respect, mutation analysis in CSF can be of added value to other diagnostic parameters such a cytomorphology and clonality analysis. A well-known example of targeted mutation analysis entails MYD88 p.(L265P) detection, which is present in the majority of Bing Neel syndrome and primary central nervous system lymphoma (PCNSL) patients. Unfortunately, tumor yield in CSF can be very low. Therefore, use of the highly sensitive droplet digital PCR (ddPCR) might be a suitable analysis strategy for targeted mutation detection. We analyzed 26 formalin fixed paraffin embedded (FFPE) samples (8 positive and 18 negative for MYD88 p.(L265P) mutation) by ddPCR, of which the results were compared with next generation sequencing (NGS). Subsequently, 32 CSF samples were analyzed by ddPCR. ddPCR and NGS results on FFPE material showed 100% concordance. Among the 32 CSF samples, 9 belonged to patients with lymphoplasmacytic lymphoma (LPL) and clinical suspicion of Bing Neel syndrome, and 3 belonged to patients with PCNSL. Nine of these samples tested positive for MYD88 p.(L265P) (8 LPL and 1 PCNSL). This study shows that sensitive MYD88 mutation analysis by ddPCR in CSF is highly reliable and can be applied even when DNA input is low. Therefore, ddPCR is of added value to current diagnostic parameters, especially when the available amount of DNA is limited.

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Section: Introductionmentioning

confidence: 99%

The use of droplet digital PCR in liquid biopsies: A highly sensitive technique for MYD88 p.(L265P) detection in cerebrospinal fluid

Hiemcke-Jiwa

Minnema

Loon

et al. 2017

Hematological Oncology

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“…A total of 41 studies comparing flow cytometry and cytology in CSF samples from patients with lymphoid neoplasia were identified .…”

Section: Resultsmentioning

confidence: 99%

“…: among these, 11 were excluded given they did not report complete results. [33][34][35][36][37][38][39][40][41][42][43] Additionally, three more articles were excluded given they contained significant numbers of myeloid malignancies which could not be excluded during data extraction (47 in Bromberg et al, 44 22 samples in Cesana et al, 45 8 cases in Kovach et al 46 ): their applicability to our research question was therefore considered too low to be included in this review.…”

Section: Resultsmentioning

confidence: 99%

Accuracy of flow cytometry and cytomorphology for the diagnosis of meningeal involvement in lymphoid neoplasms: A systematic review

Canovi

Campioli

2016

Diagnostic Cytopathology

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Central nervous system (CNS) involvement by lymphoid neoplasms is a relatively infrequent event that demands accurate identification. The purpose of this article is to review studies comparing diagnostic accuracy of flow cytometry (FCM) and cytomorphology (CM) for meningeal involvement from lymphoid neoplasms. Primary publications from the last 26 years were identified searching MedLine, Scopus, and Web of Science and systematically scanning bibliographies of identified articles. Only studies reporting complete results were included. We assessed study quality using the QUADAS‐2 tool. For each study, we extracted informations regarding study population, technical details about sample preparation, data analysis, and results. Twenty‐seven studies were included. A great heterogeneity regarding study populations and analytical procedures was observed among studies. Percentages of samples giving a positive result with both FCM and CM range from 0.3% to 42.9% among studies, whereas double negative samples go from 0% to 96.3%. Samples with positive FCM but negative CM are reported by 89% (24/27) of the studies with rates ranging from 3.5% to 61.5% of total specimens. On the contrary, samples with positive CM and negative FCM are found in 48% (13/27) of the studies with percentages ranging from 0.5% to 10%. Despite all the differences observed among studies, almost all of them state that employing flow cytometry along with conventional cytology increases the number of positive CSF samples for lymphoma involvement, although a few cases remain in whom only morphology can correctly identify malignant cells. Diagn. Cytopathol. 2016;44:841–856. © 2016 Wiley Periodicals, Inc.

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“…Treatment of CNS, either via CNS directed therapy given as a series of five weekly post-transplant lumbar punctures with the administration of intrathecal (IT) therapy (standard practice at JHH), or other post-transplant regimen or via pre-transplant CNS therapy has limited and unproved efficacy and may not help to prevent early relapse(25-27) When flow cytometric methods of disease detection in the CNS are used to improve the sensitivity of disease detections, it both improves upon accuracy of disease detection and can serve as a prognostic tool in outcomes in hematologic malignancies. (28-30) To further evaluate this, a biology study to look for evidence of pre-transplant minimal residual disease in the CNS by flow cytometry is being planned at our institution.…”

Section: Discussionmentioning

confidence: 99%

Factors Predictive of Relapse of Acute Leukemia in Children after Allogeneic Hematopoietic Cell Transplantation

Shah

Borowitz

Steinberg

et al. 2014

Biology of Blood and Marrow Transplantation

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The presence of minimal residual disease (MRD) pre-transplant is the most important prognostic risk factor predictive of post-transplant relapse in hematologic malignancies. However, MRD alone does not adequately predict relapse in all patients. To improve upon the ability to identify patients likely to relapse, we evaluated risk factors, in addition to MRD, which may be associated with development of post-transplant relapse. In this single institution, retrospective cohort study of children with acute leukemia or myelodysplastic syndrome who had undergone a first allogeneic transplant and had pre-transplant MRD evaluation, 40 of 93 patients (43%) experienced relapse. Univariate analysis demonstrated that African American race, high initial white blood cell count, central nervous system (CNS) disease at diagnosis, short first complete remission, non-myeloablative (NMA) conditioning, lack of remission and MRD pre-transplant were associated with worse relapse-free survival (RFS). In a Cox multivariable analysis, CNS disease (p=0.009), lack of remission (p=0.01) and NMA conditioning (p=0.04) were independently associated with inferior RFS. Amongst those in a morphologic complete remission who underwent a myeloablative transplant, having both CNS disease at diagnosis (specifically in acute lymphoblastic leukemia) and MRD positivity was an independent risk factor predictive of relapse, which has not been previously reported. Results from our study support the existence of risk factors complimentary to pre-transplant MRD. Validation in a larger independent homogenous cohort is needed to develop a prognostic tool for clinical use to predict post-transplant relapse.

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

Cited by 18 publications

References 20 publications

The use of droplet digital PCR in liquid biopsies: A highly sensitive technique for MYD88 p.(L265P) detection in cerebrospinal fluid

The use of droplet digital PCR in liquid biopsies: A highly sensitive technique for MYD88 p.(L265P) detection in cerebrospinal fluid

Accuracy of flow cytometry and cytomorphology for the diagnosis of meningeal involvement in lymphoid neoplasms: A systematic review

Factors Predictive of Relapse of Acute Leukemia in Children after Allogeneic Hematopoietic Cell Transplantation

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