The utility of flow cytometry for the detection of tumor cells in cerebrospinal fluid of patients with acute leukemia
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Mar 22, 2022
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Abstract
Central nervous system infiltration by acute leukemia is a poor prognosis variable, and conventional cytology is the gold standard for its diagnosis; the technique is highly specific but not sensitive. To improve the diagnosis, flow cytometry has been used in different studies, showing greater sensitivity in the detection of leukemic cells. This study aimed to evaluate the presence of tumor cells by flow
cytometry and conventional cytology, in cerebrospinal fluid from patients with acute leukemia as well as its relationship with clinical and biological parameters. In total, 156 CSF samples from 55 children with acute leukemia were studied. We found the following results: FCM-/CC- 131/156; FCM+/CC- 19/156; FCM-/CC+ 0; FCM+/CC+ 1/156; FC-/CC suspicious 1/156; and FCM+/CC suspicious 4/156. Patients with B-cell acute lymphoblastic leukemia and FCM+ showed a lower response to steroid-treatment, abnormal karyotype, neurological symptoms, and worse relapsefree survival. Patients with T-cell acute lymphoblastic leukemia and FCM+ demonstrated association with thrombocytopenia. In conclusion, flow cytometry has greater sensitivity for the detection of tumor infiltration in cerebrospinal fluid, a finding that correlates with prognostic parameters in patients with acute leukemia.
Keywords
Acute leukemia, CNS infiltration, flow cytometry, conventional cytology
References
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doi: 10.1111/j.1365-4592257.2006.00741.x
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doi: 10.1007/s00277-010-1145-4
[23] Cancela CSP, Murao M, Souza ME de L, Barcelos JM, Furtado VM; Silva ML, Viana MB, de Oliveira BM. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping. Jornal Brasileiro de Patologia eMedicina Laboratorial.
49(4): 260–263, 2013.
doi: 10.1590/S1676-24442013000400005
[24] Crespo-Solis E, López-Karpovitch X, Higuera J, Vega-Ramos B. Diagnosis of acute leukemia in cerebrospinal fluid (CSF-Acute Leukemia). Current Oncology Reports. 14(5): 369–378. 468, 2012.
doi: 10.1007/s11912-012-0248-6
[25] de Graaf MT, de Jongste AHC, Kraan J, Boonstra JG, Smitt PAES, Gratama JW. Flow cytometric characterization of cerebrospinal fluid cells. Cytometry Part B: Clinical Cytometry. 80B(5): 271–281, 2011.
doi: 10.1002/cyto.b.20603
[26] Subirá D, Castañón S, Román A, et al. Flow cytometry and the study of central nervous disease in patients with acute leukemia. British Journal of Haematology.112(2): 381–384, 2001.
doi: 10.1046/j.1365-2141.2001.02505.x
[27] Kleine TO, Benes L. Immune surveillance of the human central nervous system (CNS): Different migration pathways of immune cells through the blood-brain barrier and bloodcerebrospinal fluid barrier in healthy persons. Cytometry Part A. 69(3): 147–151, 2006.
doi: 10.1002/cyto.a.20225
[28] Hanahan D and Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 144: 646–674, 2011.
doi: 10.1016/j.cell.2011.02.013
[29] Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukemia. The Lancet Oncology. 9(3): 257–268, 2008.
doi: 10.1016/S1470-4832045(08)70070-6
[30] Akers SM, Rellick SL, Fortney JE, Gibson LF. Cellular elements of the subarachnoid space promote ALL survival during chemotherapy. Leukemia Research. 35(6): 705–711, 2011
doi: 10.1016/j.leukres.2010.12.031
[31] Nolan C, Deangelis LM. Overview of metastatic disease of the central nervous system. Handbook of Clinical Neurology. 2018(149): 3–23.
doi: 10.1016/B978-0-12-811161-1.00001-3
doi: 10.1053/j.seminoncol.2009.05.002
[2] Pui CH. Central nervous system disease in acute lymphoblastic leukemia: prophylaxis and treatment, American Society of Hematology. 2006(1): 142–146, 2006.
doi: 10.1182/asheducation-2006.1.142
[3] Colocci N, Glantz M, Recht L. Prevention and treatment of central nervous system involvement by non-Hodgkin’s lymphoma: a review of the literature. Seminars in Neurology. 24(4): 395–404, 2004.
doi: 10.1055/s-2004-861534
[4] Glantz MJ, Cole BF, Glantz LK, Cobb J, Mills P, Lekos A, Walters B, Recht L. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer. 82(4): 733–739, 1998.
doi: 10.1002/(sici)1097-0142(19980215)82:4<733::aid-cncr17>3.0.co;2-z
[5] Glass JP, Melamed M, Chernik NL PJB. Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology. 29(10): 1369–1375, 1979.
doi: 10.1212/wnl.29.10.1369
[6] Chamberlain MC. Neoplastic Meningitis. The Oncologist. 13(9): 967–977, 2008.
doi: 10.1634/theoncologist.2008-0138402
[7] del Principe MI, Buccisano F, Cefalo M, Maurillo L, Di Caprio L, Di Piazza F, Sarlo C, De Angelis G, Consalvo MI, Fraboni D, De Santis G, Ditto C, Postorino M, Sconocchia G, Del Poeta G, Amadori S, Venditti A. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma. Annals of Hematology. 93(9): 1509–1513. 405, 2014.
doi: 10.1007/s00277-014-2080-6
[8] Martínez-Laperche C, Gómez-García AM, Lassaletta Á, Moscardó C, Vivanco JL, Molina J, Fuster J, Couselo JM, Sánchez de Toledo J, Bureo E, Madero L, Ramirez M. Detection of occult cerebrospinal fluid involvement during maintenance therapy identifies a group of
children with acute lymphoblastic leukemia at high risk for relapse. American Journal of Hematology. 88(5): 359–364, 2013.
doi: 10.1002/ajh.23407
[9] Quijano S, López A, Sancho JM, Panizo C, Guillermo Debén G, Castilla C, García-Vela JA, Salar A, Alonso-Vence N, González-Barca E, Peñalver FJ, Plaza-Villa J, Morado M, García-Marco J, Arias J, Briones J, Ferrer S, Capote J, Nicolás C, Orfao A. Identification of leptomeningeal disease in aggressive B-Cell non-Hodgkin’s lymphoma: Improved sensitivity of flow cytometry. Journal of Clinical Oncology. 27(9): 1462–1469, 2009.
doi: 10.1200/JCO.2008.17.7089
[10] Sancho JM, Orfao A, Quijano S, García O, Panizo C, Pérez-Ceballos E, Deben G, Salar A, González-Barca E, Alonso N, García-Vela JA, Capote J, Peñalver FJ, Provencio M, Arias J, Plaza J, Caballero D, Morado M, Feliu E, Ribera JM. 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. European Journal of Haematology. 85(4): 321–328, 2010.
doi: 10.1111/j.1600-0609.2010.01478.x
[11] Ranta S, Nilsson F, Harila-Saari A, Saft L, Tani E, Soderhall S, Porwit A, Hultdin M, Noren-Nystrom U, Heyman M. Detection of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia by Cytomorphology and Flow Cytometry of the Cerebrospinal Fluid. Pediatric Blood Cancer. 62(6): 951–956, 2014.
doi: 10.1002/pbc.25363
[12] de Jongste AH, Kraan J, van den Broek PD, Brooimans RA, Bromberg JE, van Montfort KA, Sillevis Smitt PA, Gratama JW. Use of TransFixTM cerebrospinal fluid storage tubes prevents cellular loss and enhances flow cytometric detection of malignant hematological cells after 18 hours of storage. Cytometry Part B – Clinical Cytometry. 86(4): 272–279, 2014.
doi: 10.1002/cyto.b.21097
[13] Kraan J, Gratama JW, Haioun C, Orfao A, Plonquet A, Porwit A, Quijano S, Stetler-Stevenson M, Wilson W. Flow Cytometric Immunophenotyping of Cerebrospinal Fluid. Current Protocols in Cytometry. Unit 6.25: 4–19, 2008.
doi: 10.1002/0471142956.cy0101s39
[14] van Dongen JJM, Lhermitte L, Bottcher S, Almeida J, van der Velden VHJ, Flores-Montero J, Rawstron A, Asnafi V, Lecrevisse Q, Lucio P, Mejstrikova E, Szczepanski T, Kalina T, de Tute R, Bruggemann M, Sedek L, Cullen M, Langerak AW, Mendonca A, Macintyre
E, Martin-Ayuso M, Hrusak O, Vidriales MB, Orfao A. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 26(9): 1908–1975, 2012.
doi: 10.1038/leu.2012.120
[15] Pui CH, Robison LL, Look AT. Acute Lymphoblastic Leukaemia. Lancet. 371: 1030–1043, 2008.
doi: 10.1016/S0140-6736(08)60457-2
[16] Sayed D, Badrawy H, Ali AM, Shaker S. Immunophenotyping and immunoglobulin heavy chain gene rearrangement analysis in cerebrospinal fluid of pediatric patients with acute lymphoblastic leukemia. Leukemia Research. 33(5): 655–661, 2009.
doi: 10.1016/j.leukres.2008.09.033
[17] di Noto R, Scalia G, Abate G, Gorrese M, Pascariello C, Raia M, Morabito P, Capone F, Lo Pardo C, Mirabelli P, Mariotti E, Del Vecchio L. Critical role of multidimensional flow cytometry in detecting occult leptomeningeal disease in newly diagnosed aggressive B-cell
lymphomas. Leukemia Research. 32(8): 1196–1199, 2008.
doi: 10.1016/j.leukres.2007.12.016
[18] Popov A, Henze G, Verzhbitskaya T, Roumiantseva J, Lagoyko S, Khlebnikova O, Streneva O, Bidanov O, Tsaur G, Inaba H, Karachunskiy A, Fechina L. Absolute count of leukemic blasts in cerebrospinal fluid as detected by flow cytometry is a relevant prognostic factor in children with acute lymphoblastic leukemia. Journal of Cancer Research and Clinical Oncology. 145: 1331–1339, 2019.
doi: 10.1007/s00432-019-02886-3
[19] Gong X, Lin D, Wang H, Wang Y, Liu B, Wei H, Zhou C, Liu K, Wei S, Gong B, Zhang G, Liu Y, Zhao X, Li Y, Gu R, Qiu S, Mi JW. Flow Cytometric Analysis of Cerebrospinal Fluid in Adult Patients with Acute Lymphoblastic Leukemia during Follow-Up. European
Journal of Haematology. 100(3): 279–285, 2018.
doi: 10.1111/ijlh.12426
[20] del Principe MI, Buccisano F, Soddu S, Maurillo L, Cefalo M, Piciocchi A, Consalvo MI, Paterno G, Sarlo C, De Bellis E, Zizzari A, De Angelis G, Fraboni D, Divona M, Voso MT, Sconocchia G, Del Poeta G, Lo-Coco F, Arcese W, Amadori S, Venditti A. Involvement of
central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome. Seminars in Hematology. 55(4): 209–214, 2018.
doi: 10.1053/j.seminhematol.2018.02.006
[21] Nückel H, Novotny JR, Noppeney R, Savidou I, Dührsen U. Detection of malignant haematopoietic cells in the cerebrospinal fluid by conventional cytology and flow cytometry. Clinical and Laboratory Haematology. 28(1): 22–29, 2006.
doi: 10.1111/j.1365-4592257.2006.00741.x
[22] Cesana C, Klersy C, Scarpati B, Brando B, Faleri M, Bertani G, Gatti A, Volpato E, Barba C, Ferri U, Scampini L, Grillo G, Lando G, Nosari A, Morra E, Cairoli R. Flow cytometry and cytomorphology evaluation of hematologic malignancy in cerebrospinal fluids: Comparison with retrospective clinical outcome. Annals of Hematology. 90(7): 827–835, 2011.
doi: 10.1007/s00277-010-1145-4
[23] Cancela CSP, Murao M, Souza ME de L, Barcelos JM, Furtado VM; Silva ML, Viana MB, de Oliveira BM. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping. Jornal Brasileiro de Patologia eMedicina Laboratorial.
49(4): 260–263, 2013.
doi: 10.1590/S1676-24442013000400005
[24] Crespo-Solis E, López-Karpovitch X, Higuera J, Vega-Ramos B. Diagnosis of acute leukemia in cerebrospinal fluid (CSF-Acute Leukemia). Current Oncology Reports. 14(5): 369–378. 468, 2012.
doi: 10.1007/s11912-012-0248-6
[25] de Graaf MT, de Jongste AHC, Kraan J, Boonstra JG, Smitt PAES, Gratama JW. Flow cytometric characterization of cerebrospinal fluid cells. Cytometry Part B: Clinical Cytometry. 80B(5): 271–281, 2011.
doi: 10.1002/cyto.b.20603
[26] Subirá D, Castañón S, Román A, et al. Flow cytometry and the study of central nervous disease in patients with acute leukemia. British Journal of Haematology.112(2): 381–384, 2001.
doi: 10.1046/j.1365-2141.2001.02505.x
[27] Kleine TO, Benes L. Immune surveillance of the human central nervous system (CNS): Different migration pathways of immune cells through the blood-brain barrier and bloodcerebrospinal fluid barrier in healthy persons. Cytometry Part A. 69(3): 147–151, 2006.
doi: 10.1002/cyto.a.20225
[28] Hanahan D and Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell. 144: 646–674, 2011.
doi: 10.1016/j.cell.2011.02.013
[29] Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukemia. The Lancet Oncology. 9(3): 257–268, 2008.
doi: 10.1016/S1470-4832045(08)70070-6
[30] Akers SM, Rellick SL, Fortney JE, Gibson LF. Cellular elements of the subarachnoid space promote ALL survival during chemotherapy. Leukemia Research. 35(6): 705–711, 2011
doi: 10.1016/j.leukres.2010.12.031
[31] Nolan C, Deangelis LM. Overview of metastatic disease of the central nervous system. Handbook of Clinical Neurology. 2018(149): 3–23.
doi: 10.1016/B978-0-12-811161-1.00001-3
How to Cite
Torres, X., De Los Reyes, I., Vizcaíno, M., Guzmán, P. C., Campos, A., Peñalosa, N., Uribe, A. M., Saavedra, C., Romero, M., Cuéllar, G., Martin, L., Rodriguez, P., Cardozo, C., & Quijano, S. (2022). The utility of flow cytometry for the detection of tumor cells in cerebrospinal fluid of patients with acute leukemia. Universitas Scientiarum, 27(1), 15–32. https://doi.org/10.11144/Javeriana.SC271.tuof
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