Impacto da detecção de blastos leucêmicos durante o protocolo de tratamento dos pacientes pediátricos com leucemia linfoblástica aguda de células b: implicações clínicas elaboratoriais

dc.contributor.advisorCosta, Allyson Guimarães da
dc.contributor.advisor-latteshttp://lattes.cnpq.br/7531662673281014
dc.contributor.authorCatão, Claudio Lucas dos Santos
dc.contributor.author-latteshttp://lattes.cnpq.br/3925752009134903
dc.contributor.co-advisorPassos, Leny Nascimento da Motta
dc.contributor.co-advisor-latteshttp://lattes.cnpq.br/8194622149198642
dc.contributor.referee1Costa, Allyson Guimarães da
dc.contributor.referee1Latteshttp://lattes.cnpq.br/7531662673281014
dc.contributor.referee2Araújo, Nilberto Dias de
dc.contributor.referee2Latteshttp://lattes.cnpq.br/2649009048520935
dc.contributor.referee3Pontes, Letícia Gomes
dc.contributor.referee3Latteshttp://lattes.cnpq.br/8116355457327399
dc.date.accessioned2026-01-13T14:08:01Z
dc.date.issued2024-08-28
dc.description.abstractMeasurable residual disease (MRD) is the most important independent predictor of relapse risk and long-term survival in children with B-cell acute lymphoblastic leukemia (B-ALL), defined as the detection and/or quantification of residual leukemic blasts beyond the sensitivity level of cytomorphology, i.e., by more sensitive methodologies such as flow cytometry or molecular methods. Negative MRD is considered, to a variable extent and according to the technique adopted, as <0.01 to 0.1% of leukemic blasts in the bone marrow (BM). Based on this result, it is possible to optimize chemotherapy, minimizing toxicity and reducing the risk of relapse. Thus, our study described the clinical and laboratory implications after the identification of leukemic blasts during the treatment protocol of pediatric patients with B-ALL. A longitudinal, prospective, analytical study was conducted to evaluate bone marrow (BM) and peripheral blood (PB) samples from pediatric patients undergoing remission induction therapy for B-ALL at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) for evaluation of MRD by flow cytometry (FC). The protocols and guidelines of the EuroFlow Consortium were used, with the acquisition of samples on the FACSCanto II cytometer of the HEMOAM Foundation and the analysis of immunophenotyping data with the Kaluza software (v1.2). In parallel, sociodemographic and clinical-laboratory data were collected from the iDoctor System, physical records of patients and the SofLab system. Twenty- five patients diagnosed with B-ALL at an average age of 6 years, predominantly female (68%), were included in the study. The individuals were evaluated and started treatment with the BFM-2009 protocol, being classified into high-risk (40%), intermediate-risk (32%), and low-risk (28%) groups. When comparing the techniques adopted by the routine with flow cytometry analysis using the protocol adapted from the EuroFlow Consortium, it was noted that there was significantly greater acquisition and evaluation of cells by the method described in our study. When comparing the detection of LCs, we observed that our protocol (adapted from the EuroFlow Consortium) was significantly better in detecting blasts at times D15, D35, and D84. Although no significant differences were observed at D8, it was noted that the FC was relatively better than the automated count. In conclusion, we can see that our study indicated better results regarding the early detection of leukemic blasts and the evaluation of MRD during chemotherapy treatment, with a positive impact on the patients' prognosis.
dc.description.resumoMeasurable residual disease (MRD) is the most important independent predictor of relapse risk and long-term survival in children with B-cell acute lymphoblastic leukemia (B-ALL), defined as the detection and/or quantification of residual leukemic blasts beyond the sensitivity level of cytomorphology, i.e., by more sensitive methodologies such as flow cytometry or molecular methods. Negative MRD is considered, to a variable extent and according to the technique adopted, as <0.01 to 0.1% of leukemic blasts in the bone marrow (BM). Based on this result, it is possible to optimize chemotherapy, minimizing toxicity and reducing the risk of relapse. Thus, our study described the clinical and laboratory implications after the identification of leukemic blasts during the treatment protocol of pediatric patients with B-ALL. A longitudinal, prospective, analytical study was conducted to evaluate bone marrow (BM) and peripheral blood (PB) samples from pediatric patients undergoing remission induction therapy for B-ALL at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) for evaluation of MRD by flow cytometry (FC). The protocols and guidelines of the EuroFlow Consortium were used, with the acquisition of samples on the FACSCanto II cytometer of the HEMOAM Foundation and the analysis of immunophenotyping data with the Kaluza software (v1.2). In parallel, sociodemographic and clinical-laboratory data were collected from the iDoctor System, physical records of patients and the SofLab system. Twenty- five patients diagnosed with B-ALL at an average age of 6 years, predominantly female (68%), were included in the study. The individuals were evaluated and started treatment with the BFM-2009 protocol, being classified into high-risk (40%), intermediate-risk (32%), and low-risk (28%) groups. When comparing the techniques adopted by the routine with flow cytometry analysis using the protocol adapted from the EuroFlow Consortium, it was noted that there was significantly greater acquisition and evaluation of cells by the method described in our study. When comparing the detection of LCs, we observed that our protocol (adapted from the EuroFlow Consortium) was significantly better in detecting blasts at times D15, D35, and D84. Although no significant differences were observed at D8, it was noted that the FC was relatively better than the automated count. In conclusion, we can see that our study indicated better results regarding the early detection of leukemic blasts and the evaluation of MRD during chemotherapy treatment, with a positive impact on the patients' prognosis.
dc.description.sponsorshipA Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.identifier.citationCATÃO, Claudio Lucas dos Santos. Impacto da detecção de blastos leucêmicos durante o protocolo de tratamento dos pacientes pediátricos com leucemia linfoblástica aguda de células b: implicações clínicas elaboratoriais. (Dissertação) Mestrado em Ciências Apricadas à Hematologia). Manaus, UEA, 2025
dc.identifier.urihttps://ri.uea.edu.br/handle/riuea/8017
dc.publisherUniversidade do Estado do Amazonas
dc.publisher.initialsUEA
dc.publisher.programPrograma de Pós-Graduação em Ciências Aplicadas à Hematologia
dc.relation.references1. Kruse A, Abdel-Azim N, Kim HN, Ruan Y, Phan V, Ogana H, Wang W, Lee R, Gang EJ, Khazal S, et al. Minimal residual disease detection in acute lymphoblastic leukemia. Int J Mol Sci (2020) 21: doi: 10.3390/ijms21031054 2. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J (2017) 7:e577. doi: 10.1038/bcj.2017.53 3. DiGiuseppe JA, Wood BL. Applications of Flow Cytometric Immunophenotyping in the Diagnosis and Posttreatment Monitoring of B and T Lymphoblastic Leukemia/Lymphoma. Cytometry B Clin Cytom (2019) 96:256–265. doi: 10.1002/cyto.b.21833 4. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J (2017) 7:e577. doi: 10.1038/bcj.2017.53 5. Da Costa Salina TD, Ferreira YA, Alves EB, Ferreira CM, De Paula EV, Mira MT, Da Mota Passos L. Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia. Sci Rep (2016) 6:6–11. doi: 10.1038/srep31179 6. Simioni C, Conti I, Varano G, Brenna C, Costanzi E, Neri LM. The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia : Implications for Therapies. (2021) 11:1–14. doi: 10.3389/fonc.2021.673506 7. Rocha JMC, Xavier SG, de Lima Souza ME, Assumpção JG, Murao M, de Oliveira BM. Current strategies for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis (2016) 8: doi: 10.4084/MJHID.2016.024 8. Roberts I, Fordham NJ, Rao A, Bain BJ. Neonatal leukaemia. Br J Haematol (2018) 182:170–184. doi: 10.1111/bjh.15246 9. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Blood (2009) 114:937–951. doi: 10.1182/blood-2009-03-209262 10. Chiarini F, Lonetti A, Evangelisti C, Buontempo F, Orsini E, Evangelisti C, Cappellini A, Neri LM, McCubrey JA, Martelli AM. Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting. Biochim Biophys Acta Mol Cell Res (2016) 1863:449–463. doi: 10.1016/j.bbamcr.2015.08.015 11. Pedrosa F, Lins M. Leucemia linfóide aguda: uma doença curável Acute lymphoblastic leukemia: a curable disease. Rev bras saúde matern infant (2002) 2:63–68. 12. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. The Lancet (2013) 381:1943–1955. doi: 10.1016/S0140-6736(12)62187-4 62 13. Venturi V, Masek T, Pospišek M. A blood pact: The significance and implications of eIF4E on lymphocytic leukemia. Physiol Res (2018) 67:363–382. doi: 10.33549/physiolres.933696 14. Dumont dUrville J-S-C, DOrbigny AD, Eyries JBB, Jacobs A. Leucemia linfoblástica aguda. Histoire Générale des Voyages (2015)593–597. doi: 10.1017/cbo9781139107563.069 15. Rashighi M, Harris JE. Clonal Hematopoiesis in Cancer. HHS Public Access (2020) 176:139–148. doi: 10.1053/j.gastro.2016.08.014.CagY 16. Azizidoost S, Babashah S, Rahim F, Shahjahani M, Saki N. Bone marrow neoplastic niche in leukemia. Hematology (2014) 19:232–238. doi: 10.1179/1607845413Y.0000000111 17. Greaves M. Childhood Leukemia. Abeloff’s Clinical Oncology (2002) 324:1748- 1764.e4. doi: 10.1016/B978-0-323-47674-4.00093-1 18. Fujita TC, Sousa-Pereira N, Amarante MK, Watanabe MAE. Acute lymphoid leukemia etiopathogenesis. Mol Biol Rep (2021) 48:817–822. doi: 10.1007/s11033-020-06073-3 19. Rafei H, Kantarjian HM, Jabbour EJ. Recent advances in the treatment of acute lymphoblastic leukemia. Leuk Lymphoma (2019) 60:2606–2621. doi: 10.1080/10428194.2019.1605071 20. Moreira LA, Batista SC, Beira J. Diagnóstico de Leucemias linfóides agudas : Uma Revisão. Saúde em Foco (2018) 10:279–87. 21. Jeffrey S. Chang, Mi Zhou, Patricia A. Buffler, Anand P. Chokkalingam C, Metayer and JLW. Profound deficit of IL10 at birth in children who develop childhood acute lymphoblastic leukemia. NIH (2012) 23:1–7. doi: 10.1158/1055- 9965.EPI-11-0162.Profound 22. A.F.Vieira, B. Neves, S.R.Tonelli. Perfil Epidemiológico Da Leucemia Linfoide Nas Regiões Do Brasil Epidemiological Profile of Lymphoid Leukemia in Brazil Region. (2017) 55:130–143. 23. Whiteley AE, Price TT, Cantelli G, Sipkins DA. Leukaemia: a model metastatic disease. Nat Rev Cancer (2021) 21:461–475. doi: 10.1038/s41568-021-00355-z 24. Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F, Hesseling P, Shin HY, Stiller CA, Bouzbid S, et al. International incidence of childhood cancer, 2001–10: a population-based registry study. Lancet Oncol (2017) 18:719–731. doi: 10.1016/S1470-2045(17)30186-9 25. INCA. Estimativa 2023 : incidência de câncer no Brasil / Instituto Nacional de Câncer. (2022). 26. ALENCAR GOMES DA SILVA. Estimativa | 2020 Incidência de Câncer no Brasil. (2557). 88–100 p. 27. Chan KW. Acute Lymphoblastic Leukemia Biologic Features of ALL Morphologic and Cytochemical Classification. Curr Probl Pediatr (2002) 32:40– 49. 63 28. Silva AL, Alves FS, Kerr MWA, Xabregas LA, Gama FM, Rodrigues MGA, Torres AS, Tarragô AM, Sampaio VS, Carvalho MPSS, et al. Acute lymphoid and myeloid leukemia in a Brazilian Amazon population: Epidemiology and predictors of comorbidity and deaths. PLoS One (2019) 14:1–16. doi: 10.1371/journal.pone.0221518 29. Ries L, Trama A, Nakata K, Gatta G, Botta L, Bleyer A. Cancer Incidence, Survival, and Mortality Among Adolescents and Young Adults. Pediatric Oncology (2017) 38:7–42. doi: 10.1007/978-3-319-33679-4_2 30. Mikosik A, Henc I, Ruckemann-Dziurdzińska K, Frckowiak JE, Płoszyńska A, Balcerska A, Bryl E, Witkowski JM. Increased μ-calpain activity in blasts of common B-precursor childhood acute lymphoblastic leukemia correlates with their lower susceptibility to apoptosis. PLoS One (2015) 10:1–16. doi: 10.1371/journal.pone.0136615 31. Rose-Inman H, Kuehl D. Acute Leukemia. Hematol Oncol Clin North Am (2017) 31:1011–1028. doi: 10.1016/j.hoc.2017.08.006 32. American Cancer Society. Acute Lymphocytic Leukemia Early Detection, Diagnosis and Types. American Cancer Society (2018)1–21. 33. Brunning RD, Because •. Classification of Acute Leukemias. (2003) doi: 10.1053/s0740-2570(03)00031-5 34. Devitt KA, Oldaker T, Shah K, Illingworth A. Summary of validation considerations with real-life examples using both qualitative and semiquantitative flow cytometry assays. Cytometry B Clin Cytom (2023)1–18. doi: 10.1002/cyto.b.22123 35. Da Silva GC, Pilger DA, De Castro SM, Wagner SC. Diagnóstico laboratorial das leucemias mielóides agudas. J Bras Patol Med Lab (2006) 42:77–84. doi: 10.1590/S1676-24442006000200004 36. Arber DA, Orazi A, Hasserjian R. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia (Blood (2016) 127, 20 (2391-2405)). Blood (2016) 128:462–463. doi: 10.1182/blood- 2016-06-721662 37. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IB de O, Berti E, Bhagat G, Borges AM, Boyer D, Calaminici M, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia (2022) 36:1720–1748. doi: 10.1038/s41375-022-01620-2 38. Porwit A, Béné MC. Multiparameter flow cytometry applications in the diagnosis of mixed phenotype acute leukemia. Cytometry B Clin Cytom (2019) 96:183–194. doi: 10.1002/cyto.b.21783 39. Schroeder HW, Radbruch A, Berek C. B-Cell Development and Differentiation. Fifth Edit. Elsevier Ltd (2019). 107-118.e1 p. doi: 10.1016/B978-0-7020-6896- 6.00007-7 40. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatrics International (2018) 60:4–12. doi: 10.1111/ped.13457 64 41. Caner Saygin, Joseph Cannova WS and LM. Measurable Residual Disease in Acute Lymphoblastic Leukemia: Techniques and Therapeutic Utility. Clinical Advances in Hematology and Oncology (2022) 20:419–421. 42. Kumar A, Taghi Khani A, Duault C, Aramburo S, Sanchez Ortiz A, Lee SJ, Chan A, McDonald T, Huang M, Lacayo NJ, et al. Intrinsic suppression of type i interferon production underlies the therapeutic efficacy of IL-15-producing natural killer cells in B-cell acute lymphoblastic leukemia. J Immunother Cancer (2023) 11: doi: 10.1136/jitc-2022-006649 43. Pierro J, Hogan LE, Bhatla T, Carroll WL, Brook S. New Targeted Therapies for Relapsed Pediatric Lymphoblastic Leukemia. HHS Public Access (2018) 17:725– 736. doi: 10.1080/14737140.2017.1347507.New 44. Magalhães-Gama F, Kerr MWA, De Araújo ND, Ibiapina HNS, Neves JCF, Hanna FSA, Xabregas LDA, Carvalho MPSS, Alves EB, Tarragô AM, et al. Imbalance of Chemokines and Cytokines in the Bone Marrow Microenvironment of Children with B-Cell Acute Lymphoblastic Leukemia. J Oncol (2021) 2021: doi: 10.1155/2021/5530650 45. Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, Nachman JB, Carroll AJ, Heerema NA, Gastier-Foster JM, et al. Prognostic significance of minimal residual disease in high risk B-ALL: A report from Children’s Oncology Group study AALL0232. Blood (2015) 126:964–971. doi: 10.1182/blood-2015- 03-633685 46. Laks D, Longhi F, Wagner MB, Garcia PCR. Avaliação da sobrevida de crianças com leucemia linfocítica aguda tratadas com o protocolo Berlim-Frankfurt- Munique. J Pediatr (Rio J) (2003) 79:149–158. doi: 10.1590/s0021- 75572003000200010 47. Volejnikova J, Mejstrikova E, Valova T, Reznickova L, Hodonska L, Mihal V, Sterba J, Jabali Y, Prochazkova D, Blazek B, et al. Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis. Haematologica (2011) 96:1815–1821. doi: 10.3324/haematol.2011.042937 48. Pui CH, Carroll WL, Meshinchi S, Arceci RJ. Biology, risk stratification, and therapy of pediatric acute leukemias: An update. Journal of Clinical Oncology (2011) 29:551–565. doi: 10.1200/JCO.2010.30.7405 49. Ratei R, Basso G, Dworzak M, Gaipa G, Veltroni M, Rhein P, Biondi A, Schrappe M, Ludwig WD, Karawajew L. Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction. Leukemia 2009 23:3 (2008) 23:528–534. doi: 10.1038/leu.2008.324 50. Colby-Graham MF, Chordas C. The childhood leukemias. J Pediatr Nurs (2003) 18:87–95. doi: 10.1053/jpdn.2003.9 51. Biondi A, Conter V, Chandy M, Ewald P, Lucia de Martino Lee M, Radhakrishnan VS, Rotchanapanya W, Scanlan P, Patrick Smith O, Togo B, et al. Precursor B- 65 cell acute lymphoblastic leukaemia—a global view. Br J Haematol (2022) 196:530–547. doi: 10.1111/bjh.17959 52. Pui CH, Mullighan CG, Evans WE, Relling M V. Pediatric acute lymphoblastic leukemia: Where are we going and how do we get there? Blood (2012) 120:1165– 1174. doi: 10.1182/blood-2012-05-378943 53. Campana D. Minimal residual disease in acute lymphoblastic leukemia. Hematology / the Education Program of the American Society of Hematology American Society of Hematology Education Program (2010) 2010:7–12. doi: 10.1182/asheducation-2010.1.7 54. Antônio ROJPBB. Mielograma e Imunofenotipagem por citometria de fluxo em hematologia. Roco (2019) 55. Cherian S, Soma LA. How i diagnose minimal/measurable residual disease in b lymphoblastic leukemia/lymphoma by flow cytometry. Am J Clin Pathol (2021) 155:38–54. doi: 10.1093/ajcp/aqaa242 56. Maciorowski Z, Chattopadhyay PK, Jain P. Basic multicolor flow cytometry. Curr Protoc Immunol (2017) 2017:5.4.1-5.4.38. doi: 10.1002/cpim.26 57. Villas BH. Flow cytometry: an overview. Cell Vis (2018) 5:56–61. doi: 10.1007/978-94-017-0623-0_1 58. Dai Q, Liu X, Yang H, Guo S, Wang Y, Peng L, Ye L, Chen L, Lai C, Chen Q, et al. No prognostic significance of immunophenotypic changes at the end of remission induction therapy in children with B-lineage acute lymphoblastic leukemia. Leuk Res (2018) 68:57–61. doi: 10.1016/j.leukres.2018.03.001 59. Ikoma-Colturato MRV, Beltrame MP, Furtado FM, Pimenta G, da Costa ES, Azambuja AP, Malvezzi M, Yamamoto M. Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation. Hematol Transfus Cell Ther (2021) 43:332–340. doi: 10.1016/j.htct.2020.09.148 60. Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, Sobral da Costa E, Kotrová M, Novakova M, Sonneveld E, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood (2017) 129:347–357. doi: 10.1182/blood-2016-07- 726307 61. Dekker JD, Rhee C, Hu Z, Lee B-K, Lee J, Iyer VR, Ehrlich LIR, Georgiou G, 2^ HOT, Ippolito GC, et al. Lymphoid origin of a lineage of intrinsically activated plasmacytoid dendritic cell in mice and humans. bioRxiv (2018)310680. 62. Almeida PSR, Saddi VA. Monitoramento de doença residual mínima em leucemia mielóide crônica por PCR em tempo real. Rev Bras Hematol Hemoter (2007) 29:382–386. doi: 10.1590/S1516-84842007000400012 63. Correia RP, Bento LC, de Sousa FA, Barroso R de S, Campregher P V., Bacal NS. How I investigate minimal residual disease in acute lymphoblastic leukemia. Int J Lab Hematol (2021) 43:354–363. doi: 10.1111/ijlh.13463 66 64. Theunissen P, Mejstrikova E, Sedek L, Van Der Sluijs-Gelling AJ, Gaipa G, Bartels M, Sobral da Costa E, Kotrová M, Novakova M, Sonneveld E, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood (2017) 129:347–357. doi: 10.1182/blood- 2016-07-726307 65. Gaipa G, Buracchi C, Biondi A. Flow cytometry for minimal residual disease testing in acute leukemia: opportunities and challenges. Expert Rev Mol Diagn (2018) 18:775–787. doi: 10.1080/14737159.2018.1504680 66. Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, Ferrara F, Peta A, Ciolli S, Deplano W, et al. Treatment of adult acute lymphoblastic leukemia (ALL): Long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood (2002) 99:863–871. doi: 10.1182/blood.V99.3.863 67. Christiane Pott, Monika Brüggemann, Matthias Ritgen, Vincent HJ van der Velden, Jacques JM van Dongen MK. Detection in B-Cell Non-Hodgkin Lymphomas Using Ig Gene Rearrangements and Crhromosomal Translocations as Targets for Real-Time qPCR. Methods in Molecular Biology (2019) doi: 10.1007/978-1-4939-9151-8_9 68. Wright G, Watt E, Inglott S, Brooks T, Bartram J, Adams SP. Clinical benefit of a high-throughput sequencing approach for minimal residual disease in acute lymphoblastic leukemia. Pediatr Blood Cancer (2019) 66:1–7. doi: 10.1002/pbc.27787 69. Kim IS. Minimal residual disease in acute lymphoblastic leukemia: Technical aspects and implications for clinical interpretation. Blood Res (2020) 55:19–26. doi: 10.5045/br.2020.S004 70. Pui C. Acute lymphoblastic leukemia in children. (2000)3–12. 71. Paganin M, Fabbri G, Conter V, Barisone E, Polato K, Cazzaniga G, Giraldi E, Fagioli F, Aricò M, Valsecchi MG, et al. Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia. Journal of Clinical Oncology (2014) 32:3553–3558. doi: 10.1200/JCO.2014.56.0698 72. Van Dongen JJM, Van Der Velden VHJ, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies. Blood (2015) 125:3996–4009. doi: z 73. Chen X, Wood BL. How do we measure MRD in ALL and how should measurements affect decisions. Re: Treatment and prognosis? Best Pract Res Clin Haematol (2017) 30:237–248. doi: 10.1016/j.beha.2017.07.002 74. Luskin MR, Murakami MA, Manalis SR, Weinstock DM. Targeting minimal residual disease: A path to cure? Nat Rev Cancer (2018) 18:255–263. doi: 10.1038/nrc.2017.125 75. Saygin C, Cannova J, Stock W, Muffly L. Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. Haematologica (2022) 107:2783–2793. doi: 10.3324/haematol.2022.280638 67 76. Cazé MO, Bueno D, Santos MEF Dos. Estudo referencial de um protocolo quimioterápico para leucemia linfocítica aguda infantil. Rev HCPA & Fac Med Univ Fed Rio Gd do Sul (2010) 30:5–12. 77. Künz T, Hauswirth AW, Hetzenauer G, Rudzki J, Nachbaur D, Steiner N. Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL). Cancers (Basel) (2022) 14: doi: 10.3390/cancers14174290 78. Cheng SH, Lau KM, Li CK, Chan NPH, Ip RKL, Cheng CK, Lee V, Shing MMK, Leung AWK, Ha SY, et al. Minimal Residual Disease-Based Risk Stratification in Chinese Childhood Acute Lymphoblastic Leukemia by Flow Cytometry and Plasma DNA Quantitative Polymerase Chain Reaction. PLoS One (2013) 8: doi: 10.1371/journal.pone.0069467 79. Quiroz E, Aldoss I, Pullarkat V, Rego E, Marcucci G, Douer D. The emerging story of acute lymphoblastic leukemia among the Latin American population – biological and clinical implications. Blood Rev (2019) 33:98–105. doi: 10.1016/j.blre.2018.08.002 80. Ikoma-Colturato MRV, Beltrame MP, Furtado FM, Pimenta G, da Costa ES, Azambuja AP, Malvezzi M, Yamamoto M. Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation. Hematol Transfus Cell Ther (2021) 43:332–340. doi: 10.1016/j.htct.2020.09.148 81. Lúcio P, Parreira A, van den Beemd M, van Lochem E, van Wering E, Baars E, Porwit-MacDonald A, Bjorklund E, Gaipa G, Biondi A, et al. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. (1999). 419–427 p. http://www.stockton-press.co.uk/leu 82. Depince-Berger AE, Aanei C, Iobagiu C, Jeraiby M, Lambert C. New tools in cytometry. Morphologie (2016) 100:199–209. doi: 10.1016/j.morpho.2016.05.001 83. Fuda F, Chen W. Minimal/Measurable Residual Disease Detection in Acute Leukemias by Multiparameter Flow Cytometry. Curr Hematol Malig Rep (2018) 13:455–466. doi: 10.1007/s11899-018-0479-1 84. Weng XQ, Shen Y, Sheng Y, Chen B, Wang JH, Li JM, Mi JQ, Chen QS, Zhu YM, Jiang CL, et al. Prognostic significance of monitoring leukemia-associated immunophenotypes by eight-color flow cytometry in adult B-acute lymphoblastic leukemia. Blood Cancer J (2013) 3: doi: 10.1038/bcj.2013.31 85. Coustan-Smith E, Campana D. Immunologic minimal residual disease detection in acute lymphoblastic leukemia: A comparative approach to molecular testing. Best Pract Res Clin Haematol (2010) 23:347–358. doi: 10.1016/j.beha.2010.07.007 86. Luria D, Rosenthal E, Steinberg D, Kodman Y, Safanaiev M, Amariglio N, Avigad S, Stark B, Izraeli S. Prospective comparison of two flow cytometry methodologies for monitoring minimal residual disease in a multicenter treatment protocol of childhood acute lymphoblastic leukemia. Cytometry B Clin Cytom (2010) 78:365– 371. doi: 10.1002/cyto.b.20532 68 87. Chen W, Luu HS. Immunophenotyping by multiparameter flow cytometry. Methods in Molecular Biology (2017) 1633:51–73. doi: 10.1007/978-1-4939- 7142-8_4 88. Felice MS, Zubizarreta PA, Alfaro EM, Sackmann-Muriel F. Childhood Acute Lymphoblastic Leukemia: Prognostic Value of Initial Peripheral Blast Count in Good Responders to Prednisone. (2001). 89. Lauten M, Möricke A, Beier R, Zimmermann M, Stanulla M, Meissner B, Odenwald E, Attarbaschi A, Niemeyer C, Niggli F, et al. Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: Differential effects in precursor B-cell and T-cell leukemia. Haematologica (2012) 97:1048–1056. doi: 10.3324/haematol.2011.047613
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United Statesen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.subjectLeucemia pediatrica
dc.subjectCélula leucêmica residual
dc.subjectDoença residual mensurável
dc.subjectCitometria de fluxo
dc.subjectPrognóstico
dc.titleImpacto da detecção de blastos leucêmicos durante o protocolo de tratamento dos pacientes pediátricos com leucemia linfoblástica aguda de células b: implicações clínicas elaboratoriais
dc.title.alternativeImpact of leukemic blast detection during the treatment protocol for pediatric patients with B-cell acute lymphoblastic leukemia: clinical and laboratorial implications
dc.typeDissertação

Arquivos

Pacote original

Agora exibindo 1 - 1 de 1
Carregando...
Imagem de Miniatura
Nome:
Impactos_da_detecção_de_blastos.pdf
Tamanho:
2.11 MB
Formato:
Adobe Portable Document Format