Skip to main content
Erschienen in: International Journal of Hematology 3/2014

01.03.2014 | Original Article

Prognostic significance of flow cytometric residual disease, dysregulated neutrophils/monocytes, and hematogones in adult acute myeloid leukemia in first remission

verfasst von: Sung-Chao Chu, Tso-Fu Wang, Yu-Chieh Su, Ruey-Ho Kao, Yi-Feng Wu, Dian-Kun Li, Szu-Chin Li, Chi-Cheng Li, Denise A. Wells, Michael R. Loken

Erschienen in: International Journal of Hematology | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Fifty-one consecutive non-M3 acute myeloid leukemia (AML) patients who had achieved morphologic complete remission (mCR) after induction chemotherapy were enrolled in the present study. Three characteristics of bone marrow (BM) composition analyzed by flow cytometry were combined to determine the prognostic impact. A standardized panel of reagents was used to detect residual disease of aberrant myeloid progenitor cells (RD), identify neutrophils/monocytes with dysregulated immunophenotype (dysregulated neutro/mono) and quantify the appearance of CD34+ B-progenitor-related cluster (hematogones) simultaneously in post-induction BM of adult AML patients. Patients who had detectable RD ≥0.2 % exhibited significantly lower median leukemia-free survival (LFS) than those who did not (13.5 vs. 48.0 months; P = 0.042). Dysregulated neutro/mono abnormalities assessed by this flow cytometric scoring system (FCSS ≥2) predicted shorter LFS (8.0 vs. 39.0 months; P = 0.008). While B-progenitor-related cluster size ≥5 % predicted improved outcome, with longer LFS (not reached vs. 13.5 months; P = 0.023) and better overall survival (not reached vs. 24.0 months; P = 0.027). The proposed RD/dysregulated neutro/mono/hematogones score showed a new risk groups with different LFS in the overall patients (P = 0.0006) as well as in the subgroup of intermediate cytogenetic risk (P = 0.001). The RD/dysregulated neutro/mono/hematogones score assessed by flow cytometry for adult AML in mCR may offer a rapid and practical risk assessment providing better refinement in risk-adapted management after induction chemotherapy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.PubMedCrossRef Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.PubMedCrossRef
2.
Zurück zum Zitat Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematol Am Soc Hematol Educ Progr 2009;385–95. Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematol Am Soc Hematol Educ Progr 2009;385–95.
3.
Zurück zum Zitat Walter RB, Gooley TA, Wood BL, et al. Impact of pretransplantation minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol. 2011;29:1190–7.PubMedCentralPubMedCrossRef Walter RB, Gooley TA, Wood BL, et al. Impact of pretransplantation minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol. 2011;29:1190–7.PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat San Miguel JF, Martinez A, Macedo A, et al. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood. 1997;90:2465–70.PubMed San Miguel JF, Martinez A, Macedo A, et al. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood. 1997;90:2465–70.PubMed
5.
Zurück zum Zitat Kern W, Voskova D, Schoch C, Hiddemann W, Schnittger S, Haferlach T. Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia. Blood. 2004;104:3078–85.PubMedCrossRef Kern W, Voskova D, Schoch C, Hiddemann W, Schnittger S, Haferlach T. Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia. Blood. 2004;104:3078–85.PubMedCrossRef
6.
Zurück zum Zitat Westers TM, Ireland R, Kern W, et al. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. Leukemia. 2012;26:1730–41.PubMedCrossRef Westers TM, Ireland R, Kern W, et al. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. Leukemia. 2012;26:1730–41.PubMedCrossRef
7.
Zurück zum Zitat Chantepie SP, Salaun V, Parienti JJ, et al. Hematogones: a new prognostic factor for acute myeloblastic leukemia. Blood. 2011;117:1315–8.PubMedCrossRef Chantepie SP, Salaun V, Parienti JJ, et al. Hematogones: a new prognostic factor for acute myeloblastic leukemia. Blood. 2011;117:1315–8.PubMedCrossRef
8.
Zurück zum Zitat Honebrink T, Dayton V, Burke MJ, et al. Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia. Biol Blood Marrow Transpl. 2012;18:930–6.CrossRef Honebrink T, Dayton V, Burke MJ, et al. Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia. Biol Blood Marrow Transpl. 2012;18:930–6.CrossRef
9.
Zurück zum Zitat Reichle A, Rothe G, Krause S, et al. Transplant characteristics: minimal residual disease and impaired megakaryocytic colony growth as sensitive parameters for predicting relapse in acute myeloid leukemia. Leukemia. 1999;13:1227–34.PubMedCrossRef Reichle A, Rothe G, Krause S, et al. Transplant characteristics: minimal residual disease and impaired megakaryocytic colony growth as sensitive parameters for predicting relapse in acute myeloid leukemia. Leukemia. 1999;13:1227–34.PubMedCrossRef
10.
Zurück zum Zitat Wells DA, Benesch M, Loken MR, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102:394–403.PubMedCrossRef Wells DA, Benesch M, Loken MR, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102:394–403.PubMedCrossRef
11.
Zurück zum Zitat Chu SC, Wang TF, Li CC, et al. Flow cytometric scoring system as a diagnostic and prognostic tool in myelodysplastic syndromes. Leuk Res. 2011;35:868–73.PubMedCrossRef Chu SC, Wang TF, Li CC, et al. Flow cytometric scoring system as a diagnostic and prognostic tool in myelodysplastic syndromes. Leuk Res. 2011;35:868–73.PubMedCrossRef
12.
Zurück zum Zitat van de Loosdrecht AA, Westers TM, Westra AH, Drager AM, van der Velden VH, Ossenkoppele GJ. Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood. 2008;111:1067–77.PubMedCrossRef van de Loosdrecht AA, Westers TM, Westra AH, Drager AM, van der Velden VH, Ossenkoppele GJ. Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood. 2008;111:1067–77.PubMedCrossRef
13.
Zurück zum Zitat Scott BL, Wells DA, Loken MR, Myerson D, Leisenring WM, Deeg HJ. Validation of a flow cytometric scoring system as a prognostic indicator for posttransplantation outcome in patients with myelodysplastic syndrome. Blood. 2008;112:2681–6.PubMedCentralPubMedCrossRef Scott BL, Wells DA, Loken MR, Myerson D, Leisenring WM, Deeg HJ. Validation of a flow cytometric scoring system as a prognostic indicator for posttransplantation outcome in patients with myelodysplastic syndrome. Blood. 2008;112:2681–6.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Kimby E, Nygren P, Glimelius B. A systematic overview of chemotherapy effects in acute myeloid leukaemia. Acta Oncol. 2001;40:231–52.PubMedCrossRef Kimby E, Nygren P, Glimelius B. A systematic overview of chemotherapy effects in acute myeloid leukaemia. Acta Oncol. 2001;40:231–52.PubMedCrossRef
15.
Zurück zum Zitat Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.PubMedCrossRef Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.PubMedCrossRef
16.
Zurück zum Zitat Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–20.PubMedCrossRef Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–20.PubMedCrossRef
17.
Zurück zum Zitat Stelzer GT, Shults KE, Loken MR. CD45 gating for routine flow cytometric analysis of human bone marrow specimens. Ann N Y Acad Sci. 1993;677:265–80.PubMedCrossRef Stelzer GT, Shults KE, Loken MR. CD45 gating for routine flow cytometric analysis of human bone marrow specimens. Ann N Y Acad Sci. 1993;677:265–80.PubMedCrossRef
18.
Zurück zum Zitat Ogata K, Kishikawa Y, Satoh C, Tamura H, Dan K, Hayashi A. Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes. Blood. 2006;108:1037–44.PubMedCrossRef Ogata K, Kishikawa Y, Satoh C, Tamura H, Dan K, Hayashi A. Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes. Blood. 2006;108:1037–44.PubMedCrossRef
19.
Zurück zum Zitat Della Porta MG, Picone C, Pascutto C, et al. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study. Haematologica. 2012;97:1209–17.PubMedCentralPubMedCrossRef Della Porta MG, Picone C, Pascutto C, et al. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study. Haematologica. 2012;97:1209–17.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Campana D. Progress of minimal residual disease studies in childhood acute leukemia. Curr Hematol Malig Rep. 2010;5:169–76.PubMedCrossRef Campana D. Progress of minimal residual disease studies in childhood acute leukemia. Curr Hematol Malig Rep. 2010;5:169–76.PubMedCrossRef
21.
Zurück zum Zitat Loken MR, Alonzo TA, Pardo L, et al. Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children’s Oncology Group. Blood. 2012;120:1581–8.PubMedCentralPubMedCrossRef Loken MR, Alonzo TA, Pardo L, et al. Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children’s Oncology Group. Blood. 2012;120:1581–8.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Babusikova O, Zeleznikova T, Kirschnerova G, Kankuri E. Hematogones in acute leukemia during and after therapy. Leuk Lymph. 2008;49:1935–44.CrossRef Babusikova O, Zeleznikova T, Kirschnerova G, Kankuri E. Hematogones in acute leukemia during and after therapy. Leuk Lymph. 2008;49:1935–44.CrossRef
23.
Zurück zum Zitat Satoh C, Dan K, Yamashita T, Jo R, Tamura H, Ogata K. Flow cytometric parameters with little interexaminer variability for diagnosing low-grade myelodysplastic syndromes. Leuk Res. 2008;32:699–707.PubMedCrossRef Satoh C, Dan K, Yamashita T, Jo R, Tamura H, Ogata K. Flow cytometric parameters with little interexaminer variability for diagnosing low-grade myelodysplastic syndromes. Leuk Res. 2008;32:699–707.PubMedCrossRef
24.
Zurück zum Zitat Chow KF, Sevilla DW, Colovai AI, Bhagat G, Alobeid B. Hematogones are markedly decreased in chronic myeloid leukemia: multiparametric flow cytometric analysis. Leuk Lymphoma. 2011;52:680–6.PubMedCrossRef Chow KF, Sevilla DW, Colovai AI, Bhagat G, Alobeid B. Hematogones are markedly decreased in chronic myeloid leukemia: multiparametric flow cytometric analysis. Leuk Lymphoma. 2011;52:680–6.PubMedCrossRef
25.
Zurück zum Zitat McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood. 2001;98:2498–507.PubMedCrossRef McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood. 2001;98:2498–507.PubMedCrossRef
26.
Zurück zum Zitat van de Loosdrecht AA, Alhan C, Bene MC, et al. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes. Haematologica. 2009;94:1124–34.PubMedCentralPubMedCrossRef van de Loosdrecht AA, Alhan C, Bene MC, et al. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes. Haematologica. 2009;94:1124–34.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Maftoun-Banankhah S, Maleki A, Karandikar NJ, et al. Multiparameter flow cytometric analysis reveals low percentage of bone marrow hematogones in myelodysplastic syndromes. Am J Clin Pathol. 2008;129:300–8.PubMedCrossRef Maftoun-Banankhah S, Maleki A, Karandikar NJ, et al. Multiparameter flow cytometric analysis reveals low percentage of bone marrow hematogones in myelodysplastic syndromes. Am J Clin Pathol. 2008;129:300–8.PubMedCrossRef
29.
Zurück zum Zitat Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366:1079–89.PubMedCentralPubMedCrossRef Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366:1079–89.PubMedCentralPubMedCrossRef
Metadaten
Titel
Prognostic significance of flow cytometric residual disease, dysregulated neutrophils/monocytes, and hematogones in adult acute myeloid leukemia in first remission
verfasst von
Sung-Chao Chu
Tso-Fu Wang
Yu-Chieh Su
Ruey-Ho Kao
Yi-Feng Wu
Dian-Kun Li
Szu-Chin Li
Chi-Cheng Li
Denise A. Wells
Michael R. Loken
Publikationsdatum
01.03.2014
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 3/2014
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-014-1525-y

Weitere Artikel der Ausgabe 3/2014

International Journal of Hematology 3/2014 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.