International Journal of Hematology

, Volume 99, Issue 3, pp 296–304 | Cite as

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

  • 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
Original Article
First Online:
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Accepted:

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.

Keywords

Flow cytometry Residual disease Hematogones Acute myeloid leukemia 
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Notes

Acknowledgments

This work was supported by the Buddhist Tzu Chi General Hospital through a Institutional Investigators grant (TCRD99-16). The authors would like to thank all patients, clinicians and technical staff of our institutions for their support of the study. We would also like to specially thank Dr. Raymond Yen-Yu Lo for the fruitful discussion and helpful comment.

Conflict of interest

The authors reported no potential conflicts of interests.

Supplementary material

12185_2014_1525_MOESM1_ESM.doc (332 kb)
Supplementary material 1 (DOC 331 kb)

References

  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematol Am Soc Hematol Educ Progr 2009;385–95.Google Scholar
  3. 3.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    Chantepie SP, Salaun V, Parienti JJ, et al. Hematogones: a new prognostic factor for acute myeloblastic leukemia. Blood. 2011;117:1315–8.PubMedCrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Kimby E, Nygren P, Glimelius B. A systematic overview of chemotherapy effects in acute myeloid leukaemia. Acta Oncol. 2001;40:231–52.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Campana D. Progress of minimal residual disease studies in childhood acute leukemia. Curr Hematol Malig Rep. 2010;5:169–76.PubMedCrossRefGoogle Scholar
  21. 21.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Babusikova O, Zeleznikova T, Kirschnerova G, Kankuri E. Hematogones in acute leukemia during and after therapy. Leuk Lymph. 2008;49:1935–44.CrossRefGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    Walter MJ, Shen D, Ding L, et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med. 2012;366:1090–8.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2014

Authors and Affiliations

  • Sung-Chao Chu
    • 1
    • 2
    • 3
  • Tso-Fu Wang
    • 1
    • 3
  • Yu-Chieh Su
    • 3
    • 4
  • Ruey-Ho Kao
    • 1
    • 3
  • Yi-Feng Wu
    • 1
  • Dian-Kun Li
    • 3
    • 4
  • Szu-Chin Li
    • 4
  • Chi-Cheng Li
    • 5
  • Denise A. Wells
    • 6
  • Michael R. Loken
    • 6
  1. 1.Department of Hematology-OncologyBuddhist Tzu Chi General HospitalHualienTaiwan
  2. 2.Institute of Medical SciencesHualienTaiwan
  3. 3.Department of Medicine, College of MedicineTzu-Chi UniversityHualienTaiwan
  4. 4.Department of Hematology-OncologyBuddhist Tzu Chi General HospitalChiayiTaiwan
  5. 5.Tai Cheng Stem Cell Therapy CenterNational Taiwan University HospitalTaipeiTaiwan
  6. 6.Hematologics Inc.SeattleUSA

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