Cytogenetic remission as an important criterion for treatment efficacy in pediatric acute myeloid leukemia

E.W. Fleischman1, O.I. Sokova1, A.V. Popa2, V.S. Nemirovchenko2, L.N. Konstantinova1, and N.F. Metelkova1

1 Institute of Сarcinogenesis, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

2 Pediatric Oncology and Hematology Institute, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation


The results of repeated karyotype analyses in the disease course in 43 children with de novo acute myeloid leukemia (AML) are presented. Patients with clonal bone marrow chromosome abnormalities at diagnosis were included. The follow-up period lasted from 4 to 79 months (median 23 months). The patient cohort was divided into two groups: the standard-risk group and high-risk group. The first group included 13 children with t(8;21)(q22;q22), inv(16)(p13;q22), and t(16;16)(p13;q22). The rest of the patients (30 cases) formed the second group. After assessment of results of bone marrow chromosome analysis at 1–3 months of the treatment, the conclusion was drawn that persistence even single cytogenetically abnormal cell at the start of morphological remission is an unfavorable prognostic sign. It is illustrated by comparison of relapse-free survival (RFS) in two groups of patients: with cytogenetic remission at the onset of morphologic remission (group 1) or with no remission (group 2). RFS was 64.1 ± 10.3 % in the first group. In the second group, one patient is at 20th month of the first CCR and four remaining patients relapsed at 3–20th months (p = 0.018). Another conclusion can be made from our data. Persistence in bone marrow cytogenetically abnormal cells at the beginning of morphological remission can be observed in patients with favorable chromosome markers and patients from other prognostic groups. This finding was prognostically unfavorable regardless of risk-group. Thus, persistence of cytogenetically abnormal cells in bone marrow at the time of morphological remission achieved is a more sensitive criterion for poor outcome than the baseline karyotype (risk groups). The facts obtained show an importance of cytogenetic analysis performance not only at diagnosis but also at the onset of morphologic remission.

Keywords: pediatric acute myeloid leukemia, chromosome markers, cytogenetic remission.

 Read in PDF (RUS)pdficon


  1. Marcucci G., Caligiuri M.A., Bloomfield C.D. Core binding factor (CBF) acute myeloid leukemia: is molecular monitoring useful clinically? Eur. J. Haematol. 2003; 21: 143–54.
  2. Beretta C., Gaipa G., Rossi V. et al. Development of quantitative- PCR method for specific FLT3/ITD monitoring in acute myeloid leukemia. Leukemia 2004; 18: 1441–4.
  3. Grimwade D., Vias P., Freeman S. Assessment of minimal residual disease in acute myeloid leukemia. Curr. Opin. Oncol. 2010; 22: 000–000.
  4. Guieze R., Reneville A., Cauella J.M. et al. Prognostic value of minimal residual disease by real-time quantitative PCR in acute myeloid leukemia with CBFbeta-MYH11 rearrangement: the French experience. Leukemia 2010; 24: 1386–8.
  5. Rizzari C., Cazzaniga G., Goliva T. et al. Predictive factors and survival in childhood acute myeloid leukemia: role of minimal residual disease. Exp. Rev. Anticancer Ther. 2011; 11(9): 1391–401.
  6. Buccisano F., Maurillo L., Del Principe M.I. et al. Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood 2012; 119: 332–41.
  7. Konopleva M., Cheng S.-C., Cortes J.E. et al. Independent prognostic significance of day 21 cytogenetic findings in newly-diagnosed acute myeloid leukemia or refractory anemia with excess blasts. Haematologica 2003; 88: 733–6.
  8. Marcucci G., Mrozek K., Ruppert A.S., Archer A.J. Abnormal cytogenetics at date of morphologic complete remission predicts short overall and disease-free survival, and higher relapse rate in adult acute myeloid leukemia; results from Cancer and Leukemia Group B study 8461. J. Clin. Oncol. 2004; 22: 2410–8.
  9. Balleisen S., Kuendgen A., Hilderbrandt B. et al. Prognoistic relevance of achieving cytogenetic remission in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome following induction chemotherapy. Leuk. Res. 2009; 33: 1189–93.
  10. Chen Y., Cortes J., Estrov Z. et al. Persistence of cytogenetic abnormalities at complete remission after induction in patients with acute myeloid leukemia: prognostic significance and the potential role of allogenic stem cell transplantation. J. Clin. Oncol. 2011; 29: 2507–13.
  11. ISCN-2005: An International System for Human Cytogenetic Nomenclature. Ed. by L.G. Shaffer, N. Tommerup. Basel: Karger, 2005.
  12. ISCN 2009: An International System For Human Cytogenetic Nomenclature. Ed. by L. Schaffer, M. Slovak, L. Campbell. Basel: Karger, 2009.
  13. Grimwade D., Hills R.K., Moorman A.V. et al. Refinement of cytogenetic classification in acute myeloid leukemia: Determination of prognostic significance of rare recurring chromosomal abnormalities amongst 5,876 younger adults treated in the UK Medical Research Council trials. Blood First Edition Paper; prepublished online April 12, 2010. doi: 10.1182/blood-2009-11-254441.
  14. Harrison Ch.J., Hills R.K., Moorman A.V. et al. Cytogenetics of chlidhood acute myeloid leukemia: United Kingdom Medical Research Council treatment trials AML 10 and 12. J. Clin. Oncol. 2010; 28: 2674–81.
  15. von Neuhoff Ch., Reinhardt D., Sander A. et al. Prognostic impact of specific chromosomal aberrations in large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM98. J. Clin. Oncol. 2010; 28: 2682–9.
  16. Schoch C., Kern W., Schnittger S. et al. The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica 2004; 89(9): 1082–90.
  17. Balgobind B.V., Raimondi S.C., Harbott J. et al. Novel prognostic subgroups in childhood 11q23/MLL rearranged acute myeloid leukemia: results of international retrospective study. Blood 2009; 114: 2489–96.
  18. Campana D., Pui C.-H. Detection of minimal residual disease in acute leukemia: Methodological advances and clinical significance. Blood 1995; 85: 1416–24.
  19. Campana D. Determination of minimal residual disease in leukemia patients. Br. J. Haematol. 2003; 121: 823–38.
  20. Muto A., Mori S., Matsushita H. et al. Serial quantification of minimal residual disease for t(8;21) acute myelogenous leukemia with RT-competitive PCR assay. Br. J. Haematol. 1996; 95: 85–94.
  21. Krauter J., Gorlich K., Ottman O. et al. Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias. J. Clin. Oncol. 2003; 21: 4413–22.
  22. Viehman S., Teigler-Schlegel A., Bruch J. et al. Monitoring of minimal residual disease (MRD) by real-time PCR (RQ-RT-PCR) in childhood acute myeloid leukemia with AML1/ETO transcripts rearrangements. Leukemia 2003; 17: 1130–6.
  23. Inaba H., Coustan-Smith E., Cao X. et al. Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. J. Clin. Oncol. 2012; 30: 3625–32.
  24. Флейшман Е.В., Сокова О.И., Попа А.В. и др. Цитогенетический мо- ниторинг острого миелоидного лейкоза детей. Вестн. РАМН 2009; 9: 28–32. [Fleyshman Ye.V., Sokova O.I., Popa A.V. i dr. Tsitogeneticheskiy monitoring ostrogo miyeloidnogo leykoza detey (Cytogenetic monitoring of pediatric acute myeloid leukemia). Vestn. RAMN 2009; 9: 28–32.]
  25. Grimwade D., Walker S., Oliver F. et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. Blood 1998; 92: 2322–33.
  26. Byrd J.C., Mrozek K., Dodge R.K. et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (GALB 8461). Blood 2002; 100: 4325–36.
  27. Pfirrmann M., Ehninger G., Thiede Ch. et al. Prediction of post-remission survival in acute myeloid leukemia: post-hoc analysis in the AML-96 trial. Lancet Oncol. 2012; 13: 207–14.
  28. Takenokuchi M., Yasuda C., Takeuchi K. et al. Quantitative nested reverse transcriptase PCR vs real-time PCR for measuring AML1/ETO (MTG8) transcripts. Clin. Lab. Haem. 2004; 26: 107–14.