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Prognosis in patients with MDS or AML and bone marrow blasts between 10% and 30% is not associated with blast counts but depends on cytogenetic and molecular genetic characteristics

Leukemia volume 25, pages 1361–1364 (2011)Cite this article

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In 2001, the World Health Organization (WHO) classification lowered the threshold for the definition of acute myeloid leukemia (AML) from 30% to 20% of bone marrow (BM) blasts, thus abandoning the category of refractory anemia with excess blasts in transformation (RAEB-T). This modification had been based on similarities in clinical outcomes of RAEB-T and AML patients.1, 2 However, this repeatedly arbitrary threshold of 20% of BM blasts for separation of AML from myelodysplastic syndromes (MDSs) remained in continuous debate.3 To further investigate its justification and potential relevance for diagnosis, prognosis and guidance of treatment decisions, we analyzed clinical outcomes and cytogenetic and molecular genetic features in 276 unselected and consecutive patients with 10–30% of BM blasts, as assessed by BM cytomorphology. The patients were investigated at the MLL Munich Leukemia Laboratory in the period of August 2005 to June 2010. The rationale for study inclusion was the availability of cytomorphology, chromosome-banding analysis/fluorescence in situ hybridization, and parallel PCR mutation analyses results for the markers FLT3-internal tandem duplication (ITD), NPM1 and MLL-PTD (partial tandem duplications). Additional molecular alterations in genes such as RUNX1, NRAS, FLT3-TKD (tyrosine kinase domain), CEBPA or IDH1, were investigated in certain subsets of patients, respectively. The total cohort included 170 males and 106 females (n=276; median age, 68.4 years; range 20.4–88.3 years). According to the 2008 WHO criteria, 96 patients were diagnosed as MDS RAEB-2, as they had 10–19% of myeloblasts, and 180 cases had a diagnosis of AML with 20–30% of myeloblasts (Table 1). Morphological subtypes of AML patients were as follows: M0: n=10; M1: n=2; M2: n=99; M4: n=23; and M6: n=15. Of note, French-American-British (FAB) criteria were not applicable in 31 cases in most cases because of the low cellularity. The WHO category entitled ‘AML with recurrent genetic abnormalities’ was excluded from the study, as the respective subentities are classified by the genetic alterations independent on blast percentages. Treatment of patients was performed according to standard therapy protocols and was adapted to clinical course (information available on 214 cases; MDS: n=73; AML: n=141). As anticipated, MDS patients had a higher rate of supportive care (27/73; 37.0% versus 22/141; 15.6%), and AML patients underwent more frequently intensive chemotherapy regimens (119/141; 84.4% versus 46/73; 63.0%). The number of allogeneic hematopoietic stem cell transplantations was 26 in AML and 11 in MDS. Patients gave written informed consent and the study was approved by the Bavarian Medical Association (Bayerische Landesärztekammer) and followed the Declaration of Helsinki.

Table 1 Clinical characteristics, peripheral blood parameters, FAB subtypes of AML patients, karyotypes and molecular mutations of the 276 patients with MDS or AML and 10–30% of BM blasts investigated in this study
Full size table

All patients were analyzed by BM cytomorphology (May Giemsa Gruenwald staining) and cytochemistry (myeloperoxidase and nonspecific esterase). AML cases were classified according to FAB and WHO (2008) criteria, MDS cases according to the WHO guidelines. Chromosome banding analysis was carried out in all cases according to standard procedures; cytogenetic risk assessment followed the revised Medical Research Council criteria4 in all cases, for patients with AML as with MDS. Molecular analysis was carried out according to previous studies for NPM1, FLT3-ITD, MLL-PTD, FLT3-TKD, NRAS, CEBPA, RUNX1 and IDH1 mutations. Immunophenotyping with multiparameter flow cytometry by five color staining was available in 197 cases. Microarray gene expression profiling data was generated on 26 cases using HG-U133 Plus 2.0 microarrays (Affymetrix, Santa Clara, CA, USA). Sample preparation and data analysis was performed as previously described (see online Supplement).

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References

  1. Estey E, Thall P, Beran M, Kantarjian H, Pierce S, Keating M . Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia [AML]) on outcome of AML-type chemotherapy. Blood 1997; 90: 2969–2977.

    CAS  PubMed  Google Scholar 

  2. Harris NL, Jaffe ES, Diebold J, Flandrin G, Müller-Hermelink HK, Vardiman J et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17: 3835–3849.

    Article  CAS  PubMed  Google Scholar 

  3. Albitar M, Beran M, O'Brien S, Kantarjian H, Frieriech E, Keating M et al. Differences between refractory anemia with excess blasts in transformation and acute myeloid leukemia. Blood 2000; 96: 372–373.

    CAS  PubMed  Google Scholar 

  4. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116: 354–365.

    Article  CAS  Google Scholar 

  5. Itzykson R, Thepot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P et al. Prognostic factors of response and overall survival in 282 higher-risk myelodysplastic syndromes treated with azacitidine. Blood 2011; 117: 403–411.

    Article  CAS  PubMed  Google Scholar 

  6. Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res 2005; 11: 3604–3608.

    Article  CAS  PubMed  Google Scholar 

  7. Santini V, Alessandrino PE, Angelucci E, Barosi G, Billio A, Di MM et al. Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res 2010; 34: 1576–1588.

    Article  CAS  PubMed  Google Scholar 

  8. Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010; 28: 562–569.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department for Stem Cell Transplantation, University of Hamburg, Germany

    U Bacher

  2. MLL Munich Leukemia Laboratory, Munich, Germany

    W Kern, T Alpermann, S Schnittger, A Kohlmann, C Haferlach & T Haferlach

  3. Department of Medical Informatics and Biomathematics, University of Münster, Germany

    H-U Klein & M Dugas

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  1. U Bacher
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Correspondence to T Haferlach.

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Competing interests

WK, CH, SS and TH declare part ownership of the MLL Munich Leukemia Laboratory GmbH. TA and AK are employed by the MLL Munich Leukemia GmbH. The remaining authors declare no conflict of interest.

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Author contributions

UB and TH performed data analysis and wrote the manuscript. TH was responsible for cytomorphology. WK and TA performed data analysis and statistics. WK was responsible for immunophenotyping. Gene expression analysis was performed by AK, HUK und MD. SS was responsible for molecular genetics; CH performed cytogenetics. All authors reviewed the manuscript and approved the final version.

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Bacher, U., Kern, W., Alpermann, T. et al. Prognosis in patients with MDS or AML and bone marrow blasts between 10% and 30% is not associated with blast counts but depends on cytogenetic and molecular genetic characteristics. Leukemia 25, 1361–1364 (2011). https://doi.org/10.1038/leu.2011.80

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