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Immunophenotypic alterations of bone marrow myeloid cell compartments in multiple myeloma patients predict for myelodysplasia-associated cytogenetic alterations

Leukemia volume 28, pages 1747–1750 (2014)Cite this article

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Treatment for multiple myeloma (MM) has seen major improvements in the past 15 years.1 However, specific treatment strategies (e.g. alkylators or maintenance therapy with lenalidomide alone or in combination with melphalan) have been associated with an increased risk of developing secondary primary malignancies,2, 3, 4, 5 whose underlying mechanisms remain poorly understood.6 Of note, a greater risk for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) was also reported in patients with IgG/IgA monoclonal gammopathy of undetermined significance (MGUS), thus showing no treatment influence.7 Importantly, the latter observation has been recently confirmed in a large population study from the Olmsted County (MN, USA), in which an increased risk for MDS was noted among MGUS patients.8 Although the survival benefit of alkylators or lenalidomide outweighs the potential risk of secondary primary malignancies, it would be of great value to identify patients at high risk of developing secondary primary malignancies. Moreover, it has been recently reported that the presence of cytogenetic alterations associated with MDS precedes the diagnosis of clinical MDS/AML.9

Multiparameter flow cytometry immunophenotyping is currently considered a sensitive co-adjuvant test in the diagnostic screening for MDS through the identification of MDS-associated phenotypic alterations (MDS-PAs) at the protein expression level in different bone marrow (BM) hematopoietic cell compartments.10 Of note, the presence of MDS-PAs has been recently described in a significant proportion (>80%) of adult patients with the novo AML in association with clonal residual hematopoiesis.11 Similarly, some MM patients also show MDS-PA at diagnosis.12

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References

  1. Usmani SZ, Crowley J, Hoering A, Mitchell A, Waheed S, Nair B et al. Improvement in long-term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured? Leukemia 2013; 27: 226–232.

    Article  CAS  Google Scholar 

  2. Usmani SZ, Sexton R, Hoering A, Heuck CJ, Nair B, Waheed S et al. Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance. Blood 2012; 120: 1597–1600.

    Article  CAS  Google Scholar 

  3. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. Lenalidomide after stem-cell transplantation for multiple myeloma. New Engl J Med 2012; 366: 1770–1781.

    Article  CAS  Google Scholar 

  4. Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. New Engl J Med 2012; 366: 1759–1769.

    Article  CAS  Google Scholar 

  5. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. New Engl J Medicine 2012; 366: 1782–1791.

    Article  CAS  Google Scholar 

  6. Rajkumar SV . Second to none. Blood, [Comment] 2012; 120: 1537–1539.

    Article  CAS  Google Scholar 

  7. Mailankody S, Pfeiffer RM, Kristinsson SY, Korde N, Bjorkholm M, Goldin LR et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 2011; 118: 4086–4092.

    Article  CAS  Google Scholar 

  8. Roeker LE, Larson DR, Kyle RA, Kumar S, Dispenzieri A, Rajkumar SV . Risk of acute leukemia and myelodysplastic syndromes in patients with monoclonal gammopathy of undetermined significance (MGUS): a population-based study of 17 315 patients. Leukemia 2013; 27: 1391–1393.

    Article  CAS  Google Scholar 

  9. Usmani SZ, Sawyer J, Rosenthal A, Cottler-Fox M, Epstein J, Yaccoby S et al. Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma. Blood 2013; 121: 4753–4757.

    Article  CAS  Google Scholar 

  10. Westers TM, Ireland R, Kern W, Alhan C, Balleisen JS, Bettelheim P et al. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. Leukemia 2012; 26: 1730–1741.

    Article  CAS  Google Scholar 

  11. Fernandez C, Santos-Silva MC, Lopez A, Matarraz S, Jara-Acevedo M, Ciudad J et al. Newly diagnosed adult AML and MPAL patients frequently show clonal residual hematopoiesis. Leukemia 2013; 27: 2149–2156.

    Article  CAS  Google Scholar 

  12. Matarraz S, Paiva B, Diez-Campelo M, Corral LL, Perez E, Mateos MV et al. Myelodysplasia-associated immunophenotypic alterations of bone marrow cells in myeloma: are they present at diagnosis or are they induced by lenalidomide? Haematologica 2012; 97: 1608–1611.

    Article  CAS  Google Scholar 

  13. van Dongen JJ, Lhermitte L, Bottcher S, Almeida J, van der Velden VH, Flores-Montero J et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia 2012; 26: 1908–1975.

    Article  CAS  Google Scholar 

  14. Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009; 23: 2210–2221.

    Article  CAS  Google Scholar 

  15. Kalina T, Flores-Montero J, van der Velden VH, Martin-Ayuso M, Bottcher S, Ritgen M et al. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols. Leukemia 2012; 26: 1986–2010.

    Article  CAS  Google Scholar 

  16. Barlogie B, Tricot G, Haessler J, van Rhee F, Cottler-Fox M, Anaissie E et al. Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989. Blood 2008; 111: 94–100.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Consejería de Sanidad; Gerencia Regional de Salud de Castilla y León (SACYL), Spain (BIO/SA24/13); Fundación Samuel Solórzano Barruso (University of Salamanca, Spain); Black Swan Research Initiative Signature Project of the International Myeloma Foundation, North Hollywood, CA, United States of America; and Cooperative Cancer Research Thematic Network (RTICC): RD12/0036/0048, Instituto de Salud Carlos III-FEDER, Ministerio de Economia y Competitividad, Madrid, Spain.

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Author notes

  1. S Matarraz and B Paiva: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Centro de Investigación del Cáncer (IBMCC, University of Salamanca-CSIC) and IBSAL, Salamanca, Spain

    S Matarraz, S Bárrena, M Jara-Acevedo, M L Gutiérrez, J M Sayagués, M-L Sánchez, P Bárcena & A Orfao

  2. Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain

    B Paiva & J F San Miguel

  3. Department of Hematology, University Hospital, IBSAL and University of Salamanca, Salamanca, Spain

    M Díez-Campelo & M C del Cañizo

  4. Department of Hematology, Hospital Punta Europa, Algeciras, Spain

    M P Garrastazul & M J Berruezo

  5. Department of Hematology, Hospital La Línea, Cádiz, Spain

    J M Duran

  6. Department of Hematology, Hospital Virgen de la Luz, Cuenca, Spain

    C Cerveró

  7. Department of Hematology, Hospital San Jorge, Huesca, Spain

    J A García-Erce

  8. Department of Hematology, Hospital del Mar, Barcelona, Spain

    L Florensa

  9. Department of Hematology, Hospital de Jerez, Cádiz, Spain

    G D Méndez

  10. Department of Hematology, Rio Hortega Hospital, Valladolid, Spain

    O Gutierrez

  11. Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

    J J M van Dongen

Authors
  1. S Matarraz
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  2. B Paiva
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  3. M Díez-Campelo
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  15. L Florensa
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  17. O Gutierrez
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  18. M C del Cañizo
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  19. J J M van Dongen
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  20. J F San Miguel
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  21. A Orfao
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Corresponding author

Correspondence to A Orfao.

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The authors declare no conflict of interest.

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Matarraz, S., Paiva, B., Díez-Campelo, M. et al. Immunophenotypic alterations of bone marrow myeloid cell compartments in multiple myeloma patients predict for myelodysplasia-associated cytogenetic alterations. Leukemia 28, 1747–1750 (2014). https://doi.org/10.1038/leu.2014.103

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