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Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1

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Abstract

Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n = 43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n = 16, 9 %), absent MLD (n = 80, 45 %), or non-evaluable MLD (n = 38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p = 0.03; HR, 95 % CI = 2.3, 1.08–4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p = 0.087, HR, 95 % CI = 1.426, 0.95–2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI = 1.599, 1.026–2.492; p = 0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.

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Funding

This study has been partially supported by grants from the Instituto de Salud Carlos III/FIS P03/0423, PI080158, and PI13/00999; grants RETICS RD06/0020/0004 and RD12/0036/0010, and grant Generalitat de Catalunya SGR 2009 541. MDB holds a Grant from “Fundación Española de Hematología y Hemoterapia” (FEHH).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Hematopathology Unit, Pathology Department, and Hematology Department, IDIBAPS, Hospital Clínic, Barcelona, Spain

    María Rozman, Marina Díaz-Beyá, Marta Pratcorona & Jordi Esteve

  2. Hematology Department, Catalan Institute of Oncology-Germans Trias i Pujol Hospital, Badalona, Universitat Autònoma de Barcelona, Carretera de Canyet s/n, 08320, Badalona, Spain

    José-Tomás Navarro & Fuensanta Millá

  3. Laboratori Citologia Hematològica, Servei de Patologia, Hospital del Mar Medical Research Institute, IMIM, Barcelona, Spain

    Leonor Arenillas & Lourdes Florensa

  4. Hematologic Laboratory Department and Hematology Department, Hospital de Sant Pau, Barcelona, Spain

    Anna Aventín, Josep Nomdedéu, Ana Garrido, Salut Brunet & Jorge Sierra

  5. Hematology Department, Hospital Joan XXIII, Tarragona, Spain

    Teresa Giménez

  6. Pathology Depatment, Hematologic Cytology, Hospital Universitari de Bellvitge, Barcelona, Spain

    Esther Alonso & Esmeralda de la Banda

  7. Laboratory Department, UDIAT, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

    Granada Perea

  8. Hematology Laboratory, Hospital Sant Joan de Déu, Barcelona, Spain

    Mireia Camós

  9. Laboratory of Hematologic Citology, Hematology Department, Hospital Vall d’Hebron, Barcelona, Spain

    Mayda Navarrete

  10. Hematology Department, Hospital Universitari Dr. Josep Trueta, Girona, Spain

    Esperanza Tuset

  11. Josep Carreras Leukemia Research Institute, Barcelona, Spain

    José-Tomás Navarro, Fuensanta Millá, Josep Nomdedéu, Marina Díaz-Beyá, Marta Pratcorona, Salut Brunet, Jorge Sierra & Jordi Esteve

  12. Hospital Clínico Universitario de Valencia, Valencia, Spain

    Blanca Navarro

Authors
  1. María Rozman
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  2. José-Tomás Navarro
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  3. Leonor Arenillas
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  4. Anna Aventín
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  5. Teresa Giménez
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  6. Esther Alonso
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  7. Granada Perea
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  8. Mireia Camós
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  9. Mayda Navarrete
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  11. Lourdes Florensa
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  13. Josep Nomdedéu
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  14. Esmeralda de la Banda
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  15. Marina Díaz-Beyá
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  16. Marta Pratcorona
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  17. Ana Garrido
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  18. Blanca Navarro
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  19. Salut Brunet
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  20. Jorge Sierra
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  21. Jordi Esteve
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Consortia

on behalf of Grup Català de Citologia Hematològica and Spanish CETLAM Group (Grupo Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas Mieloblásticas)

Corresponding author

Correspondence to José-Tomás Navarro.

Additional information

María Rozman and José-Tomás Navarro contributed equally to this manuscript

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Rozman, M., Navarro, JT., Arenillas, L. et al. Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1 . Ann Hematol 93, 1695–1703 (2014). https://doi.org/10.1007/s00277-014-2100-6

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  • DOI: https://doi.org/10.1007/s00277-014-2100-6

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