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Annals of Hematology

, Volume 94, Issue 8, pp 1347–1356 | Cite as

All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia: a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies

  • Miguel A. SanzEmail author
  • Pau Montesinos
  • Haesook T. Kim
  • Guillermo J. Ruiz-Argüelles
  • María S. Undurraga
  • María R. Uriarte
  • Lem Martínez
  • Rafael H. Jacomo
  • Homero Gutiérrez-Aguirre
  • Raul A. M. Melo
  • Rosane Bittencourt
  • Ricardo Pasquini
  • Katia Pagnano
  • Evandro M. Fagundes
  • Edo Vellenga
  • Alexandra Holowiecka
  • Ana J. González-Huerta
  • Pascual Fernández
  • Javier De la Serna
  • Salut Brunet
  • Elena De Lisa
  • José González-Campos
  • José M. Ribera
  • Isabel Krsnik
  • Arnold Ganser
  • Nancy Berliner
  • Raul C. Ribeiro
  • Francesco Lo-Coco
  • Bob Löwenberg
  • Eduardo M. Rego
  • on behalf of the IC-APL and PETHEMA and HOVON Groups
Original Article

Abstract

Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diagnosed APL were compared using matched-pair analysis. One was conducted by the PETHEMA/HOVON group with idarubicin and the other by the International Consortium on APL (IC-APL) using daunorubicin. Three hundred and fifty patients from the PETHEMA/HOVON cohort were matched with 175 patients in the IC-APL cohort, adjusting for the significantly unbalanced presenting features of the two entire cohorts. Complete remission (CR) rate was significantly higher in the PETHEMA/HOVON (94 %) than in the IC-APL cohort (85 %) (P = 0.002). The distribution of causes of induction failure and the time to achieve CR were similar in both cohorts. Patients who achieved CR had comparable cumulative incidence of relapse and disease-free survival rates, but lower overall and event-free survivals were observed in the IC-APL cohort, which was mainly due to a higher death rate during induction therapy. A higher death rate during consolidation therapy was also observed in the IC-APL. These results show that daunorubicin and idarubicin have similar antileukaemic efficacy in terms of primary resistance, molecular persistence, as well as molecular and haematological relapse rates when combined with ATRA in treatment of APL. However, a higher toxic death rate during induction and consolidation therapy was observed in the IC-APL cohort. This trial was registered at www.clinicaltrials.gov as #NCT00408278 [ClinicalTrials.gov].

Keywords

Acute promyelocytic leukaemia Risk-adapted therapy All-trans retinoic acid Anthracyclines Cytarabine Prognostic factors Matched-pair analysis 

Notes

Acknowledgments

The authors thank all participating institutions and clinicians in the PETHEMA/HOVON and IC-APL studies. This work was supported in part by Cooperative Research Thematic Network Grant RD12/0036/014 (Instituto de Salud Carlos III and European Regional Development Fund). The authors are thankful for the support of the American Society of Hematology, Fondazione Umberto Veronesi, Roche South Arabia, Fundação de Apoio à Pesquisa do Estado de São Paulo (Grant No. 1998/14247-6), Fundacion Mexicana para la Salud, St. Jude Children’s Research Hospital and Cephalon Europe.

Authors’ contribution

M.A.S. conceived the study and analysed and interpreted the data; M.A.S., F.L-C., A.G., N.B., R.C.R., B.L. and E.M.R. wrote the paper; P.M. and H. K. performed the statistical analyses; E.M.R., G.J.R.-A., M.S.U. and L.M. were the national coordinators in Brazil, Mexico, Chile and Uruguay, respectively; M.R.U., R.H.J., H. G-A., R.A.M.M., R.B., R.P., K.P., E.M.F., E.V., A.H., Ch.R., P.F., J.d.S., S.B., E.d.L, J.G-C., J.M.R. and I.K. included data of patients treated in their institutions, reviewed the manuscript and contributed to the final draft.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Miguel A. Sanz
    • 1
    • 2
    Email author
  • Pau Montesinos
    • 1
    • 2
  • Haesook T. Kim
    • 3
  • Guillermo J. Ruiz-Argüelles
    • 4
  • María S. Undurraga
    • 5
  • María R. Uriarte
    • 6
  • Lem Martínez
    • 6
  • Rafael H. Jacomo
    • 7
  • Homero Gutiérrez-Aguirre
    • 8
  • Raul A. M. Melo
    • 9
  • Rosane Bittencourt
    • 10
  • Ricardo Pasquini
    • 11
  • Katia Pagnano
    • 12
  • Evandro M. Fagundes
    • 13
  • Edo Vellenga
    • 14
  • Alexandra Holowiecka
    • 15
  • Ana J. González-Huerta
    • 16
  • Pascual Fernández
    • 17
  • Javier De la Serna
    • 18
  • Salut Brunet
    • 19
  • Elena De Lisa
    • 20
  • José González-Campos
    • 21
  • José M. Ribera
    • 22
  • Isabel Krsnik
    • 23
  • Arnold Ganser
    • 24
  • Nancy Berliner
    • 25
  • Raul C. Ribeiro
    • 26
  • Francesco Lo-Coco
    • 27
    • 28
  • Bob Löwenberg
    • 29
  • Eduardo M. Rego
    • 7
  • on behalf of the IC-APL and PETHEMA and HOVON Groups
  1. 1.Hematology DepartmentUniversity Hospital La FeValenciaSpain
  2. 2.Department of MedicineUniversity of ValenciaValenciaSpain
  3. 3.Department of Biostatistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Clinica Ruiz de PueblaPueblaMexico
  5. 5.Department of HematologyHospital del SalvadorSantiagoChile
  6. 6.Asociación Española Primera de Socorros MutuosMontevideoUruguay
  7. 7.Hematology/Oncology Division, Department of Internal Medicine, Medical School of Ribeirão Preto and Center for Cell Based TherapyUniversity of São PauloRibeirão PretoBrazil
  8. 8.Hematology DivisionHospital Universitario Dr José E. GonzálezMonterreyMexico
  9. 9.Fundação HEMOPERecifeBrazil
  10. 10.Hematology DivisionFederal University of Rio Grande do SulPorto AlegreBrazil
  11. 11.Hematology DivisionFederal University of ParanáCuritibaBrazil
  12. 12.Hematology and Hemotherapy CenterUniversity of Campinas UNICAMPCampinasBrazil
  13. 13.Hematology DivisionFederal University of Minas GeraisBelo HorizonteBrazil
  14. 14.Department of HematologyUniversity Medical Center GroningenGroningenThe Netherlands
  15. 15.Department of HematologySilesian Medical UniversityKatowicePoland
  16. 16.Hospital Central de AsturiasOviedoSpain
  17. 17.Department of HematologyHospital General Universitario de AlicanteAlicanteSpain
  18. 18.Department of HematologyHospital 12 de OctubreMadridSpain
  19. 19.Hospital Sant PauBarcelonaSpain
  20. 20.Department of HematologyHospital MacielMontevideoUruguay
  21. 21.Department of HematologyHospital Virgen del RocioSevillaSpain
  22. 22.Department of HematologyHospital Germans Trias i PujolBadalonaSpain
  23. 23.Department of HematologyHospital Puerta de HierroMadridSpain
  24. 24.Department of Hematology, Hemostasis, Oncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  25. 25.Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  26. 26.Department of OncologySt. Jude Children’s Research HospitalMemphisUSA
  27. 27.Department of BiopathologyUniversity Tor VergataRomeItaly
  28. 28.Santa Lucia FoundationRomeItaly
  29. 29.Department of HematologyErasmus University Medical CenterRotterdamNetherlands

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