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Efficacy and safety of ruxolitinib and hydroxyurea combination in patients with hyperproliferative myelofibrosis

  • Massimo BrecciaEmail author
  • Luigiana Luciano
  • Novella Pugliese
  • Elena Rossi
  • Mario Tiribelli
  • Emilia Scalzulli
  • Massimiliano Bonifacio
  • Bruno Martino
  • Roberto Latagliata
  • Giulia Benevolo
  • Giovanni Caocci
  • Gianni Binotto
  • Vincenzo Martinelli
  • Michele Cavo
  • Fabrizio Pane
  • Valerio De Stefano
  • Robin Foà
  • Francesca Palandri
Original Article
  • 36 Downloads

Abstract

Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48 weeks, a significant reduction in leucocyte and platelet counts was observed (p = 0.02 and p = 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10 cm below the left costal margin (range, 0–10) to 6 cm (range, 0–15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48 weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.

Keywords

Myelofibrosis Ruxolitinib Hydroxyurea Efficacy 

Notes

Authors’ contribution

MB designed the study, wrote and revised the manuscript; LL, NP, ER, MT, ES, MB, BM, RL, GB, GC, GB, VM, MC, FP, and VDS followed patients; FP and RF critically revised the paper and approved the final version.

Compliance with ethical standards

Conflict of interest

MB received honoraria by Novartis, Pfizer, Incyte, and Celgene. All other authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained for all patients included.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Massimo Breccia
    • 1
    Email author
  • Luigiana Luciano
    • 2
  • Novella Pugliese
    • 2
  • Elena Rossi
    • 3
    • 4
  • Mario Tiribelli
    • 5
  • Emilia Scalzulli
    • 1
  • Massimiliano Bonifacio
    • 6
  • Bruno Martino
    • 7
  • Roberto Latagliata
    • 1
  • Giulia Benevolo
    • 8
  • Giovanni Caocci
    • 9
  • Gianni Binotto
    • 10
  • Vincenzo Martinelli
    • 2
  • Michele Cavo
    • 11
  • Fabrizio Pane
    • 2
  • Valerio De Stefano
    • 3
    • 4
  • Robin Foà
    • 1
  • Francesca Palandri
    • 11
  1. 1.Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto ISapienza UniversityRomeItaly
  2. 2.Federico II UniversityNaplesItaly
  3. 3.Fondazione Policlinico A. Gemelli IRCCSRomeItaly
  4. 4.Institute of HematologyCatholic UniversityRomeItaly
  5. 5.Division of Hematology and BMT, Department of Medical AreaUniversity of UdineUdineItaly
  6. 6.Department of Medicine, Section of HematologyUniversity of VeronaVeronaItaly
  7. 7.Division of HematologyAzienda Ospedaliera ‘Bianchi Melacrino Morelli’Reggio CalabriaItaly
  8. 8.Division of HematologyCittà della Salute e della Scienza HospitalTorinoItaly
  9. 9.Department of Medical Sciences and Public Health, Hematology and Transplant Center, Businco HospitalUniversity of CagliariCagliariItaly
  10. 10.Unit of Hematology and Clinical ImmunologyUniversity of PadovaPadovaItaly
  11. 11.Institute of Hematology “L. and A. Seràgnoli”Sant’Orsola-Malpighi University HospitalBolognaItaly

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