Annals of Hematology

, Volume 93, Issue 12, pp 2037–2043 | Cite as

Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea

  • Alberto Alvarez-Larrán
  • Luz Martínez-Avilés
  • Juan Carlos Hernández-Boluda
  • Francisca Ferrer-Marín
  • María Luisa Antelo
  • Carmen Burgaleta
  • M. Isabel Mata
  • Blanca Xicoy
  • Alejandra Martínez-Trillos
  • M. Teresa Gómez-Casares
  • M. Antonia Durán
  • Bárbara Marcote
  • Agueda Ancochea
  • Alicia Senín
  • Anna Angona
  • Montse Gómez
  • Vicente Vicente
  • Francisco Cervantes
  • Beatriz Bellosillo
  • Carles Besses
Original Article

Abstract

Therapeutic options for patients with polycythemia vera (PV) and essential thrombocythemia (ET) resistant or intolerant to hydroxyurea are limited. Busulfan is effective as first-line therapy, but there is scarce information on this drug as second-line treatment. The efficacy of busulfan in patients with advanced PV or ET refractory or intolerant to hydroxyurea was assessed in 36 patients (PV n = 15, ET n = 21) treated for a median of 256 days. Complete hematological response (CHR) was achieved in 83 % of patients, after a median time of 203 days (range 92–313). The probability of sustained CHR at 1 and 2 years was 87 and 62 %, respectively. Time to CHR was shorter in patients treated with ≥14 mg of busulfan per week than with lower doses (141 versus 336 days, p = 0.01). Partial molecular response was achieved in three out of nine (33 %) patients. Busulfan was stopped in 27 patients (75 %) due to CHR achievement in 18 cases (67 %), hematological toxicity in 8 cases (30 %), and disease transformation in 1 case. With a median follow-up of 721 days, six patients have died, with the probability of survival at 2 years being 85 %. The probability of thrombosis at 2 years was 11 %. Transformation into acute leukemia or myelodysplastic syndrome was observed in three cases, all of them in a JAK2V617F-negative clone carrying additional mutations. Busulfan, at a dose of 2 mg/day, is an effective option for elderly patients with PV or ET who fail to hydroxyurea, but a significant rate of transformation was observed.

Keywords

Busulfan Polycythemia vera Essential thrombocythemia Hematological response Molecular response 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Alberto Alvarez-Larrán
    • 1
  • Luz Martínez-Avilés
    • 2
  • Juan Carlos Hernández-Boluda
    • 3
  • Francisca Ferrer-Marín
    • 4
  • María Luisa Antelo
    • 5
  • Carmen Burgaleta
    • 6
  • M. Isabel Mata
    • 7
  • Blanca Xicoy
    • 8
  • Alejandra Martínez-Trillos
    • 9
  • M. Teresa Gómez-Casares
    • 10
  • M. Antonia Durán
    • 11
  • Bárbara Marcote
    • 1
  • Agueda Ancochea
    • 1
  • Alicia Senín
    • 1
  • Anna Angona
    • 1
  • Montse Gómez
    • 3
  • Vicente Vicente
    • 4
  • Francisco Cervantes
    • 9
  • Beatriz Bellosillo
    • 2
  • Carles Besses
    • 1
  1. 1.Hematology DepartmentUniversitat Autònoma de Barcelona, Hospital del Mar-IMIMBarcelonaSpain
  2. 2.Pathology Department-IMIMUniversitat Pompeu Fabra, Hospital del MarBarcelonaSpain
  3. 3.Hematology DepartmentHospital ClínicoValenciaSpain
  4. 4.Hematology DepartmentHospital Morales MesseguerMurciaSpain
  5. 5.Hematolology DepartmentComplejo Hospitalario de NavarraPamplonaSpain
  6. 6.Hematology DepartmentHospital Príncipe de AsturiasAlcalá de HenaresSpain
  7. 7.Hematology DepartmentHospital Costa del SolMarbellaSpain
  8. 8.Hematology DepartmentHospital Germans Trias i PujolBadalonaSpain
  9. 9.Hematology DepartmentHospital ClínicBarcelonaSpain
  10. 10.Hematology DepartmentHospital Dr. NegrínLas Palmas de Gran CanariaSpain
  11. 11.Hematology DepartmentHospital Son EspasesPalmaSpain

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