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Annals of Hematology

, Volume 92, Issue 2, pp 249–254 | Cite as

Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia

  • Marta KrejciEmail author
  • Michael Doubek
  • Yvona Brychtova
  • Olga Stehlikova
  • Jana Chovancova
  • Boris Tichy
  • Hana Skuhrova Francova
  • Milan Navratil
  • Miroslav Tomiska
  • Ondrej Horky
  • Sarka Pospisilova
  • Jiri Mayer
Original Article

Abstract

Allogeneic stem cell transplantation (SCT) is a treatment option for patients with poor-risk chronic lymphocytic leukemia (CLL). Sequential use of chemotherapy and reduced-intensity conditioning has been proposed to improve the treatment outcomes. Fludarabine (30 mg/m2/day) and cytarabine (2 g/m2/day) for 4 days (combination of fludarabine with cytarabine; FAraC) were used for cytoreduction. After 3 days of rest, reduced intensity conditioning (RIC) was carried out consisting of 4 Gy total body irradiation, 10–20 mg/kg/day antithymocyte globulin for 3 days, and 40–60 mg/kg/day cyclophosphamide for 2 days. The median time of neutrophil engraftment was 16 days. The most frequent toxicities were grades III/IV infections in 12 of 15 cases and gastrointestinal toxicities in 8 of 15 cases. Remission (complete remission + partial remission) was achieved in 14 of 15 patients (93 %), minimal residual disease negativity according to flowcytometric analysis was observed in 10 patients. Nonrelapse mortality after 1 and 2 years was 7 and 13 %, respectively. After the median follow-up from SCT of 30 months, 80 % of patients were alive (12/15), three patients have died, and three relapses occurred. The FAraC–RIC protocol seems to be a promising approach to the treatment of poor-risk CLL with a high response rate of 93 % and favorable progression-free survival and overall survival of 70 and 85 % at 2 years after SCT, respectively. Other prospective clinical trials are needed to confirm the results of this novel therapeutic strategy.

Keywords

Chronic lymphocytic leukemia Reduced-intensity conditioning Fludarabine Cytarabine 

Notes

Acknowledgments

The work was supported by research grants IGA MZ CR NS10439-3/2009 and MPO FR-TI2/254, research project MSMT MSM0021622430, Project of European Social Fund and the state budget of the Czech Republic SuPReMMe CZ.1.07/2.3.00/20.0045, Central European Institute of Technology CZ.1.05/1.1.00/02.0068. The work was also supported by the European Research Initiative on CLL (ERIC) and the CzEch Leukemia Study Group for Life (CELL).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Marta Krejci
    • 1
    Email author
  • Michael Doubek
    • 1
    • 2
  • Yvona Brychtova
    • 1
  • Olga Stehlikova
    • 1
  • Jana Chovancova
    • 1
  • Boris Tichy
    • 1
    • 2
  • Hana Skuhrova Francova
    • 1
  • Milan Navratil
    • 1
  • Miroslav Tomiska
    • 1
  • Ondrej Horky
    • 1
  • Sarka Pospisilova
    • 1
    • 2
  • Jiri Mayer
    • 1
    • 2
  1. 1.Department of Internal Medicine, Hematology and OncologyUniversity Hospital Brno and Masaryk UniversityBrnoCzech Republic
  2. 2.Central European Institute of TechnologyMasaryk University BrnoBrnoCzech Republic

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