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

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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.

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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).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Jihlavska 20, 625-00, Brno, Czech Republic

    Marta Krejci, Michael Doubek, Yvona Brychtova, Olga Stehlikova, Jana Chovancova, Boris Tichy, Hana Skuhrova Francova, Milan Navratil, Miroslav Tomiska, Ondrej Horky, Sarka Pospisilova & Jiri Mayer

  2. Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625-00, Brno, Czech Republic

    Michael Doubek, Boris Tichy, Sarka Pospisilova & Jiri Mayer

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  1. Marta Krejci
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  2. Michael Doubek
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  3. Yvona Brychtova
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  11. Sarka Pospisilova
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  12. Jiri Mayer
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Correspondence to Marta Krejci.

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Krejci, M., Doubek, M., Brychtova, Y. et al. Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia. Ann Hematol 92, 249–254 (2013). https://doi.org/10.1007/s00277-012-1579-y

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  • DOI: https://doi.org/10.1007/s00277-012-1579-y

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