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A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome

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Abstract

Recently, a less toxic regimen comprising reduced cyclophosphamide (Cy), fludarabine, and anti-thymocyte globulin (ATG) (Cy-Flu-ATG) was used to condition high-risk patients scheduled for allogeneic hematopoietic cell transplantation (alloHSCT) instead of standard Cy-ATG in patients with severe aplastic anemia (AA). We performed a randomized phase III study to compare the regimen-related toxicities (RRTs) of two different conditioning regimens: Cy-ATG vs. Cy-Flu-ATG. Patients in the Cy-ATG arm received Cy at 200 mg/kg. Those in the Cy-Flu-ATG arm received fludarabine (Flu) at 150 mg/m2 and Cy at 100 mg/kg. A total of 83 patients (40 in the Cy-ATG and 43 in the Cy-Flu-ATG) were enrolled. Seventy-nine patients had AA and four had MDS. All predefined RRTs were significantly lower in patients of the Cy-Flu-ATG arm (23.3 vs. 55.0 %; p = 0.003). Infection with identified causative organism and sinusoidal obstruction syndrome, hematuria, febrile episodes, and death from any cause tended to be more frequent in Cy-ATG arm but did not differ significantly between arms. There was no difference in neutrophil engraftment failure (2.5 vs. 2.33 %; p = 0.959), acute graft-versus-host disease (GvHD) (15.0 vs. 23.3 %; p = 0.388), and chronic GvHD (16.7 vs. 16.2 %; p = 0.961) between Cy-ATG and Cy-Flu-ATG arms. The 4-year survival rate did not differ between the Cy-ATG and Cy-Flu-ATG arms. Preconditioning with Cy-Flu-ATG was superior to that afforded by Cy-ATG in terms of reducing RRT levels without increasing engraftment failure. (ClinicalTrials.gov number: NCT01145976)

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Acknowledgments

We thank all members of the Cooperative Study Group A for Hematology and Ye Eun Jang and Mi Young Kim for assistance. This work was supported by Priority Research Center Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2010-0029621).

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Authors and Affiliations

  1. Division of Hematology-Oncology, Ulsan University Hospital University of Ulsan College of Medicine, Ulsan, Republic of Korea

    Hawk Kim & Jae-Hoo Park

  2. Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul, 138-736, Republic of Korea

    Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim & Kyoo-Hyung Lee

  3. Haeundae Paik Hospital, Busan, Republic of Korea

    Young-Don Joo

  4. Daegu Catholic University Hospital, Daegu, Republic of Korea

    Sung Hwa Bae & Hun Mo Ryoo

  5. Yeungnam University Hospital, Daegu, Republic of Korea

    Myung Soo Hyun & Min Kyoung Kim

  6. Busan Paik Hospital, Busan, Republic of Korea

    Won-Sik Lee

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  1. Hawk Kim
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Cooperative Study Group A for Hematology (COSAH)

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Correspondence to Kyoo-Hyung Lee.

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Kim, H., Lee, JH., Joo, YD. et al. A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome. Ann Hematol 91, 1459–1469 (2012). https://doi.org/10.1007/s00277-012-1462-x

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  • DOI: https://doi.org/10.1007/s00277-012-1462-x

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