Clofarabine-fludarabine-busulfan in HCT for pediatric leukemia: an effective, low toxicity, TBI-free conditioning regimen

A. Birgitta Versluijs, Coco C.H. de Koning, Arjan C. Lankester, Stefan Nierkens, Wouter J. Kollen, Dorine Bresters, Caroline A. Lindemans, Jaap Jan Boelens, Marc Bierings

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8 Citations (Scopus)


We prospectively studied clofarabine-fludarabine-busulfan (CloFluBu)-conditioning in allogeneic hematopoietic cell therapy (HCT) for lymphoid and myeloid malignancies and hypothesized that CloFluBu provides a less toxic alternative to conventional conditioning regimens, with adequate antileukemic activity. All patients receiving their first HCT, from 2011-2019, were included and received CloFluBu. The primary endpoint was event-free survival (EFS). Secondary endpoints were overall survival (OS), graft-versus-host disease (GvHD)-relapse-free survival (GRFS), treatment-related mortality (TRM), cumulative incidence of relapse (CIR), acute and chronic GvHD (aGvHD and cGvHD), and veno-occlusive disease (VOD). Cox proportional hazard and Fine and Gray competing-risk models were used for data analysis. One hundred fifty-five children were included: 60 acute lymphoid leukemia (ALL), 69 acute myeloid leukemia (AML), and 26 other malignancies (mostly MDS-EB). The median age was 9.7 (0.5 to 18.6) years. Estimated 2-year EFS was 72.0% ± 6.0 in ALL patients, and 62.4% ± 6.0 in AML patients. TRM in the whole cohort was 11.0% ± 2.6, incidence of aGvHD 3 to 4 at 6 months was 12.3% ± 2.7, extensive cGvHD at 2 years was 6.4% ± 2.1. Minimal residual disease-positivity prior to HCT was associated with higher CIR, both in ALL and AML. CloFluBu showed limited toxicity and encouraging EFS. CloFluBu is a potentially less toxic alternative to conventional conditioning regimens. Randomized prospective studies are needed.

Original languageEnglish
Pages (from-to)1719-1730
Number of pages12
JournalBlood Advances
Issue number6
Publication statusPublished - 22 Mar 2022


  • Busulfan/adverse effects
  • Child
  • Clofarabine
  • Graft vs Host Disease/pathology
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute/drug therapy
  • Recurrence
  • Vidarabine/analogs & derivatives


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