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. 2016 Oct;22(10):1792-1800.
doi: 10.1016/j.bbmt.2016.06.023. Epub 2016 Jul 1.

Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome

Gheath Alatrash  1 , Peter F Thall  2 , Benigno C Valdez  1 , Patricia S Fox  2 , Jing Ning  2 , Haven R Garber  1 , Selma Janbey  1 , Laura L Worth  3 , Uday Popat  1 , Chitra Hosing  1 , Amin M Alousi  1 , Partow Kebriaei  1 , Elizabeth J Shpall  1 , Roy B Jones  1 , Marcos de Lima  4 , Gabriela Rondon  1 , Julianne Chen  1 , Richard E Champlin  1 , Borje S Andersson  5
Affiliations

Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome

Gheath Alatrash et al. Biol Blood Marrow Transplant. 2016 Oct.

Abstract

Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group.

Keywords: Allogeneic stem cell transplantation; Busulfan; Clofarabine; Conditioning regimen; Fludarabine.

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Figures

Figure 1
Figure 1
OS by treatment arm for the entire cohort (A), patients in CR (B) or with active disease (C).
Figure 2
Figure 2
PFS by treatment arm for the entire cohort (A), patients in CR (B) or with active disease (C).
Figure 3
Figure 3
OS (left) and PFS (right) for patients with AML/MDS by treatment arm (A and B) and combined arms (C and D).
See this image and copyright information in PMC

References

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