Allogeneic hematopoietic stem cell transplantation with fludarabine, busulfan, and thiotepa conditioning is associated with favorable outcomes in myelofibrosis

Roni Shouval, Yakov Vega, Joshua A. Fein, Ivetta Danylesko, Noga Shem Tov, Ronit Yerushalmi, Marta Sobas, Anna Czyż, Arnon Nagler, Avichai Shimoni

Research output: Contribution to journalArticle

Abstract

Allogeneic stem cell transplantation is a curative therapy for myelofibrosis. The optimal conditioning regimen has not been well defined. We retrospectively compared transplantation outcomes in patients with myelofibrosis (n = 67) conditioned with myeloablative (MAC, 36%) and reduced-intensity (RIC, 46%) regimens, and more recently with the combination of thiotepa, busulfan, and fludarabine (TBF, 18%). Patients were transplanted from HLA-matched sibling (n = 26) or unrelated donors (n = 41) between the years 2003 and 2018. The median follow-up was 2.9 years for all patients but shorter in the TBF group (1.1 years). The probability of 3-year progression-free survival (PFS) was 43%. At 1 year, the rate of PFS was 80%, 54%, and 45% with TBF, MAC, and RIC, respectively (p = 0.031). In a multivariable model, there was a greater risk for death with MAC (hazard ratio [HR] 12.26, p = 0.026) and lower PFS with both MAC (hazard ratio [HR] 7.78, p = 0.017) and RIC (HR 5.43, p = 0.027) compared with TBF. Relapse was higher with RIC (HR 8.20, p = 0.043) while nonrelapse mortality was increased with MAC (HR 9.63 p = 0.049). Our results indicate that TBF is a promising preparative regimen in myelofibrosis patients transplanted from matched sibling or unrelated donors, and should be further explored.

Original languageEnglish (US)
Pages (from-to)147-156
Number of pages10
JournalBone marrow transplantation
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2020

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Thiotepa
Busulfan
Primary Myelofibrosis
Hematopoietic Stem Cell Transplantation
Disease-Free Survival
Unrelated Donors
Siblings
Stem Cell Transplantation
Transplantation
Recurrence
Mortality
fludarabine
Conditioning (Psychology)

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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Allogeneic hematopoietic stem cell transplantation with fludarabine, busulfan, and thiotepa conditioning is associated with favorable outcomes in myelofibrosis. / Shouval, Roni; Vega, Yakov; Fein, Joshua A.; Danylesko, Ivetta; Shem Tov, Noga; Yerushalmi, Ronit; Sobas, Marta; Czyż, Anna; Nagler, Arnon; Shimoni, Avichai.

In: Bone marrow transplantation, Vol. 55, No. 1, 01.01.2020, p. 147-156.

Research output: Contribution to journalArticle

Shouval, Roni ; Vega, Yakov ; Fein, Joshua A. ; Danylesko, Ivetta ; Shem Tov, Noga ; Yerushalmi, Ronit ; Sobas, Marta ; Czyż, Anna ; Nagler, Arnon ; Shimoni, Avichai. / Allogeneic hematopoietic stem cell transplantation with fludarabine, busulfan, and thiotepa conditioning is associated with favorable outcomes in myelofibrosis. In: Bone marrow transplantation. 2020 ; Vol. 55, No. 1. pp. 147-156.
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abstract = "Allogeneic stem cell transplantation is a curative therapy for myelofibrosis. The optimal conditioning regimen has not been well defined. We retrospectively compared transplantation outcomes in patients with myelofibrosis (n = 67) conditioned with myeloablative (MAC, 36{\%}) and reduced-intensity (RIC, 46{\%}) regimens, and more recently with the combination of thiotepa, busulfan, and fludarabine (TBF, 18{\%}). Patients were transplanted from HLA-matched sibling (n = 26) or unrelated donors (n = 41) between the years 2003 and 2018. The median follow-up was 2.9 years for all patients but shorter in the TBF group (1.1 years). The probability of 3-year progression-free survival (PFS) was 43{\%}. At 1 year, the rate of PFS was 80{\%}, 54{\%}, and 45{\%} with TBF, MAC, and RIC, respectively (p = 0.031). In a multivariable model, there was a greater risk for death with MAC (hazard ratio [HR] 12.26, p = 0.026) and lower PFS with both MAC (hazard ratio [HR] 7.78, p = 0.017) and RIC (HR 5.43, p = 0.027) compared with TBF. Relapse was higher with RIC (HR 8.20, p = 0.043) while nonrelapse mortality was increased with MAC (HR 9.63 p = 0.049). Our results indicate that TBF is a promising preparative regimen in myelofibrosis patients transplanted from matched sibling or unrelated donors, and should be further explored.",
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AU - Vega, Yakov

AU - Fein, Joshua A.

AU - Danylesko, Ivetta

AU - Shem Tov, Noga

AU - Yerushalmi, Ronit

AU - Sobas, Marta

AU - Czyż, Anna

AU - Nagler, Arnon

AU - Shimoni, Avichai

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N2 - Allogeneic stem cell transplantation is a curative therapy for myelofibrosis. The optimal conditioning regimen has not been well defined. We retrospectively compared transplantation outcomes in patients with myelofibrosis (n = 67) conditioned with myeloablative (MAC, 36%) and reduced-intensity (RIC, 46%) regimens, and more recently with the combination of thiotepa, busulfan, and fludarabine (TBF, 18%). Patients were transplanted from HLA-matched sibling (n = 26) or unrelated donors (n = 41) between the years 2003 and 2018. The median follow-up was 2.9 years for all patients but shorter in the TBF group (1.1 years). The probability of 3-year progression-free survival (PFS) was 43%. At 1 year, the rate of PFS was 80%, 54%, and 45% with TBF, MAC, and RIC, respectively (p = 0.031). In a multivariable model, there was a greater risk for death with MAC (hazard ratio [HR] 12.26, p = 0.026) and lower PFS with both MAC (hazard ratio [HR] 7.78, p = 0.017) and RIC (HR 5.43, p = 0.027) compared with TBF. Relapse was higher with RIC (HR 8.20, p = 0.043) while nonrelapse mortality was increased with MAC (HR 9.63 p = 0.049). Our results indicate that TBF is a promising preparative regimen in myelofibrosis patients transplanted from matched sibling or unrelated donors, and should be further explored.

AB - Allogeneic stem cell transplantation is a curative therapy for myelofibrosis. The optimal conditioning regimen has not been well defined. We retrospectively compared transplantation outcomes in patients with myelofibrosis (n = 67) conditioned with myeloablative (MAC, 36%) and reduced-intensity (RIC, 46%) regimens, and more recently with the combination of thiotepa, busulfan, and fludarabine (TBF, 18%). Patients were transplanted from HLA-matched sibling (n = 26) or unrelated donors (n = 41) between the years 2003 and 2018. The median follow-up was 2.9 years for all patients but shorter in the TBF group (1.1 years). The probability of 3-year progression-free survival (PFS) was 43%. At 1 year, the rate of PFS was 80%, 54%, and 45% with TBF, MAC, and RIC, respectively (p = 0.031). In a multivariable model, there was a greater risk for death with MAC (hazard ratio [HR] 12.26, p = 0.026) and lower PFS with both MAC (hazard ratio [HR] 7.78, p = 0.017) and RIC (HR 5.43, p = 0.027) compared with TBF. Relapse was higher with RIC (HR 8.20, p = 0.043) while nonrelapse mortality was increased with MAC (HR 9.63 p = 0.049). Our results indicate that TBF is a promising preparative regimen in myelofibrosis patients transplanted from matched sibling or unrelated donors, and should be further explored.

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