Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia

Boglarka Gyurkocza, Jonathan Gutman, Eneida Nemecek, Merav Bar, Filippo Milano, Aravind Ramakrishnan, Bart Scott, Min Fang, Brent Wood, John M. Pagel, Joachim Baumgart, Colleen Delaney, Richard Maziarz, Brenda M. Sandmaier, Elihu H. Estey, Frederick R. Appelbaum, Barry E. Storer, Hans Joachim Deeg

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n=60: 35 first complete remission [CR], 18second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14g/m2/day treosulfan i.v. on days-6 to-4, 30mg/m2/day fludarabine i.v. on days-6 to-2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS (41% versus 79%) at 2years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.

Original languageEnglish (US)
Pages (from-to)549-555
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number4
DOIs
StatePublished - 2014

Fingerprint

treosulfan
Whole-Body Irradiation
Myelodysplastic Syndromes
Cell Transplantation
Acute Myeloid Leukemia
Recurrence
Cytogenetics
Refractory Anemia with Excess of Blasts
Incidence
Graft vs Host Disease
Survival
fludarabine
Leukemia, Myelomonocytic, Chronic

Keywords

  • Allogeneic hematopoietic cell transplantation
  • AML
  • MDS
  • Total body irradiation
  • Treosulfan

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia. / Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M.; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard; Sandmaier, Brenda M.; Estey, Elihu H.; Appelbaum, Frederick R.; Storer, Barry E.; Deeg, Hans Joachim.

In: Biology of Blood and Marrow Transplantation, Vol. 20, No. 4, 2014, p. 549-555.

Research output: Contribution to journalArticle

Gyurkocza, B, Gutman, J, Nemecek, E, Bar, M, Milano, F, Ramakrishnan, A, Scott, B, Fang, M, Wood, B, Pagel, JM, Baumgart, J, Delaney, C, Maziarz, R, Sandmaier, BM, Estey, EH, Appelbaum, FR, Storer, BE & Deeg, HJ 2014, 'Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia', Biology of Blood and Marrow Transplantation, vol. 20, no. 4, pp. 549-555. https://doi.org/10.1016/j.bbmt.2014.01.009
Gyurkocza, Boglarka ; Gutman, Jonathan ; Nemecek, Eneida ; Bar, Merav ; Milano, Filippo ; Ramakrishnan, Aravind ; Scott, Bart ; Fang, Min ; Wood, Brent ; Pagel, John M. ; Baumgart, Joachim ; Delaney, Colleen ; Maziarz, Richard ; Sandmaier, Brenda M. ; Estey, Elihu H. ; Appelbaum, Frederick R. ; Storer, Barry E. ; Deeg, Hans Joachim. / Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia. In: Biology of Blood and Marrow Transplantation. 2014 ; Vol. 20, No. 4. pp. 549-555.
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abstract = "Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n=60: 35 first complete remission [CR], 18second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14g/m2/day treosulfan i.v. on days-6 to-4, 30mg/m2/day fludarabine i.v. on days-6 to-2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73{\%}, 27{\%}, and 8{\%}, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59{\%} (10{\%}) and 47{\%}, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69{\%} and 85{\%}, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64{\%} and 76{\%}, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70{\%} versus 18{\%}) and lower OS (41{\%} versus 79{\%}) at 2years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.",
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T1 - Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia

AU - Gyurkocza, Boglarka

AU - Gutman, Jonathan

AU - Nemecek, Eneida

AU - Bar, Merav

AU - Milano, Filippo

AU - Ramakrishnan, Aravind

AU - Scott, Bart

AU - Fang, Min

AU - Wood, Brent

AU - Pagel, John M.

AU - Baumgart, Joachim

AU - Delaney, Colleen

AU - Maziarz, Richard

AU - Sandmaier, Brenda M.

AU - Estey, Elihu H.

AU - Appelbaum, Frederick R.

AU - Storer, Barry E.

AU - Deeg, Hans Joachim

PY - 2014

Y1 - 2014

N2 - Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n=60: 35 first complete remission [CR], 18second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14g/m2/day treosulfan i.v. on days-6 to-4, 30mg/m2/day fludarabine i.v. on days-6 to-2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS (41% versus 79%) at 2years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.

AB - Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n=60: 35 first complete remission [CR], 18second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14g/m2/day treosulfan i.v. on days-6 to-4, 30mg/m2/day fludarabine i.v. on days-6 to-2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS (41% versus 79%) at 2years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.

KW - Allogeneic hematopoietic cell transplantation

KW - AML

KW - MDS

KW - Total body irradiation

KW - Treosulfan

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