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Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia.
Biol Blood Marrow Transplant. 2014 Apr; 20(4):549-55.BB

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], 18 second 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 14 g/m(2)/day treosulfan i.v. on days -6 to -4, 30 mg/m(2)/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 30 months, 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 2 years, 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.

Authors+Show Affiliations

Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington. Electronic address: bgyurkoc@fhcrc.org.Department of Medicine, University of Colorado, Denver, Colorado.Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Medac GmbH, Hamburg, Germany.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Department of Laboratory Medicine, University of Washing School of Medicine, Seattle, WA.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24440648

Citation

Gyurkocza, Boglarka, et al. "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 : Journal of the American Society for Blood and Marrow Transplantation, vol. 20, no. 4, 2014, pp. 549-55.
Gyurkocza B, Gutman J, Nemecek ER, et al. Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(4):549-55.
Gyurkocza, B., Gutman, J., Nemecek, E. R., Bar, M., Milano, F., Ramakrishnan, A., Scott, B., Fang, M., Wood, B., Pagel, J. M., Baumgart, J., Delaney, C., Maziarz, R. T., Sandmaier, B. M., Estey, E. H., Appelbaum, F. R., Storer, B. E., & Deeg, H. J. (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 : Journal of the American Society for Blood and Marrow Transplantation, 20(4), 549-55. https://doi.org/10.1016/j.bbmt.2014.01.009
Gyurkocza B, et al. Treosulfan, Fludarabine, and 2-Gy Total Body Irradiation Followed By Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2014;20(4):549-55. PubMed PMID: 24440648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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 R, 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 T, AU - Sandmaier,Brenda M, AU - Estey,Elihu H, AU - Appelbaum,Frederick R, AU - Storer,Barry E, AU - Deeg,Hans Joachim, Y1 - 2014/01/16/ PY - 2013/10/24/received PY - 2014/01/10/accepted PY - 2014/1/21/entrez PY - 2014/1/21/pubmed PY - 2014/11/5/medline KW - AML KW - Allogeneic hematopoietic cell transplantation KW - MDS KW - Total body irradiation KW - Treosulfan SP - 549 EP - 55 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 20 IS - 4 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], 18 second 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 14 g/m(2)/day treosulfan i.v. on days -6 to -4, 30 mg/m(2)/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 30 months, 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 2 years, 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. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/24440648/Treosulfan_fludarabine_and_2_Gy_total_body_irradiation_followed_by_allogeneic_hematopoietic_cell_transplantation_in_patients_with_myelodysplastic_syndrome_and_acute_myeloid_leukemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(14)00025-1 DB - PRIME DP - Unbound Medicine ER -