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
N1 - Funding Information:
Conflict of interest statement: This work was supported in part by research funding from Medac GmbH (Hamburg, Germany), the manufacturer of treosulfan. J.B. is an employee of Medac, GmbH (Hamburg, Germany). The authors have no other relevant financial disclosures to make.
PY - 2014/4
Y1 - 2014/4
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], 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 - AML
KW - Allogeneic hematopoietic cell transplantation
KW - MDS
KW - Total body irradiation
KW - Treosulfan
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UR - http://www.scopus.com/inward/citedby.url?scp=84895799081&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2014.01.009
DO - 10.1016/j.bbmt.2014.01.009
M3 - Article
C2 - 24440648
AN - SCOPUS:84895799081
SN - 1083-8791
VL - 20
SP - 549
EP - 555
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -