title: Intermediate intensity conditioning regimen containing FLAMSA, treosulfan, cyclophosphamide, and ATG for allogeneic stem cell transplantation in elderly patients with relapsed or high-risk acute myeloid leukemia.
abstract: Lower dosage of total body irradiation (TBI) and chemotherapy in reduced-intensity conditioning (RIC) regimens prior to allogeneic stem cell transplantation have reduced the toxicity of the conditioning and non-relapse mortality. The FLAMSA-RIC protocol for high-risk patients with acute myeloid leukemia (AML) and myelodysplastic syndrome has shown promising results in refractory disease as well as in first complete remission. Still, the RIC protocol containing 4 Gy TBI/cyclophosphamide/anti-thymocyte globulin (ATG) implicates acute toxicity mainly due to TBI preventing its usage in patients with advanced age and/or severe co-morbidities. To increase feasibility and safety of the conditioning, we substituted TBI with treosulfan. Seventeen patients with relapsed or high-risk AML and either advanced age or concomitant disease were treated within a preparative regimen containing a 4-day course of chemotherapy (FLAMSA) followed by RIC comprising of treosulfan, cyclophosphamide, and ATG. After median follow-up of 12 months, the estimated incidences of relapse and non-relapse mortality were 25% and 20%, respectively. One-year overall survival was 62%. In conclusion, FLAMSA-treosulfan/cyclophosphamide/ATG is an intermediate intensity conditioning regimen with acceptable non-relapse mortality for patients with relapsed or high-risk AML. Substituting TBI with treosulfan provides an alternative to treat elderly patients or patients with severe co-morbidities when TBI appears not feasible due to the potential of increased toxicity.
authors.affiliation: BMT Program, Department I of Internal Medicine, University of Cologne, Kerpener Straße 62, 50924 Köln, Germany. jens.chemnitz@uk-koeln.de
authors.forename: Jens Marcus
authors.initials: JM
authors.lastname: Chemnitz
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Udo
authors.initials: U
authors.lastname: Holtick
authors.forename: Sebastian
authors.initials: S
authors.lastname: Theurich
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.forename: Anke
authors.initials: A
authors.lastname: Krause
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000961:Antilymphocyte Serum; D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; C018404:treosulfan; D002066:Busulfan