title: Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation.
abstract: Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m2and treosulfan 42 g/m2(FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m2to 180 mg/m2, busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece. Electronic address: bmt@gpapanikolaou.gr.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sakellari
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Despina
authors.initials: D
authors.lastname: Mallouri
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Gavriilaki
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Batsis
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kaliou
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Varnavas
authors.initials: V
authors.lastname: Constantinou
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Apostolia
authors.initials: A
authors.lastname: Papalexandri
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Chrysavgi
authors.initials: C
authors.lastname: Lalayanni
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Vadikolia
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Athanasiadou
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Yannaki
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Damianos
authors.initials: D
authors.lastname: Sotiropoulos
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Smias
authors.affiliation: Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D046528:Chimerism; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity
chemical_list: C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Allogeneic hematopoietic stem cell transplantation; Myeloid malignancies; Reduced-intensity conditioning; Reduced-toxicity conditioning