title: Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia.
abstract: Sequential use of chemotherapy and reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (SCT) has been proposed to improve the treatment outcomes in patients with high-risk acute myeloid leukemia (AML). Here, we present our experience with this procedure in a cohort of 60 AML patients with primary induction failure (n = 9); early, refractory, or ≥ second relapse (n = 41); or unfavorable cytogenetics (n = 10). A combination of fludarabine (30 mg/m²/day), cytarabine (2 g/m²/day), and amsacrine (100 mg/m²/day) for 4 days was used. After 3 days of rest, RIC was carried out, consisting of 4 Gy total body irradiation, antithymocyte globulin (ATG-Fresenius), and cyclophosphamide (fludarabine, amsacrine, and cytarabine (FLAMSA)-RIC protocol). Prophylactic donor lymphocyte infusions (pDLIs) were given in patients with complete remission (CR) and without evidence of graft-versus-host disease ≥120 days after SCT. The median time of neutrophil engraftment was 17 days. CR was achieved in 47 of 60 patients (78%). Eleven patients received pDLIs resulting in long-term CR in eight of them. Non-relapse mortality after 1 and 3 years was 25 and 28%, respectively. With a median follow-up of 37 months (range, 10-69), 3-year overall survival and 3-year progression-free survival were 42 and 33%, respectively. In a multivariate analysis, dose of CD34(+) cells >5 × 10⁶/kg (p = 0.005; hazard ratio (HR) = 0.276), remission of AML before SCT (p = 0.044; HR = 0.421), and achievement of complete chimerism after SCT (p = 0.001; HR = 0.205) were significant factors of better overall survival. The use of the FLAMSA-RIC protocol in suitable high-risk AML patients results in a long-term survival rate of over 40%.
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic. mkrejci@fnbrno.cz
authors.forename: Marta
authors.initials: M
authors.lastname: Krejci
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Dusek
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Racil
authors.forename: Milan
authors.initials: M
authors.lastname: Navratil
authors.forename: Miroslav
authors.initials: M
authors.lastname: Tomiska
authors.forename: Ondrej
authors.initials: O
authors.lastname: Horky
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000677:Amsacrine / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D003561:Cytarabine / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D000677:Amsacrine; D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine