title: Sequential chemotherapy followed by reduced-intensity conditioning and allogeneic haematopoietic stem cell transplantation in adult patients with relapse or refractory acute myeloid leukaemia: a survey from the Acute Leukaemia Working Party of EBMT.
abstract: This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%. The 3-year probability of non-relapse mortality (NRM) was 25·9%, that of relapse was 48·5%, that of GVHD-free and relapse-free survival (GRFS) was 17·8% and that of leukaemia-free survival (LFS) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II-IV [hazard ratio (HR) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti-T-cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti-T-cell antibodies seems promising in patients with refractory AML.
authors.affiliation: Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.|Hopital Saint-Antoine, AP-HP, Paris, France.|Universite Pierre & Marie Curie, Paris, France.|INSERM UMRs 938, CEREST-TC EBMT, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: II Medizinische Klinik, Klinikum Augsburg, Augsburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.affiliation: Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Behnam
authors.initials: B
authors.lastname: Sadeghi
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.|Hopital Saint-Antoine, AP-HP, Paris, France.|Universite Pierre & Marie Curie, Paris, France.|INSERM UMRs 938, CEREST-TC EBMT, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Polge
authors.affiliation: Med Klinik III, Klinikum Grosshadern, Munich, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tischer
authors.affiliation: Department of Haematology/Oncology, Hannover Medical University, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: BMT Unit, Hospital Herriot, Lyon, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Department of Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.affiliation: Department of Haematology, Oncology, and Immunology, Helios-Kliniken Berlin-Buch, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.affiliation: Chaim Sheba Medical Centre, Tel-Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.|Hopital Saint-Antoine, AP-HP, Paris, France.|Universite Pierre & Marie Curie, Paris, France.|INSERM UMRs 938, CEREST-TC EBMT, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D011795:Surveys and Questionnaires; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies
keywords: acute myeloid leukaemia; allogeneic haematopoietic stem cell transplantation; reduced intensity conditioning; sequential chemotherapy