title: Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study.
abstract: BACKGROUND
  Allogeneic stem-cell transplantation (HSCT) is the only curative treatment in myelodysplastic syndromes (MDS). Azacitidine (AZA) is increasingly used prior to HSCT, however in Europe it is only approved for patients who are not eligible for HSCT.
  
  
  METHODS
  We conducted a phase II multicenter study to prospectively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome (MDS), 19 with acute myeloid leukemia (AML), and 8 with chronic myelomonocytic leukemia (CMML). After a median of four cycles (range 1-11): 24% of patients achieved complete remission, 14% partial remission, 8% hematologic improvement, 32% had stable and 22% progressive disease. Ten patients discontinued treatment before the planned four cycles, due to an adverse event in nine cases.
  
  
  RESULTS
  A HSC donor was identified in 73 patients, and HSCT was performed in 54 patients (74% of patients with a donor). Main reasons for turning down HSCT were lack of a donor, an adverse event, or progressive disease (9, 12, and 16 patients, respectively). At a median follow-up of 20.5 months from enrolment, response to AZA was the only independent prognostic factor for survival. Compared to baseline assessment, AZA treatment did not affect patients' comorbidities at HSCT: the HCT-CI remained stable in 62% patients, and worsened or improved in 23% and 15% of patients, respectively.
  
  
  CONCLUSIONS
  Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment. As matched unrelated donor was the most frequent source of donor cells, the time between diagnosis and HSCT needed for donor search could be 'bridged' using azacitidine. These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS. The trial has been registered with the EudraCT number 2010-019673-1.
authors.affiliation: Division of Hematology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome.
authors.forename: M T
authors.initials: MT
authors.lastname: Voso
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome.
authors.forename: G
authors.initials: G
authors.lastname: Leone
authors.affiliation: Department of Statistical Sciences, La Sapienza University, Rome.
authors.forename: A
authors.initials: A
authors.lastname: Piciocchi
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome.
authors.forename: L
authors.initials: L
authors.lastname: Fianchi
authors.affiliation: Department of Hematology, Centro Trapianti Midollo Osseo, Pescara.
authors.forename: S
authors.initials: S
authors.lastname: Santarone
authors.affiliation: Division of Hematology and BMT, Department of Experimental and Clinical Medical Sciences, Azienda Ospedaliero-Universitaria di Udine, Udine.
authors.forename: A
authors.initials: A
authors.lastname: Candoni
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome.
authors.forename: M
authors.initials: M
authors.lastname: Criscuolo
authors.affiliation: Department of Hematology, ASST Papa Giovanni XXIII, Bergamo.
authors.forename: A
authors.initials: A
authors.lastname: Masciulli
authors.affiliation: Department of Hematology, A.O. Spedali Civili, Brescia.
authors.forename: E
authors.initials: E
authors.lastname: Cerqui
authors.affiliation: Department of Hematology, Ospedale Niguarda, Milano.
authors.forename: A
authors.initials: A
authors.lastname: Molteni
authors.affiliation: Department of Hematology, Ospedale Sant'Orsola Malpighi, University of Bologna, Bologna.
authors.forename: C
authors.initials: C
authors.lastname: Finelli
authors.affiliation: Department of Hematology, HSCT Adult Unit, San Gerardo Hospital, Monza.
authors.forename: M
authors.initials: M
authors.lastname: Parma
authors.affiliation: Department of Hematology, Azienda Ospedaliera Universitaria - Ospedali Riuniti di Ancona, Ancona.
authors.forename: A
authors.initials: A
authors.lastname: Poloni
authors.affiliation: Department of Hematology, Ospedale Opera Padre Pio, San Giovanni Rotondo.
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.affiliation: Department of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: F
authors.initials: F
authors.lastname: Spina
authors.affiliation: Department of Hematology Oncology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milano.
authors.forename: A
authors.initials: A
authors.lastname: Cortelezzi
authors.affiliation: Department of Hematology, "SS Antonio e Biagio" Hospital, Alessandria.
authors.forename: F
authors.initials: F
authors.lastname: Salvi
authors.affiliation: Department of Hematology, Policlinico San Matteo and Pavia University, Pavia, Italy.
authors.forename: E P
authors.initials: EP
authors.lastname: Alessandrino
authors.affiliation: Department of Hematology, ASST Papa Giovanni XXIII, Bergamo.
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
authors.affiliation: Department of Hematology, Università Cattolica del Sacro Cuore, Rome.
authors.forename: S
authors.initials: S
authors.lastname: Sica
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001374:Azacitidine / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007558:Italy; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015477:Leukemia, Myelomonocytic, Chronic / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
keywords: allogeneic stem-cell transplantation; azacitidine; high-risk MDS; hypomethylating treatment