title: Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation.
abstract: Advanced myelodysplastic syndrome harbors a high risk of progression to acute myeloid leukemia and poor prognosis. In children, there is no established treatment to prevent or delay progression to leukemia prior to hematopoietic stem cell transplantation. Azacitidine is a hypomethylating agent, which was shown to slow progression to leukemia in adults with myelodysplastic syndrome. There is little data on the efficacy of azacitidine in children. We reviewed 22 pediatric patients with advanced myelodysplastic syndrome from a single center, diagnosed between January 2000 and December 2015. Of those, eight patients received off-label azacitidine before hematopoietic stem cell transplantation. A total of 31 cycles were administered and modification or delay occurred in four of them due to cytopenias, infection, nausea/vomiting, and transient renal impairment. Bone marrow blast percentages in azacitidine-treated patients decreased significantly from a median of 15% (range 9-31%) at the start of treatment to 5.5% (0-12%, P=0.02) before hematopoietic stem cell transplantation. Following azacitidine treatment, four patients (50%) achieved marrow remission, and none progressed. In contrast, three untreated patients (21.4%) had progressive disease characterized by >50% increase in blast counts or progression to leukemia. Azacitidine-treated patients had significantly increased 4-year event-free survival (P=0.04); predicted 4-year overall survival was 100% versus 69.3% in untreated patients (P=0.1). In summary, azacitidine treatment prior to hematopoietic stem cell transplantation was well tolerated in pediatric patients with advanced myelodysplastic syndrome, led to partial or complete bone marrow response in seven of eight patients (87.5%), and correlated with superior event-free survival in this cohort.
authors.affiliation: Marrow Failure and Myelodysplasia Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.|Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Waespe
authors.affiliation: Marrow Failure and Myelodysplasia Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.|Pediatric Hematology/Oncology, UZ Brussel, Jette, Belgium.
authors.forename: Machiel
authors.initials: M
authors.lastname: Van Den Akker
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Klaassen
authors.affiliation: Department of Laboratory Medicine, University Health Network, Toronto, Canada.
authors.forename: Lani
authors.initials: L
authors.lastname: Lieberman
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Irwin
authors.affiliation: Bone Marrow Transplantation Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Salah S
authors.initials: SS
authors.lastname: Ali
authors.affiliation: Department of Pediatric Laboratory Medicine, Division of Hematopathology, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelhaleem
authors.affiliation: Marrow Failure and Myelodysplasia Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.|Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Bozana
authors.initials: B
authors.lastname: Zlateska
authors.affiliation: Marrow Failure and Myelodysplasia Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Mira
authors.initials: M
authors.lastname: Liebman
authors.affiliation: Marrow Failure and Myelodysplasia Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Michaela
authors.initials: M
authors.lastname: Cada
authors.affiliation: Bone Marrow Transplantation Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Tal
authors.initials: T
authors.lastname: Schechter
authors.affiliation: Marrow Failure and Myelodysplasia Program, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada yigal.dror@sickkids.ca.|Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Yigal
authors.initials: Y
authors.lastname: Dror
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D011300:Preoperative Care; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine