title: The impact of category, cytopathology and cytogenetics on development and progression of clonal and malignant myeloid transformation in inherited bone marrow failure syndromes.
abstract: Inherited bone marrow failure syndromes are a group of rare, heterogeneous genetic disorders with a risk of clonal and malignant myeloid transformation including clonal marrow cytogenetic abnormalities, myelodysplastic syndrome and acute myeloid leukemia. The clinical characteristics, risk classification, prognostic factors and outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes are largely unknown. The aims of this study were to determine the impact of category, cytopathology and cytogenetics, the three components of the "Category Cytology Cytogenetics" classification of pediatric myelodysplastic syndrome, on the outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure. We used data from the Canadian Inherited Marrow Failure Registry. Among 327 patients with inherited bone marrow failure syndrome enrolled in the registry, the estimated risk of clonal and malignant myeloid transformation by the age of 18 years was 37%. The risk of clonal and malignant myeloid transformation varied according to the type of inherited bone marrow failure syndrome but was highest in Fanconi anemia. The development of clonal and malignant myeloid transformation significantly affected overall survival. Mortality varied based on cytopathological group. The largest group of patients had refractory cytopenia. Clonal marrow cytogenetic abnormalities were identified in 87% of patients with clonal and malignant myeloid transformation, and different cytogenetic groups had different impacts on disease progression. We conclude that category, cytopathology and cytogenetics in cases of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes have an important impact on outcome and that the classification of such cases should incorporate these factors.
authors: Marrow Failure and Myelodysplasia Program, Division of Haematology/Oncology, Department of Paediatrics and the Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
authors: Michaela
authors: M
authors: Cada
authors: Marrow Failure and Myelodysplasia Program, Division of Haematology/Oncology, Department of Paediatrics and the Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
authors: Catherin I
authors: CI
authors: Segbefia
authors: Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors: Robert
authors: R
authors: Klaassen
authors: IWK Health Centre, Halifax, Nova Scotia, Canada.
authors: Conrad V
authors: CV
authors: Fernandez
authors: CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors: Rochelle A
authors: RA
authors: Yanofsky
authors: British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors: John
authors: J
authors: Wu
authors: Hôpital Ste. Justine, Montréal, Québec, Canada.
authors: Yves
authors: Y
authors: Pastore
authors: Queen's University, Kingston, Ontario, Canada.
authors: Mariana
authors: M
authors: Silva
authors: Princess Margaret Hospital, Toronto, Ontario, Canada.
authors: Jeffrey H
authors: JH
authors: Lipton
authors: Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
authors: Josee
authors: J
authors: Brossard
authors: Centre Hospital University Quebec-Pav CHUL, Sainte-Foy, Quebec, Canada.
authors: Bruno
authors: B
authors: Michon
authors: Montreal Children's Hospital, Montreal, Québec, Canada.
authors: Sharon
authors: S
authors: Abish
authors: Alberta Children's Hospital, Calgary, Alberta, Canada.
authors: MacGregor
authors: M
authors: Steele
authors: University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Roona
authors: R
authors: Sinha
authors: University of Alberta/Health Sciences Centre, Edmonton, Alberta, Canada.
authors: Mark
authors: M
authors: Belletrutti
authors: McMaster Children's Hospital/McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
authors: Vicky
authors: V
authors: Breakey
authors: Children's Hospital of Western Ontario, London, Ontario, Canada.
authors: Lawrence
authors: L
authors: Jardine
authors: Janeway Child Health Centre, St. John's, Newfoundland, Canada.
authors: Lisa
authors: L
authors: Goodyear
authors: The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Lillian
authors: L
authors: Sung
authors: Division of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Mary
authors: M
authors: Shago
authors: Program in Population Genomics, Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
authors: Joseph
authors: J
authors: Beyene
authors: Marrow Failure and Myelodysplasia Program, Division of Haematology/Oncology, Department of Paediatrics and the Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
authors: Preeti
authors: P
authors: Sharma
authors: Marrow Failure and Myelodysplasia Program, Division of Haematology/Oncology, Department of Paediatrics and the Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
authors: Bozana
authors: B
authors: Zlateska
authors: Marrow Failure and Myelodysplasia Program, Division of Haematology/Oncology, Department of Paediatrics and the Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children and the University of Toronto, Ontario, Canada yigal.dror@sickkids.ca.
authors: Yigal
authors: Y
authors: Dror
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic; D001853:Bone Marrow / Q000473:pathology; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D002170:Canada / Q000453:epidemiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D060965:Clonal Evolution; D020732:Cytogenetic Analysis; D018450:Disease Progression; D006457:Hemoglobinuria, Paroxysmal / Q000151:congenital* / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D063868:Patient Outcome Assessment; D011379:Prognosis; D012042:Registries; D012306:Risk; D055815:Young Adult