The impact of category, cytopathology and cytogenetics on development and progression of clonal and malignant myeloid transformation in inherited bone marrow failure syndromes
Michaela Cada,
Catherin I. Segbefia,
Robert Klaassen,
Conrad V. Fernandez,
Rochelle A. Yanofsky,
John Wu,
Yves Pastore,
Mariana Silva,
Jeffrey H. Lipton,
Josee Brossard,
Bruno Michon,
Sharon Abish,
MacGregor Steele,
Roona Sinha,
Mark Belletrutti,
Vicky Breakey,
Lawrence Jardine,
Lisa Goodyear,
Lillian Sung,
Mary Shago,
Joseph Beyene,
Preeti Sharma,
Bozana Zlateska,
Yigal Dror
Affiliations
Michaela Cada
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
Catherin I. Segbefia
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
Robert Klaassen
Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Conrad V. Fernandez
IWK Health Centre, Halifax, Nova Scotia, Canada
Rochelle A. Yanofsky
CancerCare Manitoba, Winnipeg, Manitoba, Canada
John Wu
British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
Yves Pastore
Hôpital Ste. Justine, Montréal, Québec, Canada
Mariana Silva
Queen’s University, Kingston, Ontario, Canada
Jeffrey H. Lipton
Princess Margaret Hospital, Toronto, Ontario, Canada
Josee Brossard
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
Bruno Michon
Centre Hospital University Quebec-Pav CHUL, Sainte-Foy, Quebec, Canada
Sharon Abish
Montreal Children’s Hospital, Montreal, Québec, Canada
MacGregor Steele
Alberta Children’s Hospital, Calgary, Alberta, Canada
Roona Sinha
University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Mark Belletrutti
University of Alberta/Health Sciences Centre, Edmonton, Alberta, Canada
Vicky Breakey
McMaster Children’s Hospital/McMaster University Health Sciences Centre, Hamilton, Ontario, Canada
Lawrence Jardine
Children’s Hospital of Western Ontario, London, Ontario, Canada
Lisa Goodyear
Janeway Child Health Centre, St. John’s, Newfoundland, Canada
Lillian Sung
The Hospital for Sick Children, Toronto, Ontario, Canada
Mary Shago
Division of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
Joseph Beyene
Program in Population Genomics, Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Canada
Preeti Sharma
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
Bozana Zlateska
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
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
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.
