title: An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies.
abstract: Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.
authors.affiliation: Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Padron
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Patnaik
authors.affiliation: Service d'Hematologie, Hopital Avicenne, Bobigny, France.
authors.forename: R
authors.initials: R
authors.lastname: Itzykson
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lasho
authors.affiliation: Leukemia Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nazha
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Rampal
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Sanchez
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: E
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: N H
authors.initials: NH
authors.lastname: Al Ali
authors.affiliation: Department of Biostatistics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Thompson
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Colla
authors.affiliation: Service d'Hématologie Séniors, Hôpital St Louis, Université Paris 7, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
authors.forename: S
authors.initials: S
authors.lastname: Killick
authors.affiliation: Leukemia Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Sekeres
authors.affiliation: Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: List
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Onida
authors.affiliation: Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Komrokji
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.affiliation: Gustave Roussy, INSERM U1170, Villejuif, France.
authors.forename: E
authors.initials: E
authors.lastname: Solary
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066264:Datasets as Topic; D003663:Decision Trees; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012372:ROC Curve; D055815:Young Adult