title: Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia.
abstract: BACKGROUND
  The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI).
  
  
  METHODS
  Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT.
  
  
  RESULTS
  The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001).
  
  
  CONCLUSIONS
  This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Yi
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Xiong
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Liu
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lyu
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Shi-Zhen
authors.initials: SZ
authors.lastname: Zhong
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: De-Hui
authors.initials: DH
authors.lastname: Zou
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Gang
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Zeng-Jun
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300041, China.
authors.forename: Lu-Gui
authors.initials: LG
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis
chemical_list: D007143:Immunoglobulin Heavy Chains