title: The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients.
abstract: The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL-IPI score stratified Binet stage A patients into three subgroups with different outcome. Since the CLL-IPI was originally developed to predict survival, we next investigated the optimal cut-off score to predict TTFT in Binet stage A patients. Recursive partitioning analysis identified three subsets with scores of 0 (n = 139), 1 (n = 90), and ≥ 2(n = 108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (P < 0.0001.; C-statistic:c = 0.72; 95% CI:0.58-0.81). This optimized CLL-IPI scoring for TTFT was subsequently validated in an independent cohort of Binet A patients from the Mayo Clinic (n = 525). The ability of either original or optimized CLL-IPI to predict TTFT was equivalent to other prognostic models specifically designed for this endpoint (2011 MDACC score and O-CLL1 score). Although originally developed to predict suvival, the CLL-IPI is useful for predicting TTFT in early stage CLL patients. Am. J. Hematol. 91:1090-1095, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Oncology and Hematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy. smolica@libero.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.affiliation: Department of Internal Medicine Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.affiliation: Biostatistics Unit, Regina Elena Institute for Cancer Research and Treatment, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Hematology Unit Department of Onco-Hematology, a.O. Of Cosenza, Cosenza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Department of Oncology and Hematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mirabelli
authors.affiliation: SS Molecular Diagnostics IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.affiliation: Department of Oncology and Hematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.affiliation: Hematology Unit, Ospedale Vito Fazzi, Lecce, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Renzo
authors.affiliation: Department of Biomedical Sciences Division of Haematology, University of Catania and Ferrarotto Hospital, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.affiliation: Division of Haematology, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.affiliation: Department of Hematology, Ospedale Santo Spirito, Pescara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angrilli
authors.affiliation: Division of Haematology, Arcispedale S. Maria Nuova/IRCCS, Reggio Emilia, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Famà
authors.affiliation: Biotechnology Research Unit, Azienda Sanitaria Provinciale Di Cosenza, Aprigliano, (CS, Italy).
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kari G
authors.identifier: http://orcid.org/0000-0002-7313-1875
authors.initials: KG
authors.lastname: Chaffee
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Milano, Italy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico.
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.affiliation: Department of Internal Medicine Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.affiliation: San Martino IST, Direzione Scientifica IRCCS, Genova, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.affiliation: Hematology Unit Department of Onco-Hematology, a.O. Of Cosenza, Cosenza, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007558:Italy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D061665:Time-to-Treatment
keywords: leukemia