title: Age influences initial dose and compliance to imatinib in chronic myeloid leukemia elderly patients but concomitant comorbidities appear to influence overall and event-free survival.
abstract: We applied Charlson comorbidity index (CCI) stratification on a large cohort of chronic myeloid leukemia (CML) very elderly patients (>75 years) treated with imatinib, in order to observe the impact of concomitant diseases on both compliance and outcome. One hundred and eighty-one patients were recruited by 21 Italian centers. There were 95 males and 86 females, median age 78.6 years (range 75-93.6). According to Sokal score, 106 patients were classified as intermediate risk and 55 as high risk (not available in 20 patients). According to CCI stratification, 71 patients had score 0 and 110 a score ≥ 1. Imatinib standard dose was reduced at start of therapy (200-300 mg/day) in 68 patients independently from the evaluation of baseline comorbidities, but based only on physician judgement: 43.6% of these patients had score 0 compared to 34% of patients who had score ≥ 1. Significant differences were found in terms of subsequent dose reduction (39% of patients with score 0 compared to 53% of patients with score ≥ 1) and in terms of drug discontinuation due to toxicity (35% of patients with score 0 vs 65% of patients with score ≥ 1). We did not find significant differences as regards occurrence of hematologic side effects, probably as a consequence of the initial dose reduction: 39% of patients with score 0 experienced grade 3/4 hematologic toxicity (most commonly anemia) compared to 42% of patients with score ≥ 1. Independently from the initial dose, comorbidities again did not have an impact on development of grade 3/4 non-hematologic side effects (most commonly skin rash, muscle cramps and fluid retention): 62% of patients with score 0 compared to 52.5% of patients with score ≥ 1. Notwithstanding the reduced dose and the weight of comorbidities we did not find significant differences but only a trend in terms of efficacy: 66% of patients with score 0 achieved a CCyR compared to 54% of patients with score ≥ 1. Comorbidities appeared to have an impact on median OS (40.8 months for patients with score 0 vs 20.16 months for patients with score ≥ 1) on EFS and on non-CML death rate. Our results suggest that treatment of very elderly CML patients might be influenced by personal physician perception: evaluation at baseline of comorbidities according to CCI should improve initial decision-making in this subset of patients.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università "La Sapienza", Via Benevento 6, Roma 00161, Italy. Electronic address: breccia@bce.uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Ematologia, Università "Federico II", Napoli, Italy.
authors.forename: Luigiana
authors.initials: L
authors.lastname: Luciano
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università "La Sapienza", Via Benevento 6, Roma 00161, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.affiliation: Ematologia, Università di Bologna, Bologna, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Ematologia, Università di Torino, Torino, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Ferrero
authors.affiliation: Ematologia, Università di Ferrara, Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.affiliation: Ematologia, Ospedale Sant'Eugenio, Roma, Italy.
authors.forename: Malgorzata Monica
authors.initials: MM
authors.lastname: Trawinska
authors.affiliation: Ematologia, Ospedale Cardarelli, Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Annunziata
authors.affiliation: Ematologia, Ospedale Ferrarotto, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: Ematologia, Università di Udine, Udine, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.affiliation: Ematologia, Università di Padova, Padova, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Binotto
authors.affiliation: Ematologia, Università di Torino, Torino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Crisà
authors.affiliation: Dipartimento Onco-Ematologico, IRCCS-CROB, Rionero in Vulture, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Ematologia, Università di Firenze, Firenze, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Gozzini
authors.affiliation: Ematologia, Università di Perugia, Perugia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cavalli
authors.affiliation: Ematologia, Ospedale Sant'Andrea, Roma, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Montefusco
authors.affiliation: UOC Oncoematologia, Fondazione IRCSS Cà Granda Policlinico Milano, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.affiliation: Ematologia, Università di Messina, Messina, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Russo
authors.affiliation: Ematologia, Ospedale S. Giovanni, Roma, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cedrone
authors.affiliation: Ematologia con Trapianto, Università di Bari, Bari, Italy.
authors.forename: Antonella Russo
authors.initials: AR
authors.lastname: Rossi
authors.affiliation: Ematologia, Ospedale S Giovanni Battista, Torino, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pregno
authors.affiliation: Ematologia, Centro Trapianti Cremona, Cremona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Endri
authors.affiliation: Ematologia, IFO Regina Elena, Roma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Spadea
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università "La Sapienza", Via Benevento 6, Roma 00161, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Molica
authors.affiliation: Ematologia, Ospedale Civile di Campobasso, Campobasso, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Giglio
authors.affiliation: Ematologia, Ospedale Belcolle, Viterbo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Celesti
authors.affiliation: Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sorà
authors.affiliation: Onco-Ematologia, Università Cattolica Giovanni Paolo II, Campobasso, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Storti
authors.affiliation: Ematologia, Ospedale Villa S Pietro, Roma, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: D'Addosio
authors.affiliation: Ematologia, Polo Universitario ASO San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Giovanna Rege
authors.initials: GR
authors.lastname: Cambrin
authors.affiliation: Ematologia, Pesaro, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Isidori
authors.affiliation: Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.affiliation: Ematologia, Ospedale Sant'Eugenio, Roma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.affiliation: Ematologia con Trapianto, Università di Bari, Bari, Italy.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Speccha
authors.affiliation: Ematologia, Università di Bologna, Bologna, Italy.
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università "La Sapienza", Via Benevento 6, Roma 00161, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D015897:Comorbidity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D055118:Medication Adherence; D010879:Piperazines / Q000627:therapeutic use*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Age; Chronic myeloid leukemia; Comorbidities; Overall survival