The Charlson comorbidities index (CCI) is a list of 19 conditions (including cardiologic, pulmonary diseases, diabetes, etc) with a weight assigned from 1 to 6, derived from relative risk estimates of a proportional hazard regression model using clinical data. Aims. We retrospectively evaluated the weight of CCI in a cohort of 125 elderly (> 60 years) chronic phase chronic myeloid leukemia (CP-CML) patients receiving dasatinib after imatinib resistance or intolerance. Methods. Score point 0 was assigned to 65 patients, whereas a score point >1 was assigned to 60 patients (35 patients =1, 19 patients= 2; 5 patients= 3; 1 patient= 4). Fifty-two patients received 70 mg twice daily and 56 patients received 100 mg once daily, in accordance with the results of the phase III trial, whereas 17 patients started with a dose less than 100 mg. Results. We found a significant association between CCI and drug reduction or suspension rate: during dasatinib treatment 49% of score 0 patients experienced a reduction of the dose compared to 63% of patients with score 1, 74% of patients with score 2 and 100% of patients with score 3 and 5 (P=0.03). Of the 65 patients with score 0, 29% had at least one suspension (79% for haematologic and 21% for non-hematologic toxicity, respectively), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-haematologic toxicity) and 100% of patients with score 3 and 4 (all patients for both types of toxicity) (P=0.003). Forty-one patients (32.8%) experienced pleural effusion during treatment: of these, 17 patients (26%) had score = 0, 13 patients (40%) score=1, 8 (42%) score=2 and 3 (60%) had score 3-4 (P=0.002). More pleural effusions occurred in patients who had score > 0 and who received higher dasatinib dose (140 mg). Nine patients experienced grade 3 and 31 patients grade 1-2 effusions: although the incidence of this event correlated with CCI stratification and dose received, its severity did not show the same correlation. Summary. In conclusion, in elderly CML patients treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: the stratification according to CCI pre-dasatinib therapy may allow to identify patients at risk to have major toxicities
CHARLSON COMORBIDITIES INDEX (CCI) MAY PREDICT COMPLIANCE AND DEVELOPMENT OF PLEURAL EFFUSIONS IN ELDERLY CHRONIC MYELOID LEUKEMIA (CML) RESISTANT/INTOLERANT PATIENTS TREATED WITH DASATINIB
CAVAZZINI, Francesco;
2010
Abstract
The Charlson comorbidities index (CCI) is a list of 19 conditions (including cardiologic, pulmonary diseases, diabetes, etc) with a weight assigned from 1 to 6, derived from relative risk estimates of a proportional hazard regression model using clinical data. Aims. We retrospectively evaluated the weight of CCI in a cohort of 125 elderly (> 60 years) chronic phase chronic myeloid leukemia (CP-CML) patients receiving dasatinib after imatinib resistance or intolerance. Methods. Score point 0 was assigned to 65 patients, whereas a score point >1 was assigned to 60 patients (35 patients =1, 19 patients= 2; 5 patients= 3; 1 patient= 4). Fifty-two patients received 70 mg twice daily and 56 patients received 100 mg once daily, in accordance with the results of the phase III trial, whereas 17 patients started with a dose less than 100 mg. Results. We found a significant association between CCI and drug reduction or suspension rate: during dasatinib treatment 49% of score 0 patients experienced a reduction of the dose compared to 63% of patients with score 1, 74% of patients with score 2 and 100% of patients with score 3 and 5 (P=0.03). Of the 65 patients with score 0, 29% had at least one suspension (79% for haematologic and 21% for non-hematologic toxicity, respectively), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-haematologic toxicity) and 100% of patients with score 3 and 4 (all patients for both types of toxicity) (P=0.003). Forty-one patients (32.8%) experienced pleural effusion during treatment: of these, 17 patients (26%) had score = 0, 13 patients (40%) score=1, 8 (42%) score=2 and 3 (60%) had score 3-4 (P=0.002). More pleural effusions occurred in patients who had score > 0 and who received higher dasatinib dose (140 mg). Nine patients experienced grade 3 and 31 patients grade 1-2 effusions: although the incidence of this event correlated with CCI stratification and dose received, its severity did not show the same correlation. Summary. In conclusion, in elderly CML patients treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: the stratification according to CCI pre-dasatinib therapy may allow to identify patients at risk to have major toxicitiesI documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
