ALBERT

Description: The therapeutic approach for acute myeloid leukemia (AML) in elderly patients is generally tailored on the basis of age, performance status, comorbidities and patient consent. Toxicity and low-response rates are major constraints and, in general, the therapeutic options are finally conditioned by the clinicians’ views about the patients’ health status and preferences. In this setting, the patients’ perception of their own health (health-related quality of life, or HRQOL) may be useful. With this purpose, we designed a prospective multicenter study to evaluate the predictive potentials of HRQOL measures on prognosis and outcome in elderly AML patients (aged over 60 years). We here present pilot baseline results on data obtained from 25 AML patients of median age 74 (range 60–91) yrs. HRQOL measures were obtained by applying the QOL-E©questionnaire at diagnosis. Reliability of the questionnaire was evaluated and associations with patient and disease-related factors were investigated. We found that the QOL-E© questionnaire as highly reliable in the AML patients (standardized Cronbach alpha coefficients〉 0.70). Table 1. Reliability of the QOL-E questionnaire. QOL-E© domains Standardized Cronbach alpha coefficients QOL-E©scores were particularly low (reflecting poor HRQOL) in the fatigue and disease-specific domains. Physical 0.90 Functional 0.80 Social 0.80 Sexual 0.81 Fatigue 0.77 Disease-Specific 0.78 Total 0.70 Table 2. QOL-E scores in the AML patients. QOL-E© domains QOL-E© scores* *Scores are standardized, expressed in percentage ±SEM Physical 60 ± 6 Functional 64 ± 4 Social 56 ± 6 Sexual 50 ± 8 Fatigue 34 ± 4 Disease-specific 26 ± 4 Total 38 ± 5 In this study, male AML patients (15 patients) perceived better well-being in the QOL-E© disease-specific domain than females (33±4 versus 15±7 %, p=0.04). The lack of domestic assistance (reflecting no previous need for help at home) was associated with better functional scores (p=0.037) and a lesser sense of fatigue (p=0.042) at diagnosis. Patients with concomitant diseases had a poorer sense of physical wellbeing (45± %) versus those without (28±8%, p=0.01). Increasing age significantly correlated with decreasing QOL-E© physical (r=−0.414, p=0.04), functional (r=−0.470, p=0.018) and fatigue (r=−0.487, p=0.015) scores. ECOG performance status (objective score of patient’s wellbeing) was not associated with subjective measures of HRQOL in the single domains, but only with the total score (r=−0.570, p=0.04). Noteworthy, the QOL-E© disease-specific scores correlated with the percentage of peripheral blasts (r=−0.302, p=0.078) and bone marrow blasts (r=−0.387, p=0.024). In conclusion, QOL-E© is a very simple and reliable instrument for the assessment of HRQOL in elderly patients with AML. At diagnosis HRQOL is poor, especially with increasing age and in patients with a high blast count. Future prospective results in an adequate number of patients may provide useful information on the implementation of patient-tailored therapy in this particular category of AML patients.

Description: The increase of median survival of the general population results in a higher incidence of Chronic Myeloid Leukemia (CML) in the elderly. In our series of 260 cases from a single institution the mean age of CML cases was 52.5 from 1977 to 1987 and 61.9 from 1999 to 2003; in other words, in the last 5 years 39.6% of our CML cases was over 70 years of age. The introduction of Imatinib (STI) has changed the treatment strategy in CML elderly patients, previously treated with hydroxyurea (HU). Efficacy, tolerability and cost of STI therapy in this CML setting are worth to be considered. For this purpose we retrospectively evaluated our elderly CML patients treated with STI. Our series consists in 24 cases, M/F 18/6, with a median age at diagnosis of 70.1 yrs (60–83), and 73.4 (65–83) at time of STI therapy; Co-morbidity included hypertension (5 cases), renal failure (2), cardiovascular diseases (4), diabetis (1), psoriasis (1), B-cell chronic lymphocytic leukaemia (B-CLL) (1). The mean interval from diagnosis to STI was 2.6 yrs (0-7). Sokal index was low in 4 cases, intermediate in 18, high in 2; Euro index was low in 15, intermediate in 7, high in 2. All cases were bcr/abl positive (p210), 19 Ph1+, 4 Ph1-. Four patients, one in AP, were untreated. Six cases had received HU, 3 in accelerate phase (AP). Out of 14 cases previously treated with interferon (IFN) for 1 to 43 months, 5 patients were intolerant, 7 resistant (1 in AP), while 2 patients obtained haematological and cytogenetic complete response and received IFN treatment for 24 and 29 months, respectively. STI was administered at 400 mg/day in CP and 600 mg/day in AP, for a mean period of 2 yrs (1 to 46 months). All cases but 3, 2 in AP and 1 in chronic phase (CP), either obtained or maintained the hematological response. After 6 to 12 months of STI therapy, out of 24 cases, 11 obtained complete cytogenetic (CG) response (1 case in AP), 1 minor, 3 no CG response; in the remaining cases CG response was not evaluable, in 2 cases because CG response was already obtained after IFN therapy, in 3 because of short period of therapy, and in 4 because Ph1 negative at onset. Quantitative molecular response, evaluated in 9 out of 11 patients achieving CG response, was obtained in 8 cases; notably, in 4 cases bcr/abl was so low to become undetectable. Tolerability was generally good in all but 2 cases, requiring STI permanent withdrawal; one patient presented subdural hemorrage needing surgery, the other one presented hepatic failure The remaining toxicity consisted of grade 3 cough, scrotal oedema, reversible lethargy because of cerebral oedema; and fatigue requiring temporary withdrawal or dose reduction in 7 patients. Also hematological toxicity required temporary drug withdrawal 2 cases. Out of 4 patients requiring permanent dose reduction to 300 mg/day, 3 are maintaining CG and molecular response, while one patients lost CG response. In detail, out of 5 cases in AP, 3 died of progressive disease, one maintains haematological and the last CG complete response. Interestingly the patients affected by psoriasis demonstrated a clear improvement of skin lesions and the patient with concomitant B-CLL achieved a response at phenotypic level. At the time of the present report 3 patients died, all in AP because of disease progression. According to the present data STI therapy is indicated in CML elderly patients.

Description: Recombinant human epoetin (rHu-EPO) is an effective treatment of anemia in myelodysplastic syndrome (MDS) in up to 40% of patients, mainly in low-risk MDS not yet requiring transfusions. Darbepoetin alpha is an rHuEPO analogue with an approximately 3-fold longer half-life than epoetin alfa, which leads to greater biological activity. We evaluated its effects on anemia in a pilot group of low and intermediate-1 risk MDS patients. The primary objective was to evaluate the efficacy of darbepoetin in terms of response/no response. Secondary objectives were to evaluate: 1) drug safety; 2) variations of Hb and the number of monthly transfusions; 3) changes in quality of life (QoL) of patients; and 4) changes in apoptosis of CD34+ cells. Twelve patients with Hb