Isabella Capodanno

Incidence, risk factors and management of pleural effusions during dasatinib treatment in unselected elderly patients with chronic myelogenous leukaemia

To assess the most important features and clinical impact of pleural effusions, which are a common toxicity during dasatinib treatment and often impair its high efficacy, 172 unselected consecutive patients with chronic myelogenous leukaemia in chronic phase treated in 27 Italian centres, with dasatinib when aged >60 years for resistance/intolerance to imatinib, were examined. During treatment, 52/172 patients (30.2%) presented pleural effusion, which was grades 1–2 in 38 patients and grades 3–4 in 14 patients (8.1% of the entire cohort of patients), according to the WHO scale; in 14/52 patients (26.9%), there was a concomitant pericardial effusion. Pleural effusion was recurrent in 25/52 patients (48.0%). Median time from dasatinib to first pleural effusion was 11.0 months (interquartile range 3.6–18.6). Eleven patients (6.4%) required permanent dasatinib discontinuation. Only presence of concomitant pulmonary disease ( p = 0.035) and initial daily dose of dasatinib (140 mg vs 100 mg, p = 0.014) were significantly associated with pleural effusions. There were no differences among patients with or without pleural effusions as concerns response rates and overall survival. Pleural effusions were common in our unselected ‘real‐life’ population of elderly patients but were clinically manageable and did not seem to affect treatment results. Copyright

Outcome of frail elderly patients with diffuse large B-cell lymphoma prospectively identified by Comprehensive Geriatric Assessment: results from a study of the Fondazione Italiana Linfomi

Abstract In 2003 the Fondazione Italiana Linfomi (FIL) started a clinical research program for investigating initial treatment of frail elderly patients with diffuse large B-cell lymphoma (DLBCL) identified by Comprehensive Geriatric Assessment (CGA). From 2003 to 2006, 334 elderly patients underwent CGA assessment, and 99 patients were classified as frail. Frail patients had a median age of 78 years, stage III–IV disease in 62% and age-adjusted International Prognostic Index (aaIPI) of 2–3 in 53%. Treatment consisted of several different regimens according to physician discretion. After a median follow-up of 36 months, 5-year overall survival (OS) was 28%. In multivariate analysis, aaIPI 2–3 (p = 0.005) and the presence of respiratory comorbidity (p = 0.044) were the only factors that showed independent correlation with OS. Frail patients had a poorer outcome compared with fit patients also if they were treated with rituximab-containing combination chemotherapy (hazard ratio 2.37, 95% confidence interval 1.48–3.78; p < 0.001). CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL.

Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation Arising in a Renal Pseudocyst

Primary renal lymphomas are very rare, and primary kidney-limited lymphomas with cystic presentation have never been described before. This study reports a case of diffuse large B-cell lymphoma associated with chronic inflammation occurring in a renal pseudocyst: an infrequent neoplasm with an unusual and subtle clinical presentation.

A population‐based study of chronic myeloid leukemia patients treated with imatinib in first line

Chronic myeloid leukemia (CML) treatment is based on company‐sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first‐line therapy. These studies included patients selected according to many inclusion–exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real‐life), inclusion–exclusion criteria do not exist, and the treatment outcome does not only depend on the choice of first‐line TKI but also on second‐ and third‐line TKIs. To investigate in a real‐life setting the response and the outcome on first‐line imatinib, with switch to second generation TKIs in case of unsatisfying response or intolerance, we analyzed all newly diagnosed patients (N = 236), living in two Italian regions, registered in a prospective study according to population‐based criteria and treated front‐line with imatinib. A switch from imatinib to second‐generation TKIs was reported in 14% of patients for side effects and in 24% for failure or suboptimal response, with an improvement of molecular response in 57% of them. The 5‐year overall survival (OS) and leukemia‐related survival (LRS) were 85% and 93%, respectively; the 4‐year rates of MR3.0 and MR4.0 were 75% and 48%, respectively. Cardiovascular complications were reported in 4% of patients treated with imatinib alone and in 6% of patients receiving nilotinib as second‐line. Older age (≥70 years) affected OS, but not LRS. These data provide an unbiased reference on the CML management and on the results of TKI treatment in real‐life, according to ELN recommendations, using imatinib as first‐line treatment and second‐generation TKIs as second‐line therapy. Am. J. Hematol. 92:82–87, 2017.

Frontline Dasatinib Treatment in a “Real-Life” Cohort of Patients Older than 65 Years with Chronic Myeloid Leukemia

Dasatinib (DAS) has been licensed for the frontline treatment in chronic myeloid leukemia (CML). However, very few data are available regarding its efficacy and toxicity in elderly patients with CML outside clinical trials. To address this issue, we set out a “real-life” cohort of 65 chronic phase CML patients older than 65 years (median age 75.1 years) treated frontline with DAS in 26 Italian centers from June 2012 to June 2015, focusing our attention on toxicity and efficacy data. One third of patients (20/65: 30.7%) had 3 or more comorbidities and required concomitant therapies; according to Sokal classification, 3 patients (4.6%) were low risk, 39 (60.0%) intermediate risk, and 20 (30.8%) high risk, whereas 3 (4.6%) were not classifiable. DAS starting dose was 100 mg once a day in 54 patients (83.0%), whereas 11 patients (17.0%) received less than 100 mg/day. Grade 3/4 hematologic and extrahematologic toxicities were reported in 8 (12.3%) and 12 (18.5%) patients, respectively. Overall, 10 patients (15.4%) permanently discontinued DAS because of toxicities. Pleural effusions (all WHO grades) occurred in 12 patients (18.5%) and in 5 of them occurred during the first 3 months. DAS treatment induced in 60/65 patients (92.3%) a complete cytogenetic response and in 50/65 (76.9%) also a major molecular response. These findings show that DAS might play an important role in the frontline treatment of CML patients >65 years old, proving efficacy and having a favorable safety profile also in elderly subjects with comorbidities.

Chronic myeloid leukaemia with extreme thrombocytosis at presentation: incidence, clinical findings and outcome

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Anaplastic Lymphoma Kinase–Positive Large B-Cell Lymphoma Description of a Case With an Unexpected Clinical Outcome

Anaplastic lymphoma kinase–positive (ALK-positive) large B-cell lymphoma is a rare and aggressive variant of large B-cell lymphoma (LBCL), first reported by Delsol et al in 1997, showing distinctive morphologic, immunophenotypic and cytogenetic features. The latest 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid tissues recognizes ALK-positive LBCL as a separate entity. Here, we report a case of ALK-positive large B-cell lymphoma in a 53-year-old man with diffuse abdominal and mediastinal lymph-nodes involvement. According to the Ann Arbor staging system, the patient had a stage IIIB lymphoma. The age-adjusted International Prognostic Index was 2 (stage III and elevated lactate dehydrogenase), so the disease was considered high risk. The patient underwent chemotherapy, radiotherapy, and an autologous stem cell transplantation. The patient is alive and free of disease 35 months after diagnosis.