BackgroundIbrutinib is an oral irreversible inhibitor of Bruton’s tyrosine kinase, indicated for the treatment of chronic lymphocytic leukaemia. The drug is generally well tolerated; however, not infrequent side effects are reported, with the major two being bleeding and ibrutinib-related atrial fibrillation. Atrial fibrillation pathogenesis in this setting is not completely clear, and no prospective studies have evaluated the impact of previous cardiologic history and baseline characteristics.MethodsWe prospectively performed cardiologic assessment in 43 CLL patients before starting ibrutinib therapy. Cardiologic workup included comorbidity collection and electrocardiographic and echocardiographic baseline evaluation.ResultsAfter a median observation of 8 months, seven patients developed atrial fibrillation (16.3%). Cases developing atrial fibrillation were all elderly males (p = 0.04), and mostly with a history of previous arterial hypertension (p = 0.009). Atrial fibrillation occurrence also correlated with the presence of one or more pre-existent cardiologic comorbidities (p = 0.03), with a higher atrial fibrillation risk score (calculated with comorbidities and cardiologic risk factor evaluation p < 0.001), and with higher left atrial diameter (p = 0.02) and area (p = 0.03) by echocardiography. The occurrence of atrial fibrillation was managed after an integrated cardio-oncologic evaluation: anticoagulation was started in 4 (57.1%) patients and beta-blockers or amiodarone in 5 (71.4%). One patient underwent electric cardioversion and another patient pacemaker positioning to normalise heart rate in order to continue ibrutinib.ConclusionOur data show that echocardiography is a highly informative and reproducible tool that should be included in pre-treatment workup for patients who are candidates for ibrutinib therapy.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0626-0) contains supplementary material, which is available to authorized users.

Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x10 9 /L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.

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