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The aim of this study was to evaluate the prognostic impact of FLT3-ITD in core-binding factor acute myeloid leukemia (CBFAML) in an international, multicenter survey of 97 patients of whom 52% had t(8;21)(q22;q22) and 48% had inv(16)(p13q22)/t(16;16)(p13;q22). The median age of the patients was 53 years (range, 19-81). Complete remission after anthracycline-based induction (n=86) and non-intensive therapy (n=11) was achieved in 97% and 36% of the patients, respectively. The median follow-up was 4.43 years (95% confidence interval [95% CI]: 3.35-7.39 years). The median survival after intensive and non-intensive treatment was not reached and 0.96 years, respectively. Among intensively treated patients, inv(16) with trisomy 22 (n=11) was associated with a favorable 4-year relapse-free survival rate of 80% (95% CI: 59-100%) as compared to 38% (95% CI: 27-54%; P=0.02) in all other patients with CBFAML/ FLT3-ITD (n=75). Overall, 24 patients underwent allogeneic hematopoietic cell transplantation (HCT), 12 in first complete remission and 12 after relapse. Allogeneic HCT in first complete remission was not beneficial (P=0.60); however, allogeneic HCT seemed to improve median survival in relapsed patients compared to that of patients treated with chemotherapy (not reached vs. 0.6 years, respectively; P=0.002). Excluding patients with inv(16) with trisomy 22, our data indicate that compathe outcome of CBF-AML patients with FLT3-ITD may be inferior to that of patients without FLT3-ITD (based on previously published data), suggesting that prognostically CBF-AML patients with FLT3-ITD should not be classified as favorable-risk. FLT3-inhibitors may improve the outcome of these patients.

Background: Up to now there have been missing data in the literature concerning relationship of galactomannan (GM) detected in bronchoalveolar lavage (BAL) fluid and type of abnormality on pulmonary high resolution computer tomography (HRCT) in patients (pts.) with pulmonary invasive aspergillosis (IPA). Aims: To evaluate relationship between sensitivity of GM detected in BAL fluid and serum (S-GM) and type of abnormality on pulmonary HRCT in pts. with IPA. Methods: We retrospectively analyzed mentioned relationship in pts. with IPA entered in „Fungal InfectioN Database (FIND)“ aspergillus between 2001 and 2012.

Dasatinib is effective second line treatment for patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. We report here the first experiences with dasatinib therapy in 71 CML patients resistant or intolerant to imatinib from the real clinical practice of 6 hematological centers in the Czech Republic. Dose 100 mg daily and 70 mg twice daily was administered to patients with chronic phase (CP) and advanced phases (AP) CML. In chronic phase (n=46), complete hematological reponse (CHR) was achieved in 97%, major cytogenetic reponse (MCgR) in 77% and complete cytogenetic response (CCgR) in 67%. Major molecular reponse (MMR) was achieved in 19/31 patients in median of 10 months. In advanced phase (n=25), CHR was attained in 77%, MCgR in 39%, CCgR in 33% and MMR in 2/18 patients. Eleven different baseline mutations were followed up in 15 patients. Dasatinib eliminated mutations in most of the patients, but 3 patients acquired a new one. Novel mutations were detected under dasatinib therapy in 2 patients. Dasatinib was well tolerated, cytopenias were common and was managed by dose modification. The estimated progression free survival (PFS) at 12 months was 97+/-3% in CP and 62+/-21% in AP. The median time to treatment failure was 605 days in AP while it was not reached in CP patients. Our clinical experiences, described here, confirmed that dasatinib is associated with high response rates especially in imatinib resistant or intolerant CML patients in chronic phase.

Clinical studies have suggested that rates of infusion-related reactions (IRRs) may be higher with amphotericin B colloidal dispersion (ABCD) versus other forms of amphotericin B. However, these studies did not permit the use of pre-medications upfront, which are now commonly used. Objectives were to describe the use of pre-medications and determine the rate of IRRs in the real-world setting. PRoACT, a multicentre, worldwide observational registry, captured real-world data about pre-medication practices and IRRs in patients receiving ABCD. Eligible patients were those beginning treatment with ABCD ; treatment was according to the site's standard treatment practice. Incidence of IRRs was collected during the first 10 days of ABCD therapy. Clinical response data were collected 12 weeks after treatment start. One hundred and seventy patients from 21 worldwide sites were included (median age 37 years ; 52% male). There were a total of 1230 ABCD infusions (mean dose 2.8 mg/kg/day) ; 90% of the infusions (1105/1230) had pre-medication. Common pre-medications included corticosteroids, antihistamines, paracetamol (acetaminophen) and metamizole. The overall IRR rate was 12% (147/1230) and was lower in infusions with pre-medication (11%) versus no pre-medication (22%), P < 0.001. Corticosteroids were associated with a decreased incidence of IRRs (P < 0.05), while paracetamol and antihistamines were not. The most common IRRs were chills (7%), fever (7%) and rigors (5%). Clearance of the fungal infection occurred in 52% of the participants. These data suggest a lower rate of IRRs with ABCD than previously reported. Pre-medication is associated with decreased IRR incidence. Corticosteroids in particular appear to decrease IRRs while paracetamol and antihistamines, though commonly used, do not.

Objectives: “Fungal InfectioN Database” (FIND) represents international database of invasive fungal infections in Czech and Slovak hematooncological departments. FIND - aspergillus covers all case of invasive aspergillosis (IA) in participating centers since 2001. Methods: The goal of our retrospective analysis was to evaluate incidence, early diagnostic procedures and effect of antifungal therapy in proven and probable IA that occurred in 16 institutions participating in FIND database between 2001–2011. Till 2009 we followed EORTC/MSG 2002 and from 2010 EORTC/MSG 2008 criteria in evaluation of IA diagnosis and therapy response. Results: 256 probable and 58 proven IA (91% isolated pulmonary IA, IPA) have been documented. Prolonged and profound neutropenia (61%) and long-term use of corticosteroids (28%) were identified as the major risk factors of IA. 68% pts. had consecutive positivity of serum-galactomannan (S-GM) (OD index >0.5). 83% pts. with IPA and bronchoalveolar lavage (BAL) had positive GM in BAL fluid (OD index >0.5). In pts. with IPA only 7.6% BAL fluids and 8.4% sputum samples had positive microscopic result for filamentous fungi and 2.2% BAL fluids and 1.8% sputum samples had positive culture for Aspergillus spp. The primary antifungal therapy of IA was used in 89% pts. - 41% voriconazole (VORI), 7% echinocandins (ECHINO), 23% VORI+ECHINO, 7% amphotericine B deoxycholate (C-AMB) and 9% lipid- based AMB (LBA). Overall RR to primary therapy of IA was 46% - VORI 55%, VORI+ECHINO 54%, C-AMB 35%, LBA 39%, ECHINO 25%. There was a statistically significant difference in overall RR to targeted therapy in pts. with neutrophil count 1.0x10e9/L at the end of therapy (21% vs. 71%). The overall mortality rate was 61%, with 39% attributable to IA. Conclusion: On the basis of our analysis we confirm typical risk factors for IA and critical role of S-GM and CT for early diagnosis and prompt start of antifungal therapy of IA. A reasonable treatment response was achieved using VORI, VORI+ECHINO or LBA in primary therapy of IA. We have confirmed neutropenia at the end of antifungal therapy as the major predictive factor for therapeutic response. On behalf of CELL - The Czech leukemia study group for life.

Invasive aspergillosis in patients with hematological malignancies in Czech, Slovak and Croatian hematooncological departments: Fungal INfection Database (FIND) analysis (2001-2014) - an update