Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n= 95) or nilotinib (n= 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation

An outbreak of sepsis due to extensively drug- resistant originating from an environmental source in an Italian haematologic unit

Background: Multidrug-resistant (MDR) or extensively-drug-resistant (XDR) Pseudomonas aeruginosa (PSA) strains infections are a major concern in nosocomial environments being associated both with worse outcomes and with high mortality rates especially in oncologic and haematogic settings. In the Trieste University hospital, we experienced an outbreak of XDR-PSA bacteremia in the haematology unit probably caused by a reservoir in the toilets faucets. Materials/methods: The haematology unit in Trieste hospital has twelve double-bed rooms and a protected area with three single-bed rooms reserved to patients undergoing marrow transplants and severe neutropenia (neutrophils <0.5 x103/\u3bcL). From August until September 2017 we found 5 patients with sepsis or septic-shock due to an XDR-PSA. The bacterial identification was performed by Vitek-2 (bioM\ue9rieux). Minimal inhibitory concentrations (MICs) were determined by a micro-dilution method (Sensititre Diagnostic System, Trek), and interpreted according to the EUCAST criteria. MIC for ceftolozane/tazobactam was determined by e-test. Genotyping to determine genetic relatedness between isolates was performed by analysis of pulsed-field gel electrophoresis (PFGE) profiles of chromosomal DNA digested with SpeI. Results: All 5 consecutive strains of PSA from blood culture were resistant to piperacillin/tazobactam, ceftazidime, cefepime, ciprofloxacin, gentamicin, imipenem, meropenem and ceftolozane/tazobactam and susceptible to colistin and amikacin. None of these patients had any apparent source of bacteremia. Four out of five patients occupied the three isolation rooms. Two out of five patients had CVC-related sepsis and two died because of the XDR-PSA bacteremia (40% in-hospital mortality). No culture from rectal swabs and samples from ventilation filters was found positive for XDR-PSA which was instead found in the faucets of the toilets in the protected area. Pulse field analysis demonstrated that the strains both from blood cultures and from the toilets tabs were highly related suggesting that the outbreak was due to a single clone, probably originating from the tap water. The environmental disinfection of the ward succeeded in clearing the XDR-PSA strain and allowed to resume the regular transplant activity. Conclusions: The investigation of this dramatic outbreak of XDR PSA highlights the potential role of environmental sources acting as a reservoir of MDR/XDR nosocomial pathogens

Efficacy and toxicity of Decitabine in patients with acute myeloid leukemia (AML): A multicenter real-world experience

BACKGROUND: The hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice. PATIENTS AND METHODS: We retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial. Seventy-five (75%) pts received DAC as first line treatment (Cohort 1) and 29 pts as salvage therapy (Cohort 2). All pts received a DAC schedule of 20\u2009mg/sqm IV for 5-days, every 28 days. The median age was 72.5 years (74 in cohort 1 and 66 in cohort 2) and 16% of pts had an ECOG performance status >2 at the start of DAC treatment (with non-significant difference in the two cohorts). The cumulative illness rating scale (CIRS) was > 6 in 27% of pts. Forty-five pts (43%) had secondary AML. Bone marrow blast count was > 30% in 64% of patients (67/104). In the relapsed cohort 17/29 (59%) patients were treated with DAC after conventional CHT, 5/29 (17%) after allo-SCT and 7/29 (24%) after azacitidine therapy. RESULTS: A total of 469 DAC cycles were given to the 104 pts with a median of 3 cycles (range 1-21) and 45/104 (43%) pts received > 4 cycles. The Overall Response Rate (ORR\u2009=\u2009Complete Remission-CR plus Partial Remission-PR) was 33%, significantly higher in Cohort 1 (42%) compared to Cohort 2 (14%) (p\u2009=\u20090.009). The median duration of response was 6 months (range 1-20). In Cohort 1 the best response (CR or PR) was obtained between 3th and 6th cycle. In multivariate Cox regression analysis, achievement of CR or PR (HR\u2009=\u20090.78; p\u2009=\u20090.0004), CIRS\u2009<\u20096 (HR\u2009=\u20090.9; p\u2009=\u20090.04) and complex karyotype (HR\u2009=\u20090.8; p\u2009=\u20090.03) were significant predictors of better overall survival (OS). Median OS from the start of DAC therapy was 11 months for the whole population with a significant OS advantage in Cohort 1 (median OS 12.7 mths vs 6.3 mths; p\u2009=\u20090.003); median OS was significantly longer in responders compared to non-responders (22.6 mths vs 5.7 mths; p\u2009<\u20090.0001). At the last follow-up, 56 patients (54%) are still alive and 48 (46%) are dead (71% due to disease progression). The most common toxicities were myelosuppression and documented infectious complications that occurred mainly during the first 4 cycles. CONCLUSION: These data confirm the efficacy (ORR 33%) and the acceptable safety profile of DAC in the real life management of AML in elderly pts unsuitable for intensive CHT, with a significant better performance in first line therapy (ORR 42%, median OS 12.7 mths). The efficacy of DAC, both in first line and as salvage therapy, may probably be improved with combined treatment strategies and/or with different DAC schedules that could increase its anti-leukemic effect

Prospective validation of predictive value of abdominal computed tomography scan on time to first treatment in Rai 0 chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study

We performed an external and multicentric validation of the predictive value of abdominal computed tomography (aCT) on time to first treatment (TTFT) in early stage chronic lymphocytic leukemia (CLL) patients. METHODS: aCT was performed at diagnosis in 181 Rai 0 patients enrolled in the O-CLL1-GISL trial (clinicaltrial.gov ID:NCT00917549). RESULTS: Fifty-five patients showed an abnormal aCT. Patients with an abnormal aCT showed a significantly shorter TTFT than those with normal aCT (P < 0.0001). At multivariate analysis, aCT (P = 0.011), \u3b2-2 microglobulin (P = 0.019), and CD38 expression (P = 0.047) correlated with TTFT. Following IWCLL 2008 criteria, 112 (61.9%) cases remained at Rai 0, while 69 (38.1%) satisfied the criteria of clinical monoclonal B-cell lymphocytosis (cMBL). Reclassified Rai 0 patients with an abnormal aCT showed a significantly shorter TTFT than those with a normal aCT (P < 0.0001). At multivariate analysis, only aCT (P = 0.011) correlated with TTFT. Eleven cMBL cases (15.9%) showed an abnormal aCT and were reclassified as small lymphocytic lymphomas (SLL); nonetheless, TTFT was similar for cMBLs and SLLs. CONCLUSION: Our results confirm the ability of the abnormal aCT to predict progression in early stage cases