CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program

Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT

Disturbo Pervasivo dello Sviluppo - Non altrimenti Specificato: Percorsi Possibili e Prospettive per il Futuro

I Disturbi Pervasivi dello Sviluppo di tipo Non Altrimenti Specificato (DPS-NAS) rappresentano una categoria diagnostica in cui i sintomi, costituiti da deficit nell’area dell’interazione sociale e da disturbi nell’area della comunicazione e degli interessi, non raggiungono, per gravità o quantità, quelli che sono i criteri stabiliti per la diagnosi di autismo o di altri DPS. I sintomi presentati da questi pazienti sono definiti “sottosoglia”: possono essere non sufficienti sia dal punto di vista qualitativo (la sintomatologia appare più lieve), che dal punto di vista quantitativo (non si raggiunge un numero adeguato di sintomi per fare diagnosi di autismo o di altro DPS). Data l’aspecificità del quadro sintomatologico e quindi la mancanza di precisi criteri diagnostici, lo scopo del presente lavoro è quello di scattare un’istantanea delle caratteristiche cliniche di un campione di bambini con diagnosi di DPS-NAS. Dall’analisi dei risultati è emerso come sia chiara la difficoltà di categorizzare rigidamente un disturbo dai confini non ben distinti, eterogeneo nelle sue manifestazioni cliniche ma che al tempo stesso sembra mostrare, al suo interno, la presenza di caratteristiche comuni ben delineate, quali l'insorgenza precoce dei sintomi e la presenza di deficit nell’interazione sociale. Con la nuova classificazione prevista nel DSM-5 e la comparsa della nuova categoria diagnostica denominata “Social Communication Disorder”, si tracceranno nuovi confini nosografici, con il tentativo di fornire punti di riferimento più stabili e chiari per la progettazione di interventi terapeutici mirati

Advanced non-small cell lung cancer: Rapid evaluation of EGFR status on fine-needle cytology samples using Idylla

Advanced non-small cell lung cancer (NSCLC) needs to be managed rapidly; therefore, a rapid assessment of the epidermal growth factor receptor (EGFR) status is mandatory. Computed Tomography (CT)-guided or Ultrasound (US)-guided Fine-Needle Aspiration Cytology (FNAC) allows a rapid diagnosis of both primary and metastatic tumor through rapid on-site evaluation (ROSE) and the proper management of diagnostic material. Idylla (Biocartis, Mechelen, Belgium) is an automated RT-PCR system which evaluates the mutational status of specific genes in less than two hours. In this study, the EGFR mutational status in advanced NSCLC was analyzed on 28 FNAC samples with Idylla. After ROSE, residual FNAC material and/or additional passes were pipetted into the Idylla EGFR cartridge. Patients endorsed a consent form before carrying out the analysis. Results were controlled by pyrosequencing. Adequate EGFR status was obtained in 26/28 cases (22 wild type and 4 mutated). Mutated cases harbored EGFR Exon 19 deletion and L858R point mutation. In 2/28 cases the analysis failed. The combination of FNAC, ROSE and Idylla is a rapid, accurate and effective method that can be conveniently used to assess EGFR status in advanced NSCLC

In vivo T-cell depletion with pretransplant low-dose antithymocyte globulin is associated with reduced transplant-related mortality and improved clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation from unrelated and partially matched related donors

Graft versus host disease (GVHD) represents one of the major limiting factors to the successful applicability of hematopoietic stem cells transplantation (HSCT). In particular, allogeneic HSCT from alternative donors with unmanipulated graft results in an increased risk of both acute and chronic GVHD compared with matched sibling donor transplants [1]. At the present, none of the GVHD prophylactic strategies currently in use, including calcineurin inhibitors [2], T-lymphocyte depletion, and monoclonal antibodies [3,4], have been proven to be of superior efficacy over another

Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation: Quantification of Iron Burden by a Superconducting Quantum Interference Device (SQUID) and Therapeutic Effectiveness of Phlebotomy

Iron overload (IO) is a known adverse prognostic factor in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia and appears to play a similar role in patients with other hematologic disorders. The estimation of IO is based primarily on serum ferritin level; however, many confounding factors can result in ferritin overestimation, especially in HSCT recipients. The aim of the present study was to quantify IO after HSCT using a superconducting quantum interference device (SQUID), and to evaluate the impact of IO on hepatic function and infections. In addition, the feasibility of iron depletion was investigated. A total of 102 consecutive allogeneic HSCT recipients admitted to our outpatient department between December 2005, and December 2007, were analyzed. Primary diagnosis included acute leukemia/myelodysplastic syndrome in 61% of cases. Assessment of IO after HSCT included serum ferritin; in those with hyperferritinemia (ferritin > 1000 ng/mL), liver iron concentration (LIC) was evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to patients with moderate IO (LIC 1000-2000 μg Fe/g wet weight [ww]) or severe IO (LIC >2000 μg Fe/g ww). Fifty-seven patients had a ferritin level <1000 ng/mL: the median time between HSCT and assessment of ferritin level was 1006 days (range, 93-5239 days), significantly different from the median time of 183 days (range, 78-2957 days) in the 45 patients with a ferritin level >1000 ng/mL. Out of 42 patients evaluated by SQUID, 29 had moderate to severe IO (median LIC value, 1493 μg Fe/g ww [range, 1030-3253]). In a multivariate analysis, a significant correlation was found between a ferritin level >1000 ng/mL and the presence of at least one abnormal liver function test (LFT) ORo = 6.8; 95% CI = 2.2-20.6). In addition, the rate of proven/probable invasive fungal disease was significantly higher in the patients with hyperferritinemia (13% vs 0%; P = .006). Nineteen of the 24 patients considered eligible for iron-depletion therapy underwent regular phlebotomy; 13 completed the program in a median of 287 days (range, 92-779 days), reaching the target of a ferritin level < 500 ng/mL; LIC was significantly reduced (median, 1419 μg Fe/g ww to 625 μg Fe/g ww; P < .001) in 8 of the 9 patients who were revaluated by SQUID at the end of the iron-depletion program. In conclusion, the measurement of LIC obtained by SQUID documented the presence of moderate/severe IO in 69% of the patients with a high ferritin level. Our data showed that in HSCT recipients, high ferritin level is an independent risk factor for abnormal LFTs, and IO may be considered a potential risk factor for fungal infections. A phlebotomy program may be feasible in two-thirds of the patients who might benefit from iron depletion. © 2010 American Society for Blood and Marrow Transplantation

Blood stream infections after allogeneic stem cell transplantation: a single-center experience with the use of levofloxacin prophylaxis

Blood stream infections (BSIs) remain one of the major causes of morbidity and mortality for patients receiving an allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the incidence and characteristics of BSI within 1 year after allogeneic HSCT in 269 consecutive adult patients who received antibacterial prophylaxis with levofloxacin. Cumulative incidence of BSI was 12% (95% confidence interval, 8-16%). Bacteria were responsible for 30 out of the 32 BSI, while fungi were responsible for 2 episodes of BSI. The median onset of BSI was day 8 (range 1-328 days) post transplant, and 66% of BSI occurred before neutrophil recovery. Gram-positive organisms accounted for 60% (n=18) of bacteremia, and gram-negative isolates for 40% (n=12) of the cases. Coagulase-negative staphylococci were the most commonly isolated gram-positive pathogens (53% of the cases), while Escherichia coli was the most commonly isolated gram-negative bacteria (58% of the cases). Candida albicans and Candida guillermondii were isolated from patients with candidemia. Resistance to fluoroquinolones (FQ) was common with 13% of gram-positive isolates being susceptible to FQ, while 50% of the gram-negative rods were susceptible to FQ. Crude mortality and mortality attributable to BSI were both 3% (1 of 32). In conclusion, our data suggest that despite the emergence of antibiotic resistance, FQ prophylaxis may be considered an appealing approach in allogeneic HSCT recipients and is also worth evaluating in randomized studies