BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) spread and infections in patients with haematological malignancies are a serious concern especially in endemic areas. Treatment failures and delay in appropriate therapy for CRKP infections are frequent and the mortality rate associated with CRKP bacteremia in neutropenic haematological patients is reported about 60%.MethodsHaematological patients harboring CRKP hospitalized between February 2012 and May 2013 in an Italian Teaching hospital were examined. Conditions favouring CRKP spread in a haematological unit, risk factors for bacteremia in CRKP-carriers and for CRKP bacteremia-related death were evaluated in this observational retrospective study.ResultsCRKP was isolated in 22 patients, 14 (64%) had bacteremia. Control measures implementation, particularly the weekly rectal screening for CRKP performed in all hospitalized patients and contact precautions for CRKP-carriers and newly admitted patients until proved CRKP-negative, reduced significantly the CRKP spread (14 new carriers identified of 131 screened patients vs 5 of 242 after the intervention, p = 0.001). Fifty-eight percent of carriers developed CRKP bacteremia, and acute myeloid leukemia (AML) resulted independently associated with the bacteremia occurrence (p = 0.02). CRKP bacteremias developed mainly during neutropenia (86%) and in CRKP-carriers (79%). CRKP bacteremias were breakthrough in 10 cases (71%). Ten of 14 patient with CRKP bacteremias died (71%) and all had AML. The 70% of fatal bacteremias occurred in patients not yet recognized as CRKP-carriers and 80% were breakthrough. Initial adequate antibiotic therapy resulted the only independent factor able to protect against death (p = 0.02).ConclusionsThe identification of CRKP-carriers is confirmed critical to prevent CRKP spread. AML patients colonized by CRKP resulted at high risk of CRKP-bacteremia and poor outcome and the adequacy of the initial antibiotic therapy may be effective to improve survival. To limit the increase of resistance, the extensive use of antibiotics active against CRKP should be avoided, but in the setting of high CRKP pressure and high-risk CRKP-colonized haematological patients, timely empiric antibiotic combinations active against CRKP could be suggested as treatment of febrile neutropenia.

A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.

To shed light into the molecular basis of Ph+ acute lymphoblastic leukemia and to investigate the prognostic role of additional genomic lesions, we analyzed copy number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult Ph+ acute lymphoblastic leukemia patients enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy. This analysis showed that Ph+ acute lymphoblastic leukemia patients carry 7.8 lesions/case on average, with deletions outnumbering gains (88% vs 12%). The most common deletions were those targeting IKZF1, PAX5 and CDKN2A/B detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of IKZF1 plus CDKN2A/B and/or PAX5 had a significantly worse disease-free survival (24.9% vs 43.3%, p=0.026). The only IKZF1 isoform impacting on prognosis was the dominant negative (p=0.003). Copy number aberrations analysis showed that 18% of patients harbored MEF2C deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular remission (p=0.05) and had a favorable impact on disease-free survival (64.3% vs 32.1% at 36 months, p=0.031). These findings retain statistical significance also in multivariate analysis (p=0.057). KRAS deletions, detected in 6% of cases, were associated with the achievement of a complete molecular remission (p=0.009). These results indicate that in adult Ph+ acute lymphoblastic leukemia a detailed evaluation of additional deletions - including CDKN2A/B, PAX5, IKZF1, MEF2C and KRAS - has prognostic implications and should be incorporated in the design of always more personalized treatment strategies.

PICCs represent a useful and safe alternative to conventional CVAD for the management of patients with hematologic malignancies.

The online version of this article has a Supplementary Appendix. BackgroundPosaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia. Design and MethodsThe impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs. ResultsProven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs. ConclusionsPrimary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a "real-life" scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous.

We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/ normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI > 25). An increased BMI was associated with older age (P < .0001) and male sex (P ‫؍‬ .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio ‫؍‬ 7.24; 95% CI, 1.50-34; P ‫؍‬ .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P ‫؍‬ .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio ‫؍‬ 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P ‫؍‬ .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols. (Blood. 2012;119(1):49-54) IntroductionObesity has received considerable attention in the medical community because of its negative impact on human health. More recently, excess of body weight has been associated with an increased risk of a wide range of malignancies. [1][2][3] In a meta-analysis of cohort studies, Larsson and Wolk reported epidemiologic evidence suggesting that an excess of body weight is a risk factor for several hematologic cancers, including leukemia, non-Hodgkin lymphoma, and multiple myeloma. 4 In particular, compared with nonoverweight persons, the relative risk of leukemia for overweight and obese persons was reported to be 1.14 and 1.39, respectively, whereas a 5-kg/m 2 increase in body mass index (BMI) was associated with a 13% increased risk of leukemia. 4 As to the impact of BMI on treatment response and outcome, a number of studies have shown that obesity is associated with a poorer overall survival and disease-free survival in patients with breast cancer. 5,6 By contrast, the correlation between BMI and treatment outcome has not yet been investigated in patients with leukemia.Acute promyelocytic leukemia (APL), once known as the most rapidly fatal leukemia subtype, is nowadays considered the most frequently curable acute leukemia of adults. 7 Indeed, modern combined approaches with all-trans retinoic acid and anthracycline chemotherapy yield complete remission rates greater than 90% and long-term cure rates of 70% to 75%. [8][9][10][11] Disease relapse and death during induction because of hemorrhage, infection, or differentiation syndro...

The authors could also show an increased pCrKL/CrKL ratio as a surrogate marker for the bcr-abl tyrosine kinase (TK) activity in patients exhibiting the e13a2 transcript type. It is tempting to speculate that patients with higher TK-activity should also be treated by either higher doses of imatinib or more potent second generation TKinhibitors. Whether this approach would also augment recently reported side effects of imatinib on bone metabolism is of special concern in a pediatric cohort which is still in a period of growth.7, 8 We, therefore, fully agree with the suggestion by Lucas et al. that the analysis of the transcript type in patients with CML should be included in the analysis of response data from trials with TK inhibitors. Children's Hospital, University Hospital Carl Gustav Carus, Technical University Dresden, Germany Fetscherstr. 74, D-01307 Dresden, Germany. Phone: international +49.0.351.4583522. Fax: international +49 (0) Haematologica. 2010;95:852-853. doi:10.3324/haematol.2009 Early hemorrhagic death before starting therapy in acute promyelocytic leukemia: association with high white blood cell count, late diagnosis and delayed treatment initiationEarly death is one of the major causes of failure in acute promyelocytic leukemia (APL), it occurs in approximately 5-10% of newly diagnosed cases and is most frequently due to severe intracranial or pulmonary bleeding. In the present single center study, we reviewed the clinical and biological features of patients who developed severe hemorrhagic complications before starting all-trans retinoic acid and chemotherapy, and found that late diagnosis and delayed treatment initiation, in conjunction with elevated WBC counts, are significantly associated with severe bleeding and early death.Severe bleeding is a well known major complication of APL which leads to early death in approximately 5-10% of patients diagnosed in developed countries and in 20-30% of patients living in less privileged regions. Hemorrhages are commonly attributed in this leukemia to the frequent diffuse activation of coagulation, hyperfibrinolysis, and non-specific proteolytic activity, 1-4 and have also been reported to occur before the diagnosis of APL has been made and therapy started.3 Systematic data on patients developing this severe complication before treatment are extremely scarce in the literature and these cases are usuhaematologica | 2010; 95 (5) 853Letters to the Editor © F e r r a t a S t o r t i F o u n d a t i o n ally omitted from large clinical trial reports. We reviewed our database of 105 consecutive patients with newly diagnosed APL observed at a single institution from March 1993 to October 2008. Diagnosis was initially established morphologically and subsequently confirmed in all cases by RT-PCR identification of the specific PML/RARA fusion gene. In all cases, records were available for complete blood counts, peripheral and bone marrow blast count, PML/RARA fusion gene type, coagulation laboratory parameters, time interval between diagnosis and hosp...

Background. KPC-K.pneumoniae bloodstream infection (KPC-KpBSI) mortality rate in patients with hematological malignancies is reported about 60%. The initial treatment active against KPC-K.pneumoniae is crucial for survival and KPC-K.pneumoniae rectal colonization usually precedes KPC-KpBSI. We evaluated the impact on KPC-KpBSI mortality of the preemptive use of antibiotics active against KPC-K.pneumoniae, as opposed to inactive or standard empiric antibiotics, for the empiric treatment of febrile neutropenia episodes in patients with hematological malignancy identified as KPC-K.pneumoniae intestinal carriers. Methods. We compared the outcomes of KPC-KpBSIs occurring in high-risk patients with hematological malignancy known to be colonized with KPC-K.pneumoniae, during two time periods: March 2012-December 2013 (Period 1, initial approach to KPC-K.pneumoniae spread) and January 2017-October 2018 (Period 2, full application of the preemptive strategy). The relative importance of the various prognostic factors that could influence death rates were assessed by forward stepwise logistic regression models.Results. KPC-KpBSI-related mortality in patients with hematological malignancies identified as KPC-K.pneumoniae carriers dropped from 50% in Period 1 to 6% in Period 2 (p<0.01), from 58% to 9% in acute myeloid leukemia carriers (p<0.01). KPC-KpBSIs developed in patients identified as KPC-K.pneumoniae carriers were treated with initial active therapy in 56% and 100% of cases in Period 1 and Period 2, respectively (p<0.01), consisting in active antibiotic combinations in 39% and 94% of cases, respectively (p<0.01). In Period 1, the 61% of KPC-KpBSI were breakthrough (fatal in the 73% of cases) while no breakthrough KPC-KpBSI was observed in Period 2 (p<0.01). Overall, KPC-KpBSI-related mortality was 88% with no initial active treatment, 11.5% with at least one initial active antibiotic (p<0.01), 9% with initial active combination. Only the initial active treatment resulted independently associated with survival. Conclusions. In high-risk patients with hematological malignancies colonized by KPC-K.pneumoniae, the empiric treatment of febrile neutropenia active against KPC-K.pneumoniae reduced KPC-KpBSI-related mortality to 6% and prevented fatal breakthrough KPC-KpBSI.