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  • 1
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2286-2286
    Abstract: Background. Epidemiological surveillance allows to detect emerging pathogens and antibiotic resistant strains and can provide guideline for an appropriate antibiotic policy. To this end we prospectively analysed all febrile/infectious episodes occurring at our Hematologic Unit during two consecutive 18-month periods from April 2004 to March 2007. Patients and Methods. Microbiological documented infections (MDI) were considered and correlated with the following variables: diagnosis of acute leukaemia, status of disease, neutropenia ( & lt;0.5 × 10^9/L), prophylaxis with levofloxacin, presence of central venous catheter (CVC). An infection was defined nosocomial when recorded after 48h from admission. Results. Of 773 febrile/infectious episodes during the surveillance period 310 were MDI were and 372 pathogens were isolated. Gram-negative (G−) bacteria represented 49.2% of all pathogens (183/372) and Gram-positive (G+) 41.1% (153/372), fungal pathogens 8.9% (33/372); the proportions remained stable over the two periods. Among G+, Stafilococci (50.3%) and Enterococci (25.5%) were the most frequent bacteria. Stafilococci, particularly S. aureus, were more frequent during the first period (49/76 vs 28/77, p=0.0007 and 27/76 vs 7/77, p & lt;0.0001 respectively), in non neutropenic patients (41/119 vs 36/191, p=0.0028) with uncontrolled disease (60/202 vs 17/108, p=0.0085). Enterococci were more frequent during the second period (14/76 vs 25/77, p=0.06) and in patients with uncontrolled disease (8/108 vs 31/202, p=0.049). Viridans Streptococci occurred almost exclusively during the second period (2.6% vs 14.3%, p=0.017). E. coli (48.6%) and Pseudomonaceae (27.3%) were the most frequent bacteria among G−. E. coli occurred homogenously during the two periods of observation and was associated with neutropenia (64/191 vs 25/119, p=0.02), prophylaxis (57/150 vs 20/93, p=0.007) and presence of CVC (75/237 vs 14/73, p=0.04). Pseudomonaceae increased during the second period (33/97 vs 17/86, p=0.032). MR frequency (68%) was constant during the two periods and was associated with controlled disease (p=0.009) and prophylaxis (p=0.0067). FqR frequency, evaluated for Enterobatteriaceae and Pseudomonas spp (n=123), was 69.3%; it was constant and associated only with levofloxacin prophylaxis (p & lt;0.0001). Vancomicin-resistant Enterococci (VRE) increased during the second period from 21.4% to 32%. Four multiresistant Pseudomonas were observed, all during the last 12 months of observation. Multiresistant strains occurred exclusively as nosocomial infections, whereas there was no statistically significant difference in the frequency of FqR and MR strains between community-acquired and nosocomial isolates. Conclusions. The high frequency of MR and FqR also among community-acquired infections, as well as the emergence of Enterococci, viridans Streptococci and Pseudomonaceae with antibiotic multiresistance, point to the widespread use of prophylaxis and the inappropriate use of antibiotics as the possible main causative factors which should be reconsidered.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4488-4488
    Abstract: Background. Mitoxantrone is an anthracenedione derivative with cytostatic and immunomodulatory activity, which is licensed for worsening multiple sclerosis (MS), an autoimmune central nervous system disease. The occurrence of acute promyelocytic leukaemia (APL) following mitoxantrone therapy in MS has been sporadically reported, but its actual incidence and clinical outcome need further definition Aims and Methods. Among 1050 patients with a diagnosis of MS followed at our Institution since 1985, the clinical records of those receiving mitoxantrone were reviewed, in order to clarify the incidence of secondary APL as well as its clinical characteristics and outcome. Results. Since 1990, 98 patients affected by MS were treated with mitoxantrone, in most cases as third-line treatment after corticosteroids and interferon therapy. Four patients (M/F: 1/4) developed APL. Median age at presentation was 57.5 year (range 47–59), significantly higher than that of unselected MS patients. APL developed a median of 55.5 months (range 3766 mo) after the first course of mitoxantrone. The median total dose of mitoxantrone was 149 mg (range 35–234 mg), delivered over a median of 7 courses (3–13). The cumulative number of years of follow-up after the start of mitoxantrone was 690. Therefore the risk of developing APL in this cohort was 5.8‰. All but one patients were classified as low-risk APL according to the GIMEMA/PETHEMA scoring system, the fourth being intermediate-risk. Morphology was FAB M3v in 1 case, and classic in the remaining. Typical chromosomal translocation t(15;17) was observed in all patients as well as PML/RAR-α molecular rearrangement, of bcr1 type in all. Flt-3 mutation was always absent. Given the treatment-related pathogenesis of APL, a modification of the AIDA2000 treatment program was used, with a reduced dose of idarubicin during induction in 2 patients. The second consolidation course with mitoxantrone was avoided by repeating the first course twice. Complete hematologic and cytogenetic remission was obtained after induction in all patients. Two patients are receiving consolidation. Molecular response was documented after consolidation in the other two patients. Both of them relapsed. The first had molecular relapse after 4 months; he was treated with ATRA and Ara-C and obtained a second molecular remission, lasting 50+ months. The second patient showed a morphological relapse after 5 months. She was treated with arsenic trioxide obtaining a second complete morphologic and molecular remission, but relapsed 1 month after autologous peripheral stem cell transplantation given for consolidation. She is currently on reinduction therapy with arsenic trioxide, 26 months after diagnosis. Conclusions. APL is a rare hematological disease, but its incidence among mitoxantrone-treated MS patients is significantly increased, like in patients with malignant diseases treated with mitoxantrone. Age is a major risk factor for the development of mitoxantrone-related APL. Analysis of further potential risk-factor is ongoing. The clinical outcome of this subset of patients seems worse than in de-novo APL. The use of anthracyclines as part of the treatment program needs further evaluation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2528-2528
    Abstract: Background. Outcome of HIV-associated NHL (HIV-NHL) with adverse prognostic features is not satisfactory with standard therapy. High dose therapy (HDT) and autologous stem cell transplantation (ASCT) has proven safe and active in HIV-NHL in salvage setting. Aims. To define the role of HDT and ASCT in the upfront treatment of HIV-NHL at high risk, in terms of efficacy and toxicity. We report the mature results of a multicenter prospective study including HDT and ASCT as consolidation after first-line treatment of HIV-NHL at high-risk. Patients and methods. Inclusion criteria: untreated aggressive HIV-NHL (including DLBCL, plasmablastic, anaplastic lymphoma), aa-IPI 2-3, age 18-60, CD4+ count 〉 50/mcl and availability of effective HAART.. Patients (pts) received R-CHOP (no Rituximab for CD20 negative lymphoma) for 6 cycles and, if responsive, underwent stem cells collection after Cyclophosphamide 4gr/ms + G-CSF followed by HDT with BEAM and ASCT. Involved-field radiotherapy on previous bulky or residual disease was recommended. Patients (pts) received HAART during the entire treatment program. Results: From January 2007 to July 2014, 29 pts were registered and 25 entered the study. Median age was 48 years (range, 27-62). Nineteen pts had DLBCL, 5 plasmablastic, 1 anaplastic lymphoma. ECOG PS was 〉 1 in 14 pts (56%); Ann-Arbor stage III/IV, 7(28%)/18(72%); B symptoms, 16 (64%); LDH 〉 n.v., 18 (88%); aaIPI 2/3, 13 (52%)/12 (48%). Eighteen pts (72%) had a prior history of HIV-positivity, and 17 (68%) were on HAART at NHL diagnosis. In 7 pts HIV and NHL diagnosis were concomitant. Fourteen pts (56%) had detectable HIV-viremia (range 40- 〉 500.000 cp/mL). Median CD4+ count was 255/mcl (51-571). Ten pts (40%) had HCV infection. Twenty-two pts received (R)-CHOP-21 and 3 pts with plasmablastic histology received CHOP-14. One pt is on treatment and 24/25 are evaluable for (R)-CHOP response. One pt died of hepatic failure and 1 due to cerebral hemorrhage, 2 had prolonged cytopenia (plus severe hepatic toxicity in 1) and 1 infectious complications that lead to withdrawal from the trial [however 1 achieved a complete remission (CR) and 2 died of progressive disease]; 19 pts completed (R)-CHOP according to the study: 14 had CR, 4 partial remission (PR) and 1 disease progression (PD). On an intention to treat basis: ORR 79.2%, CR 62.5%, PR 16.7%. Seventeen/18 pts collected stem cells (median CD34+ cells 7.4 x 10e6/Kg, range 2.6-10.1) and 1 failed mobilization. Two pts had early disease progression after collection, 1 did not receive HDT because of cardiac ejection fraction 〈 50% at evaluation before BEAM and 14 actually received ASCT according to the protocol. Lymphoma stage IV and aa-IPI 3 were significantly associated with the risk of not receiving ASCT (p.02 and p.03 respectively, Fisher exact test). HDT-related toxicities included 5 grade II, 5 grade III and I grade IV gastrointestinal toxicity and 2 grade II and 1 grade III hepatic toxicity. Prior to engraftment, 1 VZV infection, 1 Clostridium difficile colitis, 1 sigmoiditis, 1 CMV reactivation and 9 FUO were registered. There were no transplant-related deaths. One case of CMV reactivation, 1 bacterial pneumonia and no opportunistic infections were registered during subsequent observation. After a median f-up of 50 ms (2-89), 5-years OS and PFS of the entire series were 74.6% (+8.9%) and 70.9% (+9.2%), respectively (Figure 1). All transplanted pts (100%) are alive and relapse-free after a median of 38.5 ms (1-82) after transplant (Figure 2). Conclusions: This is the first prospective trial addressing the role of HDT and ASCT in first line treatment of HIV-LNH. Almost 60% of pts were able to complete the entire treatment program and the ASCT was well tolerated. The OS in this series of pts at high risk is satisfactory and no relapse occurred in pts who received ASCT, after a prolonged follow-up. Further improvement could result from an increase in the rate of patients who receive ASCT. HDT with ASCT seems an effective way to consolidate first response and improve outcome in HIV-NHL at high risk . Fig 1 Survival from study entry (25 pts) Fig 1. Survival from study entry (25 pts) Fig 2 Survival after transplant (14 pts) Fig 2. Survival after transplant (14 pts) Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 154-154
    Abstract: Abstract 154 Background Follicular lymphoma (FL) has an indolent course during which patients (pts) receive multiple lines of active treatments ranging from single-agent chemotherapy (CHT) or monoclonal antibodies (MoAb), to high-dose therapy with stem cell transplantation (HSCT). In relapsed patients the efficacy of salvage treatments may be affected by the type and the intensity of the previous treatments and it is currently not known whether a definite sequence of treatments throughout the course of the disease could optimize the outcome of patients. Since randomized trials can hardly be designed to answer this important clinical question, the Fondazione Italiana Linfomi (FIL) launched an observational, multicenter, retrospective study (REFOLL) to analyze if combinations of different first-line and salvage treatments could be identified, able to achieve a better long-term outcome. Patients and Methods Of 582 pts with FL at first relapse between 2000 and 2008 registered from 25 Institutions, 548 were included in the study. They had received either alkylating- (AA) (22%), or anthracycline- (AC) (61%) or nucleoside analogues-based (NA)(17%) CHT as first-line treatment, with the addition of rituximab (R) in 284 (52%). AA pts were older (P 〈 .001), but they had less stage III-IV (P=.011) and FLIPI high-risk disease (P=.02), and had received maintenance R after first-line CHT more often (P 〈 .001) compared to pts receiving AC- or NA-based CHT. At relapse 21 pts received radiotherapy and 4 palliation and were excluded. Salvage treatment of the other 523 pts were either the same first-line CHT programs (AA: 20%; AC 18%; NA: 14% of the 523 pts, respectively) in 271 pts, associated with R in 73%, or a program including autologous HSCT in 151 (29%), or MoAb/radioimmunoconjugate without CHT in 101 (19%). The primary endpoint of the study was time to next treatment (TTNT) after relapse. Progression-free survival after relapse (PFS) and overall survival (OS) were secondary endpoints. Results The median follow-up after first relapse was 41 months (range 1–122) and the median TTNT (50%) was 41 months (CI95% 35–47 months). Among first-line treatments, AC+/−R was associated with a better TTNT after any salvage than AA+/−R or NA+/−R (HR: 0.71, P=0.007; HR: 0.73, P=0.021 after adjustment by age, stage and year of diagnosis). The addition of R to first-line CHT did not adversely impact on the efficacy of salvage treatments (P=0.156). As salvage treatment, auto-HSCT had a significantly better outcome when compared to any other program +/−R (HR ranging from 1.79 to 2.40). Patients receiving auto-HSCT were younger (P 〈 0.001), had a shorter duration of first remission (P=0.012), but the efficacy of HSCT was not affected by these two parameters. ASCT program included R in 63% and was followed by R maintenance in 7% of pts. Considering the combinations of first-line and salvage treatments received, using multiple Cox regression, the TTNT after relapse was significantly better in pts receiving first-line anthracycline CHT +/−R followed by auto-HSCT as salvage (HR ranging from 1.88 to 3.3 compared to any other sequence, including AA/NA CHT followed by auto-HSCT). Other factors independently influencing TTNT after HSCT were R maintenance (HR: 0.66), duration of first remission 〉 12 months (HR: 0.8), and stage III-IV at diagnosis (HR: 1.89). PFS after relapse was 35% at 5 years, superimposable to TTNT (36% at 5 years); in fact treatment sequences had the same effects on PFS as on TTNT. Overall survival from diagnosis was 89% at 5-yr (CI95% 85–91%) and the sequences CHT- 〉 HSCT and CHT- 〉 CHT with R showed a better outcome than CHT - 〉 CHT without R (HR:0.55, P=0.015; HR 0.61, P=0.047 after adjusting by age and stage at diagnosis). Conclusions Auto-HSCT obtained the best TTNT after relapse compared to any other regimen but its efficacy was maximized when anthracycline-containing CHT was used as first-line treatment, compared to other CHT programs. The addition of R to first-line CHT did not adversely impact on the results of any salvage. This study supports the concept that different sequences of active treatments do not necessarily obtain similar long-term results, which is important in the management of indolent diseases like FL and warrants further studies. The sequence of AC-CHT at diagnosis and auto-HSCT at relapse may be tested as the reference sequence of active treatments in FL patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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