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  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1615-1615
    Abstract: Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age ( 〈 60 or 〉 60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. 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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  • 2
    In: Hematological Oncology, Wiley, Vol. 31, No. 4 ( 2013-12), p. 213-217
    Abstract: Angioimmunoblastic T‐cell lymphoma (AITL) is characterized by an aggressive clinical course and unfavourable prognosis. Refractory AITL patients have very few treatment options. Lenalidomide has previously been reported to have clinical efficacy in this setting; however, long‐term reports are limited. A 59‐year‐old man was referred to the hospital with fatigue, skin rash, weight loss and generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B with bone marrow involvement. The patient had an unsatisfactory response despite three lines of conventional chemotherapy and radiotherapy. The patient received lenalidomide monotherapy (25 mg once daily) on days 1 to 21 of every 28‐day cycle for six cycles, followed by maintenance therapy with six cycles of lenalidomide 15 mg once daily on days 1 to 21 of every 28‐day cycle. A computed tomography scan was assessed before lenalidomide treatment, after the third cycle, at disease restaging 2 months after completion of the induction phase, every 3 months during the maintenance phase and every 6 months during the follow‐up period. At the last evaluation, after a follow‐up of 30 months, the patient maintained a clinical and radiological complete response. The treatment was well tolerated with manageable toxicity. Lenalidomide treatment demonstrated for the first time in the literature impressive and long‐term clinical efficacy in a heavily pretreated chemorefractory AITL patient. Copyright © 2012 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0278-0232 , 1099-1069
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2001443-0
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  • 3
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3174-3174
    Abstract: Hairy cell leukemia (HCL) is a rare B-cell neoplasm generally responsive to Cladribine. Cladribine is generally administered intravenously either as a continuous weekly infusion or as a 2-hour daily or weekly infusion for 7 days. Subcutaneous Cladribine is an alternative route with 100% bioavailability and with efficacy similar to intravenous 2CdA at the dose of 0.7 mg/kg/cycle. In indolent non-Hodgkin lymphomas other than HCL, reduction to 0.5 mg/kg/cycle determined equivalent efficacy and lower toxicity. In a national multicentre clinical trial (protocol EudraCT code: ICGHCL 2004), we have evaluated efficacy and toxicity of subcutaneous Cladribine given 0.1mg/kg/die for 5 (total dose 0.5 mg/kg, arm A) or for 7 days (total dose 0.7 mg/kg, arm B) as a single course in newly diagnosed HCL requiring treatment. Responses to treatment were assessed on day 60 and day 180 after treatment and defined according to the 1987 Consensus criteria. Complete Remissions (CR) and Partial Remissions (PR) were considered as beneficial responses, while minor Responses (mR) and No Responses (NR) were rated as treatment failures. Toxicity was assessed from day 0 to day 60 after treatment, according to the 2003 NCI/CTCAE v3 criteria. In this interim analysis, 92 of the 132 patients currently recruited (45 patients in arm A and 47 in arm B) were evaluated for toxicity and response to treatment. 2CdA was administered at the proposed regimen with no modifications in all patients. Eighty-five of 92 patients (92%) had a beneficial response to treatment (57/92 CR, 62%; 28/92 PR, 30%). The 7/92 treatment failures scored as 3/92 mR (3%) and 4/92 (5%) NR. Responses were equivalent in the two arms (p=0.7), with 41/45 (91%) beneficial responses (27/45 CR, 60%; 14/45 PR, 31%; 2/45 mR, 4% and 2/45 NR, 4%) in arm A versus 44/47 (94%) beneficial responses in arm B (30/47 CR, 64%; 14/47 PR, 30%; 1/47 mR, 2%; 2/47 NR, 4%). Overall grade 3–4 toxicity was recorded in 16/92 (17%) patients (8/92 FUO, 9%; 4/92 documented infections, 6%, 3/92 skin rashes, 3%; 1/92 hepatic toxicity, 1%) and appeared less frequent in arm A (4/45, 9%) than in arm B (12/47, 25%) (p=0.05). Analysis of distribution of toxicities in the two arms (arm A: 2/45 FUO, 4%; 0/45 documented infections; 1/45 skin rash, 1%; 1/45 hepatic toxicity, 1%; arm B: 6/47 FUO, 13%; 4/47 documented infections, 9%; 2/47 skin rashes, 4%) revealed a significantly lower frequency of FUO and infections in arm A (2/45, 4%) than in arm B (10/47, 22%) (p=0.02), to suggest a higher risk of infection in the 7 day regimen. The present data indicate that overall activity of subcutaneous 2CdA is similar to the intravenous formulation (Cheson, 1998). Furthermore, the current interim analysis suggests that subcutaneous 2CdA given at 25% reduced doses (0.5 mg/kg) has equivalent activity and lower toxicity than subcutaneous 2CdA at standard doses (0.7 mg/kg) and is easy to give in an outpatient setting.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4826-4826
    Abstract: Abstract 4826 Background: Hodgkin Lymphoma (HL) is a highly curable malignancy that mostly affects young adults; currently, considering all patients more than 75% of them will be cured and the ones diagnosed with early stage disease have a chance of cure over 90%. However, despite these very satisfactory results, about 20% of patients still die from progressive disease and non-specific related Hodgkin's mortality, mostly due to late toxic effects, continues to rise with time. Consequently, the optimal treatment should be designed based on prognostic models, but currently all of them predict the outcome of treatment with imperfect accuracy. Since from recent studies “early FDG–PET” and lately tissue macrophages infiltration seem to be powerful predictors, we hypothesized that macrophage infiltration could be the shadow of the inflammatory microenvironment that FDG-PET identifies in HL and that persist at early assessment in patients who will fail to respond to treatment. Consequently we decided to verify this hypothesis analyzing a group of patients with HL diagnosed and treated at our institution. Patients and methods: on the basis of availability of paraffin embedded diagnostic specimen and “early PET” assessment, we selected a cohort of 24 patients (M/F: 12/12) with Hodgkin Lymphoma, diagnosed and treated at our institution between February 2007 and February 2010. Before starting treatment all patients completed staging with whole body CT scan, FDG-PET and bone marrow biopsy. Ten patients had stage II disease, 10 patient stage III and 4 patients stage IV; median age was 33 years. Programmed treatment consisted of 4–6 cycles of ABVD and, if indicated, involved-field radiation therapy. Patients repeated CT scan and FDG-PET after two cycles and after completion of therapy. Macrophage infiltration in paraffine-embedded diagnostic specimen was retrospectively determined by immunohostochemistry. Results: After two cycles of ABVD, FDG-PET was negative in 18/24 patients (75%), while FDG-PET was positive in the six remaining patients (25%). Overall 20 out of 24 patients (83%) achieved a CR, however two of them had an early relapse (within 6 months), so they underwent 2nd line therapy plus autologous stem cell transplantation (ASCT), both obtaining a second CR. Among the four remaining patients, one achieved only a PR and entered salvage protocol with 2nd line treatment plus ASCT, two achieved a CR after second line treatment and the last one was refractory to 3 lines of treatment and finally was enrolled in an investigational protocol. With a median follow up of 18.5 months, 21 out of 24 patients are alive in CR, a patient is alive in PR and two patients died, due respectively to pulmonary thromboembolism and ARDS (after mediastinal irradiation). Five out six patient (83%) with persistent positive “early FDG-PET” failed their first line treatment. About macrophage percentage in the diagnostic specimen, evaluated and classified according to the criteria reported in the recent paper by Dr Steidl and coworkers, one patient (4%) was classified with score 1, twelve (50%) with score 2 and eleven (46%) with score 3. Among the six patients with persistent positive “early-FDG-PET”, one of them had score 1 (and never obtained CR), three had score 2 and two score 3. Conclusions: with the limitation of a small cohort of patients and the lack of gene-expression assays, our data do not seem to support our hypothesis neither to confirm the recently reported prognostic impact of macrophage infiltration in diagnostic specimen. 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: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Leukemia Research and Treatment, Hindawi Limited, Vol. 2012 ( 2012-02-15), p. 1-4
    Abstract: Ph+ acute lymphoblastic leukemia (Ph+ ALL) is a high-risk acute leukemia with poor prognosis, in which the specific t(9;22)(q34;q11) translocation results in a chimeric bcr-abl (e1a2 breakpoint) and in a 190 KD protein (p190) with constitutive tyrosine kinase activity. The advent of first- and second-generation tyrosine kinase inhibitors (TKIs) improved the short-term outcome of Ph+ ALL patients not eligible for allo-SCT; yet disease recurrence is almost inevitable. Peptides derived from p190-breakpoint area are leukemia-specific antigens that may mediate an antitumor response toward p190+ leukemia cells. We identified one peptide named p190-13 able to induce in vitro peptide-specific CD4+ T cell proliferation in Ph+ ALL patients in complete remission during TKIs. Thus this peptide appears a good candidate for developing an immune target vaccine strategy possibly synergizing with TKIs for remission maintenance.
    Type of Medium: Online Resource
    ISSN: 2090-3219 , 2090-3227
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2684657-3
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  • 6
    In: Acta Haematologica, S. Karger AG, Vol. 124, No. 1 ( 2010), p. 44-45
    Type of Medium: Online Resource
    ISSN: 1421-9662 , 0001-5792
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2010
    detail.hit.zdb_id: 1481888-7
    detail.hit.zdb_id: 80008-9
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  • 7
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1626-1626
    Abstract: Abstract 1626 Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies tested R-CHOP14 (C14). The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14. All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent were accrued. From January 2002 to December 2010, 123 pts were treated with C21 and 142 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age ( 〈 65 or 〉 64 years) with more aged pts in C21 arm (p 0.000), PS with more advanced PS (2–3) in C21 arm (0.000) and LDH value which was more frequently elevated in C14 arm (p: 0.002). After induction therapy 190 pts (71%) obtained a complete remission: 82/123 (67%) after C21 and 108/142 (75%) after C14. After a median period of observation of 31 months 81 pts relapsed, 42 (51%) in the C21 arm and 39 (36%) in the C14 arm. Considering the two therapies, C21 vs C14, no differences were reported in OS, PFS and DFS: 61% vs 68%, 59% vs 58% and 74% vs 61% respectively. In univariate analysis OS was lower in older pts (p: 0.02), advanced stage (p: 0.02), symptomatic disease (p: 0.05), elevated LDH (p: 0.001), bone marrow infiltration (p: 0.02) and intermediate or high risk IPI (p: 0.000); PFS was lower in advanced stage (p: 0.002), symptomatic disease (p: 0.009), elevated LDH (p: 0.001), bone marrow infiltration (p: 0.001) and intermediate high risk IPI (p: 0.000). In multivariate analysis OS was significantly better in low-intermediate IPI risk pts (p: 0.000) and in pts treated with C14 (p: 0.02); the PFS was better in low-intermediate IPI risk pts (p: 0.000). Considering only pts with low or low-intermediate IPI we observed that OS was significantly superior in the group treated with C14 (90% vs 64% p: 0.03), moreover in young pts ( 〈 65 years) OS was better in pts treated with C14 (81% vs 58% p: 0.05). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14, all pts but three (2%) completed the therapy without delay or dose reduction. No differences in extra-hematological toxicity were observed. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population but in a subset of pts, young and low/intermediate risk pts, the C14 scheme seems to improve the OS. We will enlarge the cohort of studied patients but further prospective randomized studies are needed to verify this preliminary observations. 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: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Scientific Data, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2020-11-19)
    Abstract: Single Particle Imaging (SPI) with intense coherent X-ray pulses from X-ray free-electron lasers (XFELs) has the potential to produce molecular structures without the need for crystallization or freezing. Here we present a dataset of 285,944 diffraction patterns from aerosolized Coliphage PR772 virus particles injected into the femtosecond X-ray pulses of the Linac Coherent Light Source (LCLS). Additional exposures with background information are also deposited. The diffraction data were collected at the Atomic, Molecular and Optical Science Instrument (AMO) of the LCLS in 4 experimental beam times during a period of four years. The photon energy was either 1.2 or 1.7 keV and the pulse energy was between 2 and 4 mJ in a focal spot of about 1.3 μ m x 1.7 μ m full width at half maximum (FWHM). The X-ray laser pulses captured the particles in random orientations. The data offer insight into aerosolised virus particles in the gas phase, contain information relevant to improving experimental parameters, and provide a basis for developing algorithms for image analysis and reconstruction.
    Type of Medium: Online Resource
    ISSN: 2052-4463
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2775191-0
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  • 9
    In: Cancer Genetics and Cytogenetics, Elsevier BV, Vol. 197, No. 1 ( 2010-2), p. 84-85
    Type of Medium: Online Resource
    ISSN: 0165-4608
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 2004205-X
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