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  • 1
    In: European Journal of Haematology, Wiley, Vol. 79, No. 5 ( 2007-11), p. 455-461
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 2027114-1
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  • 2
    In: The Lancet, Elsevier BV, Vol. 400, No. 10365 ( 2022-11), p. 1767-1776
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 3
    In: Colloids and Surfaces B: Biointerfaces, Elsevier BV, Vol. 220 ( 2022-12), p. 112931-
    Type of Medium: Online Resource
    ISSN: 0927-7765
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1500523-9
    SSG: 12
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  • 4
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 348-348
    Abstract: Gene expression profiling has been used to distinguish two major subtypes of diffuse large B cell lymphoma (DLBCL), termed germinal center B cell-like (GCB) DLBCL and activated B cell-like (ABC) DLBCL. Following CHOP-like chemotherapy, GCB and ABC DLBCLs had distinct 5-year survival rates of ∼60% and ∼30%, respectively. Prognostic gene expression signatures in CHOP-treated DLBCL include the lymph node signature, which reflects a non-malignant host response, the MHC class II signature, both favorable when expressed and the proliferation signature which is adverse when expressed. The addition of rituximab to CHOP chemotherapy (R-CHOP) has significantly improved the outcome for DLBCL patients. We therefore investigated, if gene expression signatures that predicted survival among DLBCL patients treated with CHOP remained predictive for DLBCL patients treated with R-CHOP. Gene expression profiling was performed on 156 samples from previously untreated patients with DLBCL using Affymetrix U133 plus arrays. All patients received rituximab and CHOP-like chemotherapy. Samples were classified as GCB DLBCL, ABC DLBCL, or unclassified, and were assessed for expression of the lymph node and proliferation signatures. A Cox-proportional hazards model was used to determine the association of these gene expression features with overall survival (OS). 71 DLBCL samples were classified as GCB DLBCL, 63 as ABC DLBCL, and 22 were unclassified. The addition of rituximab improved OS for both GCB and ABC DLBCL compared to historical controls treated with CHOP-like chemotherapy alone. After a median follow-up of 2.3 years, GCB DLBCL had a more favorable OS than ABC DLBCL, with 3-year OS rates of 86% vs. 68% (p = 0.014). The 3-year OS rate of unclassified DLBCLs was 69%. The lymph node signature was associated with favorable OS (p = 0.023) and the proliferation signature with inferior OS (p = 0.009), whereas the MHC class II signature was not associated with OS (p = 0.44). In summary, addition of rituximab to CHOP-like chemotherapy improved OS for both GCB and ABC DLBCL but ABC DLBCL remained inferior to GCB DLBCL. The prognostic value of the lymph node and proliferation signatures were maintained in the context of R-CHOP therapy. An understanding of the biological attributes of DLBCL tumors that are reflected in these gene expression signatures remains critical to our ability to improve survival of these patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    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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  • 5
    In: Trials, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-04-05)
    Abstract: Cluster randomised controlled trials (cRCT) present challenges regarding risks of bias and chance imbalances by arm. This paper reports strategies to minimise and monitor biases and imbalances in the ChEETAh cRCT. Methods ChEETAh was an international cRCT (hospitals as clusters) evaluating whether changing sterile gloves and instruments prior to abdominal wound closure reduces surgical site infection at 30 days postoperative. ChEETAh planned to recruit 12,800 consecutive patients from 64 hospitals in seven low-middle income countries. Eight strategies to minimise and monitor bias were pre-specified: (1) minimum of 4 hospitals per country; (2) pre-randomisation identification of units of exposure (operating theatres, lists, teams or sessions) within clusters; (3) minimisation of randomisation by country and hospital type; (4) site training delivered after randomisation; (5) dedicated ‘warm-up week’ to train teams; (6) trial specific sticker and patient register to monitor consecutive patient identification; (7) monitoring characteristics of patients and units of exposure; and (8) low-burden outcome-assessment. Results This analysis includes 10,686 patients from 70 clusters. The results aligned to the eight strategies were (1) 6 out of 7 countries included ≥ 4 hospitals; (2) 87.1% (61/70) of hospitals maintained their planned operating theatres (82% [27/33] and 92% [34/37] in the intervention and control arms); (3) minimisation maintained balance of key factors in both arms; (4) post-randomisation training was conducted for all hospitals; (5) the ‘warm-up week’ was conducted at all sites, and feedback used to refine processes; (6) the sticker and trial register were maintained, with an overall inclusion of 98.1% (10,686/10,894) of eligible patients; (7) monitoring allowed swift identification of problems in patient inclusion and key patient characteristics were reported: malignancy (20.3% intervention vs 12.6% control), midline incisions (68.4% vs 58.9%) and elective surgery (52.4% vs 42.6%); and (8) 0.4% (41/9187) of patients refused consent for outcome assessment. Conclusion cRCTs in surgery have several potential sources of bias that include varying units of exposure and the need for consecutive inclusion of all eligible patients across complex settings. We report a system that monitored and minimised the risks of bias and imbalances by arm, with important lessons for future cRCTs within hospitals.
    Type of Medium: Online Resource
    ISSN: 1745-6215
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2040523-6
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  • 6
    Online Resource
    Online Resource
    Hindawi Limited ; 2012
    In:  Advances in Hematology Vol. 2012 ( 2012), p. 1-10
    In: Advances in Hematology, Hindawi Limited, Vol. 2012 ( 2012), p. 1-10
    Abstract: Diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) accounting for approximately 30% of new lymphoma diagnoses in adult patients. Complete remissions (CRs) can be achieved in 45% to 55% of patients and cure in approximately 30–35% with anthracycline-containing combination chemotherapy. The ageadjusted IPI (aaIPI) has been widely employed, particularly to “tailor” more intensive therapy such as high-dose therapy (HDT) with autologous hemopoietic stem cell rescue (ASCT). IPI, however, has failed to reliably predict response to specific therapies. A subgroup of young patients with poor prognosis exists. To clarify the role of HDT/ASCT combined with rituximab in the front line therapy a longer follow-up and randomized studies are needed. The benefit of HDT/ASCT for refractory or relapsed DLBCL is restricted to patients with immunochemosensitive disease. Currently, clinical and biological research is focused to improve the curability of this setting of patients, mainly young.
    Type of Medium: Online Resource
    ISSN: 1687-9104 , 1687-9112
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2494501-8
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  • 7
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3890-3890
    Abstract: Abstract 3890 Introduction: Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy. Nevertheless a small proportion of patients with localized stage do not respond to therapy and progressed. We want to explore the predictive value on therapy outcome of an early evaluation of treatment response by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan performed after two corses of ABVD in pts with localized Hodgkin's disease. Patients and methods: From 2002, 246 new localized stage cHL pts were consecutively admitted to twelve Italian hematological centers on behalf of Intergruppo Italiano Linfomi. Pts with stage I-IIA according to Ann Arbor stage, independent of presence of bulky disease, were considered for the study. FDG-PET was mandatory at baseline, after two cycles and at the end of therapy. International Harmonization Project (IHP) interpretation criteria were recommended to define PET positivity. We evaluated the progression free survival of pts starting from the time of diagnosis to relapse or progression of disease or last follow-up. No treatment variation based only on PET-2 results was allowed. All bulky-disease pts reports were centrally reviewed. Results: The median age was 33 years (13-78), 133 pts were female, 225 pts were stage II, bulky was reported in 76 pts, 231pts were treated with combined modality and 15 pts were treated with chemotherapy alone. The FDG-PET performed after two cycles (PET2) was positive in 32 pts (13%). Seventeen non-bulky pts were PET2 positive: 10 (59%) progressed or relapsed and 7 remained in CR. By contrast 152/153 (99%) non-bulky pts with a negative PET2 remained in CR. Thus the PPV value of a PET2 in non-bulky pts was 59% and the NPV was 99%, moreover the sensitivity and specificity of PET2 were 91% and 96%, respectively. In bulky disease pts we performed a revision of all reports according to Deauville criteria and 3 cases were converted from PET2 positive to PET2 negative. In revised bulky disease pts 15 were PET2 positive: 6 (40%) progressed or relapsed and 9 remained in CR. In this group of pts the PPV was 40%, the NPV 93% and sensitivity and specificity were 60% and 90% respectively. In univariate analysis negative FDG-PET performed after two cycles (p .0000), absence of bulky disease at diagnosis (.005) were statistically correlated with a better progression free survival. In multivariate analysis only PET2 was independently predictive of relapse/progression probability (p .000). With a median follow-up of 35 months (range 4–87), the 2-yr FFS probability for PET2 negative and for PET2 positive non-bulky patients were 98% and 29% respectively (p: .000) for patients with bulky-disease were 99% and 45% respectively (p: .002). Conclusion: This multicentric study confirms that FDG-PET scan performed after two courses of conventional standard dose chemotherapy was able to predict treatment outcome in early stage non-bulky cHL. In bulky disease we suggest new interpretation criteria to define interim PET results. Disclosures: Vitolo: Roche: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    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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  • 8
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4441-4441
    Abstract: Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive diseases characterized by poor prognosis. At 5 years, only 25 to 45% of patients treated with standard-dose chemotherapy are still alive. Retrospective studies show that patients with disease responsive to conventional-dose chemotherapy obtain durable remission after myeloablative treatment with autologous peripheral blood stem-cell (PBSC) support. This treatment strategy seems more effective when employed in untreated rather than relapsing patients. We present a series of 13 PTCL pts treated upfront (10 pts) or at the time of relapse-progression (3pts) with a 3 phase sequential therapeutic program including induction, intensification and consolidation treatment. The latter consisted of a myeloablative drug combination with PBSC support. Patients and methods: The median age of the 13 patients was 51 years (25–69). Histology was: PTCL-unspecified in 6 (46%) pts, anaplastic large cell lymphoma in 5 (38%), angioimmunoblastic and enteropathy-type T-cell lymphoma in 1 (8%) and 1 (8%) pt. Nine cases presented with advanced (III–IV) Ann Arbor stage and 2 had bulky disease. Nine cases complained B symptoms and 10 had high LDH levels. Six pts presented an intermediate-high IPI score (≥3 risk factors). Induction therapy consisting of dose-dense, dose-intense megaCEOP (1200mg/sqm cyclophosphamide, 110mg/sqm epirubicin, 1,4mg/sqm vincristine and 100mg prednisone) regimen was employed in 9 pts. Conventional dose CHOP or MACOP-B or P-VEBEC scheme was given in 2, 1 and 1 patient, respectively. Intensification treatment consisted of MAD (8mg/sqm mithoxantrone, 4g/sqm ARA-C, 40mg/die desamethasone) in 9 cases, 7g/sqm of cyclophosphamide in 1 patient and DHAP (100mg/sqm cisplatin, 4g/sqm ARA-C, 40mg/die desamethasone) in 3 cases. Three hundred mg/sqm carmustine, 100mg/sqm etoposide, 200mg/sqm cytosine arabinoside, and 140mg/sqm melphalan (BEAM) was used as myeloablative chemotherapy in all patients except for one who received mithoxantrone (60mg/sqm) and melphalan (180mg/sqm) as conditioning. Results: All patients completed the first 2 phases of the therapeutic program. Post-intensification disease status was complete remission (CR) in 4 (31%) pts, CRu in 2 (15%), partial remission (PR) in 5 (38%), stable disease (SD) in 1 (8%) or progressive disease (PD) in the last 1 (8%). Ten (77%) pts completed the whole treatment program, while 3 pts did not receive transplant because of insufficient stem cell harvest (1), progressive disease (1) or unacceptable peripheral and autonomic neuropathy due to MAD in 1 CR pt. After autologous PBSC transplantation, PR-to-CR conversion was observed in 3 cases and a total 7 of 10 (70%) transplanted pts achieved a CR. The median duration of overall objective response (8 CR, 2 PR) was 19 months (3–65) in the whole patient group, while it was 20 months (6–65) in transplanted pts. With a median follow-up of 26 months (9–83) from diagnosis 5 of the 13 pts (39%) are alive. These ones are the 5 pts in CCR after transplantation. No transplant-related mortality was observed. Eight (61%) pts died as a result of disease progression (6), infectious complications (1 in PR), or secondary acute myeloid leukemia (1). Median survival was 27 (9–82), 33,5 (18–82) and 40,5 (23–82) months for the overall cohort, the 10 transplanted pts and the 8 CR cases (7 transplanted and 1 not transplanted), respectively. Conclusion: disease status at transplant appeared to be the major factor that impacted outcome in our series. Although in a small number of patients, our data suggest that frontline autologous PBSC transplantation consolidation is feasible and may improve treatment outcome for chemosensitive PTCL patients.
    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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  • 9
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4784-4784
    Abstract: INTRODUCTION. Continously improving results have been obtained during the last two decades in the control of Philadelphia chromosome (Ph’) positive chronic myeloid leukemia (CML). However, the final goal of molecular remission remains difficult to be obtained, even in the imatinib era. AIMS: Evaluation of the rate of long lasting molecular remission (undetectable p210 transcript at RQ-PCR confirmed by NESTED/RT-PCR in at least two subsequent tests performed over a period of 12 months or more) in response to imatinib or to imatinib-IFNa combination employed as first, second or subsequent line of therapy. PATIENTS. Imatinib alone or in combination with IFNa was given as first, second or subsequent line of therapy to a total of 47 patients. In particular, twenty-one patients were treated at the time of diagnosis with imatinib alone (18,G1) or imatinib-pegilated IFN combination (3,G2). Twenty-three additional patients (G3) received imatinib as second line therapy. Finally, 11 patients were treated with the imatinib-IFNa combination as second (5,G4) or third (6,G5) line therapy. In details, G4 consisted of three patients in cytogenetic relapse (3) or no response (2) after first line imatinib (1)or IFNa-ARA-C(1)therapy. All six patients included in G5 were complete kariotypic, but not molecular responder to imatinib given as second line treatment. METHODS. Molecular response was evaluated by NESTED/real-time-PCR (Guo JQ et al.; Leukemia : 2002; 15:2447–53) and real-time quantitative-PCR (Gabert J et al. Leukemia : 2003; 17: 2318–57) time intervals of 3–6 months from the beginning of therapy. RESULTS. A complete molecular remission lasting 12 months or more was obtained in 11 of 42 evaluable patients(therapy duration ≥ 18 mths).The response rate was higher in patients receiving the imatinib-IFNa combination(6/14) than in those given imatinib in monotherapy (5/36).In details, 4/14 and 1/3 patients respectively receiving early imatinib or imatinib-IFNa combination achieved a stable molecular remission. Two to four consecutive negative tests were documented in all five cases over a period ranging from 12 to 19 mths with 4 patients still in continous remission. Furthermore, 1/22 and 5/11 patients obtained a complete molecular response to imatinib given as second line therapy or imatinib-IFNa combination employed as second (4) or third (1) line therapy. Five negative tests were documented over a period of 12 mths in the patient responsive to imatinib monotherapy. Three to 7 negative consecutive tests were obtained during a period of 12 to 36 mths in the remaining five cases while receiving the imatinib-IFN-a combination. At the present time, 5 of these 6 patients are in continous molecular remission. In all molecularly responsive patients, stable molecular remission was usually preceded by a period of fluctuating negative-positive results of NESTED-PCR tests. CONCLUSIONS. It is not possible to achieve any firm conclusion regarding the effect of the imatinib-INFa combination on molecular response because of the small sample size of treated patients. However, our findings suggest an additive effect of imatinib and IFNa in Ph’ clone control as indicated by the improvement of the quality of remission in long lasting kariotypically, but not molecularly responsive patients when this combination therapy was utilized.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    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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  • 10
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1450-1450
    Abstract: Background: Hodgkin’s lymphoma is one of the maligant diseases with the highest rate of cure particularly if diagnosed in early stage. Nevertheless a small proportion of patients with localized stage do not respond to therapy and become chemorefractory. FDG-PET clearly showed the high predictive value in identifing patients with bad prognosis in advanced stages. The aim of this prospective study was to evaluate the prognostic value of FDG-PET in patients with localized Hodgkin’s disease. Patients: From 2002, 122 new localized stage Hodgkin’s lymphoma patients were consecutively admitted to seven Italian hematological centers on behalf of Intergruppo Italiano Linfomi. Patients with stage I-IIA according to Ann Arbor stage, independent of presence of bulky disease, were considered for the study. FDG-PET was mandatory at baseline, after two cycles (immediately before the start of the third cycle) and at the end of therapy. We evaluated the progression free survival of patients starting from the time of diagnosis to relapse or progression of disease or last follow-up. Patients were candidate to receive 3 or 4 course of ABVD followed by involved field radiotherapy at 30 Gy, except in the cases in which physician decided to omit radiotherapy due to excess of toxicity. All patients were given the planned therapy except in case of overt progression. All patients were treated with ABVD Results: The median age was 31 years (16–75), 63 patients were female and 59 male, 10 patients presented stage I and 112 stage II, bulky was reported in 29 patients. One-hundred and ten patients were treated with combined modality (CT+RT) and 12 patients were treated with chemotherapy alone (all with 6 cycles). One hundred and eleven patients attained CR while 11 were chemoresistent: 6 showed disease progression during CT and 5 showed an early relapse. The FDG-PET performed after two cycles (PET2) was positive in 18 patients (15%) and the FDG-PET performed at the end of therapy was positive in 12 patients. Fourteen patients showed disease progression during therapy or within 6 months after having reached CR, three patients died due to the disease. In univariate analysis negative FDG-PET performed after two cycles (p .0000), absence of bulky disease at diagnosis (.003) and the use of radiotherapy (.0006) were statistically correlated with a better progression free survival. In multivariate analysis only PET2 was independently predictive of relapse/progression probability (p .007). With a median follow-up of 29 months (range 6–79) 119 patients are alive and 108 (88%) are free from progression. The 2-yr FFS probability for PET2 negative and for PET2 positive patients were 95% and 46% respectively Conclusion: This prospective and multicentric study confirms that FDG-PET scan performed after two courses of conventional standard dose chemotherapy was able to predict treatment outcome in early stage Hodgkin disease.
    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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