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  • 1
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 18, No. 10 ( 2018-10), p. e401-e419
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2540992-X
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  • 2
    In: Journal of Investigative Dermatology, Elsevier BV, Vol. 142, No. 11 ( 2022-11), p. 3009-3019.e9
    Type of Medium: Online Resource
    ISSN: 0022-202X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 80136-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3050-3050
    Abstract: The neutrophil/lymphocyte ratio (N/L) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. An increase in the neutrophil count is a marker of inflammation which is an essential part of the neoplastic process. Conversely, a decrease of the peripheral lymphocyte count might reflect an impairment of the host defense mechanism associated with advanced and aggressive cancers. Since There are only few reports on the N/L ratio in non-Hodgkin lymphomas. We studied the prognostic role of the N/L ratio at diagnosis in 286 patients with diffuse-large-B-cell lymphoma (DLBCL) enrolled in a multicenter prospective registry of the Lazio region in Italy The median age at diagnosis was 69 years (27-91) and the female/male ratio was:141/145.First, we analyzed for associations between N/L ratio and patient characteristics. The optimal cut-off value for the N/L was obtained using the Receiver Operating Curve (ROC) and according to the published data in solid tumor. N/L ≥ 4 was significantly associated with presence of B-symptoms (p=0.01) and elevated LDH levels (p=0.007) at diagnosis. Most patients were treated with R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) or R-CHOP-like (90%). Complete Remission (CR) + Partial Remission (PR) were obtained in 210/286 (73%). The median follow up period was 15 months (range: 1-33 months): 27 patients died for lymphoma relapse/progression and 16 for other causes. Patients with N/L ≥ 4 experienced a higher rate of relapse, while N/L 〈 4 was associated to a significantly better Overall (OS, P 〈 0.05) and Event Free Survival (EFS, P 〈 0.01). (Figure 1, panel a and b).Furthermore, considering only patients with IPI score ≤ 3, those with N/L 〈 4, (Figure 1, panel c), had a better OS compared to those with N/L≥ 4 (P 〈 0.01). Conclusion: The N/L ratio may be a useful and unexpensive prognostic marker in patients with DLBCL. The inferior outcome observed in patients with N/L ≥ 4 might reflect an immune and inflammatory imbalance induced by a more aggressive tumor, releasing directly or indirectly inflammatory cytokines and/or inducing immune suppression or exhaustion. A link with inflammation is suggested by the correlation of N/L ratio ≥ 4 with high LDH levels and the presence of B symptoms. Figure 1. Panel A. Overall Survival (OS) and Panel B. Event Free Survival (EFS) by N/L ratio. Panel C. Overall Survival (OS) by N/L in patients with IPI score ≤ 3. Table 1.Baseline patients characteristics (N = 268) and compared by N/L 〈 4 or ≥ 4 by using Chi-Square Test for categorical variables. Abbreviations not included in the text: IPI = International Prognostic Index; LDH = lactate dehydrogenase, PD: Progression Disease, NA: Not Applicable. Disclosures Cimino: Celgene: Honoraria; Bristol-Mayer: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 4
    In: Cancer, Wiley, Vol. 104, No. 12 ( 2005-12-15), p. 2743-2752
    Abstract: The addition of rituximab to fludarabine in 60 symptomatic, untreated patients with B‐cell chronic lymphocytic leukemia (B‐CLL) categorized mainly as intermediate Rai stage, achieved both a higher complete remission (CR) rate (78%) and a longer progression‐free survival (PFS) rate (68% at 3 yrs). However, significantly shorter CR and PFS rates were obtained in patients who had ZAP‐70‐positive B‐CLL (28 of 60 patients).
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2005
    detail.hit.zdb_id: 1479932-7
    detail.hit.zdb_id: 1429-1
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  • 5
    In: Leukemia Research, Elsevier BV, Vol. 39, No. 10 ( 2015-10), p. 1066-1070
    Type of Medium: Online Resource
    ISSN: 0145-2126
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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  • 6
    In: European Journal of Cancer Care, Wiley, Vol. 29, No. 1 ( 2020-01)
    Type of Medium: Online Resource
    ISSN: 0961-5423 , 1365-2354
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5655-5655
    Abstract: The front-line therapy for CLL young and fit patients is chemo-immunotherapy with Fludarabine-Cyclophosphamide and Rituximab (FCR). However, around three quarter of the patients with a newly diagnosed CLL are 65 years or older, with approximately 42% being older than 75 years and with age-related comorbidities. FCR regimen results in a significant myelosuppression and high rates of early and late infections. Hence, other less toxic regimens are under evaluation. Recently the German CLL study group reported an interim analysis of the CLL10 trial, who compared FCR vs Bendamustine-Rituximab (BR). The response rates to the 1st-line treatment with BR or FCR were comparable, and BR could be an alternative 1st-line treatment for medically fit pts. Notably, this study showed that pts treated with BR were often older (median 71 vs. 65 yrs; p 〈 0.0001) and frequently with comorbidities (67% vs. 62%), suggesting that it may be a suitable option for this wide subpopulation. Here we report retrospective data from 12 Italian centres focused on the evaluation of efficacy and safety of BR in elderly SLL/CLL patients. Data on 70 untreated SLL/CLL patients with age ≥ 65 years assigned to receive front-line therapy with 6 monthly courses of Bendamustine (90 mg/sm at days 1-2) and RTX (375 mg/sm at day 1 for the first course, then 500 mg/sm for subsequent cycles) were collected. The primary end points were the Overall Response (CR/PR) and toxicity rates. Responses, evaluated at 2 months after the end of therapy, were defined according to the updated National Cancer Institute-Working Group guidelines. Seventy patients (47 males and 23 females) with a median age of 72 years (range, 65-87 years) were included in the study. Eight patients (11.4%) were unfit (CIRS score =/ 〉 7). All patients had an ECOG performance status ranging from 0 to 2. Twenty-nine of 70 patients had Binet stage C, 12 patients were Binet A, 29 Binet B. Thirty-nine patients showed karyotype abnormalities at FISH analysis (data available in 54/70 patients). High risk FISH karyotype according to Döhner´s hierarchical model was detected in 17 patients (14 with del 11q, 3 with del 17p). Ten of them had del(13q14), 12 had trisomy 12 and 15 had normal karyotype. The analysis of the IGHV status, available in 50 patients, showed 25 patients with somatic mutation and 25 patients with germ-line sequences. Zap-70 data were available for 37/70 pts, 19 of them (51.3%) were Zap-70 positive. CD38 was available for 52 patients: it was positive in 27/52 pts (51.9%). (Table 1) A mean number of 5.46 courses of BR were given and the Bendamustine dose was reduced by more than 10% in 39 patients (55,7%). The main reason for dose reduction was haematological toxicities. The ORR rate was 88,6%,with 22 patients (31.4%) obtaining a CR and 40 patients (57,2%) obtaining a PR. Progression Free Survival, Time To Retreatment and Overall Survival rates at 2-years were 79%, 90.3% and 89.6%, respectively. Only the presence of del17 resulted to affect the response rate (p= 0.023) and PFS (p 〈 0.001). Grade 3-4 hematological toxicity was recorded in 25 patients (35,7%). Extra-hematological toxicity grade I-III (skin reactions, gastrointestinal and cardiovascular symptoms, infusion related reactions, etc). was noticed in 35 patients (50,0%). Eleven patients (15.7%) were admitted to the hospital. Retrospective data from this group of elderly CLL patients indicate that Benda-R front-line at standard dose provides a high response rate with a good safety profile, even if more than 50% of patients experienced a Bendamustine dose reduction until 70 mg/sm. Even in this cohort of patients we confirmed del17 as a bad prognostic parameter. Table 1: Patients’ clinical-biological characteristics. Median age at diagnosis 72 years (range 65-87) M:F 47/23 CIRS score =/ 〉 7 8/70 pts (11.4%) PB lymphocytes 33.203/mmc Binet stage A 12/70 pts (17.2%) Binet stage B 29/70 pts (41.4%) Binet stage C 29/70 pts (41.4%) ZAP70 〉 20% 19/37 pts (51.3 %) CD38 〉 30% 27/52 pts (51.9%) Beta2microglobulin increased 51/59 pts (86.4%) IgVH homology 〈 98% 25/50 pts (50%) Normal FISH 15/54 pts (27.8%) del 13q 10/54 pts (18.5%) +12 12/54 pts (22.2%) del 11q 14/54 pts (25.9%) del 17p 3/54 pts (5.6%) Bulky syndrome 16/70 pts (22.9%) PB, peripheral blood; IgVH, immunoglobulin heavy chain variable genes; FISH, Fluorescent In Situ Hybridization. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 8
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2564-2564
    Abstract: Abstract 2564 Background: Multiple myeloma (MM) accounts for about 14% of all newly diagnosed haematological cancers, and it is estimated that its incidence will rise considerably due to an increasingly aging population in the Western world. Treatment of myeloma has changed in the past decade leading to a possibility of reaching a complete remission (CR) of nearly 50%, a median survival of 5 years, and a 10-year survival rate of 20%. Most of the recent treatment strategies do not require hospitalization so that many patients spend a considerable amount of time at home managing all the difficulties related to the therapies often with little support. Even though this physically disabling and deteriorating condition has a great impact on patients, little is known about their (unmet) needs and quality of life (QOL). Aims and Methods: The purpose of this qualitative study was to identify dominant themes, links between domains of QoL from the patients' perspective and how these domains influence their expectations regarding QoL in patients with multiple myeloma, trying to identify possible interventional instruments. The sample consisted of 34 patients treated in 9 Italian Centres: 16 women and 18 men; median age 65 years (range 35–77); with a first diagnosis of MM between 1982 and 2009 (median time since diagnosis 3 years ). From July 2009 to Nov 2009, 34 indepth interviews (60 minutes each) were conducted by clinical psychologists. Data from individual interviews were audiotaped and transcribed and then analysed with the “Text Emotional Analysis”, a methodology based on clinical-psychological models and on statistical multivariate analysis techniques. Results: The analysis, conducted with the statistical software Alceste (Analyse des Léxèmes Cooccurrents dans les Enoncés Simples d'un Texte), highlighted 4 word clusters (Table 1: the words that characterize the clusters are reported in the table with a decreasing χ2 value that indicates the importance of the single words in the belonging clusters): Cluster 1 “The relationship with family and friends”; Cluster 2 “The relationship with pain and drugs”; Cluster 3 “The elaboration of the experience”; Cluster 4 “The relationship with physicians and the hospital”. The position of the different clusters in the factorial space can also originate a second kind of analysis that is based on the relation between clusters (Table 2: values of the relationships between Clusters and Factors). On the first factor, cluster 4 and cluster 1 oppose themselves. This is the factor of relationships: the new relationships (the physician and the hospital) oppose to the old relationships (the family); the socialization with the new environment (positively connoted: attention, professionalism, commitment, ability) that is in opposition with the isolation and the shelter of the family (children, family, wife, mother, home). On the second factor, Cluster 2 and Cluster 1 oppose themselves. This is the factor that highlights the complexity of the experience towards the body due to the disease and the drugs (pain, effects, improvements, results, care, discomfort). The third factor is characterized by cluster 3 and expresses coping strategies towards ones condition (shame, companion, emotions, to get accustomed to). Conclusion: This study shows that one of the most important aspects for patients affected by MM is the creation/reorganization of all relationships. The patient's psychological dimension that defines the relationship with the haematologist is driven by an “all-absorbing” taking in charge of the physician fantasy, that often clashes with the hospital practicality. The relationship with other patients, with others that live the same experience, so called “companion” (from latin cum panis, who eats the same bread). Moving on from the results of this research, in the period of May 2010-July 2010, a first intervention was performed. In 5 pilot centres seminars were conducted by clinical psychologists in order to let patients interact with their physicians in a dedicated “space” different from a waiting room or an informative seminar. More than 100 people participated between patients, family members, physicians and nurses. With the findings of this research a questionnaire will be designed and administered to a wider multiple myeloma patient sample. Disclosures: Pelagalli: Celgene: Research Funding. Boccadoro:Celgene, Janssen-Cilag: Consultancy, scientific advisory board, research support. Petrucci:Janssen-Cilag, Celgene: Honoraria.
    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
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  • 9
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3498-3498
    Abstract: In a remarkable proportion of adult AML patients (40–50%), no clonal abnormalities are found on standard cytogenetic analysis. In this group of patients, several gene mutations have been described, allowing to discriminate subgroups with distinct clinical outcome. Among these molecular signatures, FLT3, a receptor tyrosine kinase with important roles in hematopoietic stem/progenitor cell survival and proliferation, has been demonstrated to be mutated in about 1/3 of AML cases, identifying a subgroup of patients characterized by disappointing overall cure rates. Therefore, roughly 60% of patients with normal karyotype are not classifiable by this specific mutation. The purpose of the present study was to investigate, in this group of patients with no specific molecular signature the prognostic role of MRD as determined by multiparametric flow-cytometry (MPFC). We analyzed a group of 127 AML cases entered into the EORTC/GIMEMA protocols AML10/AML12 (age 〈 61yrs) or AML13/AML15/AML17 (age 〉 61 yrs). By applying the maximally selected log-rank statistics, the threshold discriminating MRD negative from positive cases was set at 3.5 x10−4 residual leukemic cells, a level that selected, at the post-consolidation time-point, two groups of patients with distinct prognosis. Seventy-two out of 127 (56%) had a normal karyotype. Among these 72, 53 were studied for FLT3 mutational status; in 13 (25%) a mutated variant of FLT3 was detected. Among the remaining 40 patients with normal karyotype and unmutated FLT3, 39 were evaluable for the MRD status at the post-consolidation time-point: 9 patients were MRD− and 30 MRD+. These two subsets showed a distinct outcome in terms of 5-years RFS (83 vs. 23%, p=0.031). Interestingly, the FLT3−MRD+ patients shared with those FLT3 positive a similar poor prognosis (Figure 1). In recent reports, the evaluation of outcome depending on FLT3 status has been integrated with the analysis of the mutated status of other genes: FLT3-mutated cases associated frequently with Nucleophosmin (NPM1) exon-12 gene mutations but rarely with other mutations. The favorable impact of NPM1 mutations on OS and EFS clearly emerged in the group of normal-karyotype AML without FLT3 mutations. In a subset of 44 patients of our series either the mutations were investigated; this combined analysis identified 8 out of 44 (18%) patients FLT3 unmutated/NPM1 mutated with a better outcome (5-years OS 50% and RFS 50%, respectively) as compared to FLT3 unmutated/NPM1 unmutated and FLT3 mutated patients, which was however poorer than that of FLT3 unmutated/MRD− cases (Figure 1). In conclusion, MRD determination at the post-consolidation phase may help at improving the prognostic assessment of AML patients lacking specific chromosomal and/or molecular lesions, allowing risk-adapted post remissional therapies to be designed with more accurate modalities. Figure Figure
    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
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  • 10
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5172-5172
    Abstract: Abstract 5172 The introduction of JAK-2 V617F mutation in the diagnostic process of patients with erythrocytosis has led to a better definition of Polycythemia Vera (PV) patients, who had the mutation in 〉 90% of cases: however, in the real-life many patients with otherwise unexplained Hb and Ht elevation and lack of JAK-2 V617F mutation are located in the gray zone of the so-called Idiopathic Erythrocytosis (IE). In order to highlight clinical features of patients with IE, we revised 247 patients with primary erythrocytosis (i.e. excluding cases with respiratory and/or severe cardiovascular diseases) diagnosed in 2 Hematological Institutions in Rome from 6/1985 to 12/2010 with a evaluable JAK-2 mutational status at diagnosis or during the follow-up. Were considered as “PV JAK-2 positive” all patients with presence of mutation V617F at diagnosis or during follow-up. Among the patients who resulted JAK-2 V617F negative, were considered as “PV JAK-2 negative” all patients classifiable as PV according to PVSG criteria (if diagnosed before 1/2002) or WHO 2002 criteria (if diagnosed after 1/2002): the remaining patients were classified as “IE”. With these criteria, 181 patients (73.2%) were PV JAK-2 positive, 26 (10.5%) PV JAK-2 negative and 40 (16.3%) IE: the main clinical features of these 3 groups at diagnosis and during the course of disease are summarized in the table.PV JAK-2 positivePV JAK-2 negativeIENo of patients1812640Male87 (48%)22 (84%)38 (95%)Median age yrs (IR)59.3 (49.7–68.5)47.9 (42.6–64.5)57.8 (44.2–65.9)Median WBC x 109/l (IR)10.0 (8.4–13.0)10.6 (6.3–12.5)7.3 (6.4–8.3)Median PLTS x 109/l (IR)481 (349–651)214 (189–344)205 (165–236)No with palpable spleen63 (35.0%)7 (27.0%)2 (5.0%)Previous thrombosis29 (16.0%)2 (7.6%)1 (2.5%)Thrombosis during disease32 (17.7%)1 (3.8%)4 (10.0%)Fibrotic/Blastic evolution12 (6.6%)00 Comparing the 3 groups for the above features, there was a very significative (p 〈 0.001) male predominance in both IE and PV JAK-2 negative vs PV JAK-2 positive patients: in addition, patients with PV JAK-2 negative were younger (p=0.017). Compared to patients with IE, myeloproliferative features were significantly more prominent in patients with PV JAK-2 positive [higher WBC (p 〈 0.001) and PLTS (p 〈 0.001) median values and higher number of patients with spleen enlargement (p 〈 0.001)]; furthermore, also patients with PV JAK-2 negative had higher WBC median value (p=0.008) and more cases with spleen enlargement (p=0.007) compared to patients with IE, but not higher PLTS median value (p=0.166). Previous thrombotic events were more frequent in PV JAK-2 positive patients vs patients with IE (p=0.032), while no difference was revealed among the 3 groups as to thrombotic events during follow-up and fibrotic/blastic evolution. In conclusion, the 3 groups were based on simple clinical data and seem to differ in some important baseline characteristics: the groups of PV JAK-2 negative and IE, however, seem still quite heterogeneous and deserve further and more accurate biological (exon 12 mutations) as well as clinical (venous blood p50 measurement) insights. The role of male gender and its predominance in unexplained erythrocitosis JAK-2 negative remain to be clarified. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    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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