Publications by authors named "Ilaria Nichele"

25 Publications

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Deep vein thrombosis (DVT) occurring shortly after the second dose of mRNA SARS-CoV-2 vaccine.

Intern Emerg Med 2021 04 9;16(3):803-804. Epub 2021 Mar 9.

Hematology Department, S. Bortolo Hospital, ULSS 8 Berica, Viale Rodolfi 37, 36100, Vicenza, Italy.

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http://dx.doi.org/10.1007/s11739-021-02685-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940863PMC
April 2021

Pain assessment and management in Italian Haemophilia Centres.

Blood Transfus 2020 Nov 27. Epub 2020 Nov 27.

A.O. SS. Antonio e Biagio, Alessandria, Italy.

Background: Although the widespread use of factor VIII/IX replacement therapy has significantly reduced the severity of arthropathy in persons with haemophilia (PWH), some develop degenerative joint changes, associated with significant pain. The aim of this survey was to investigate the management and perception of pain among Italian physicians who treat PWH.

Materials And Methods: Between September and October 2017, a questionnaire was distributed to 35 Italian haemophilia treatment centres (60 physicians).

Results: Fifty-three haemophilia specialists completed the survey. We found that there was good agreement (98.1%) on the need to investigate pain at each clinical visit, but there was heterogeneity in the opinions of haemophilia specialists with regards to the availability of validated guidelines (35.8%) and whether pain specialists should be a part of the comprehensive care team in daily clinical practice (58.5%). Haemophilia specialists also agreed pain should be evaluated using a rating scale validated in PWH (88.7%). Pain was mainly managed by the haemophilia specialists themselves, supported by a physiatrist and physiotherapist, while a pain specialist was only involved in 26.4% of cases. The combination of paracetamol with tramadol or codeine was the most common first-line treatment, while cyclo-oxygenase-2 inhibitors, non-steroidal anti-inflammatory drugs, and opioids were less commonly used.

Discussion: There are some unmet needs in Italy regarding pain management for PWH and the management of pain in these patients by haemophilia specialists. There is a lack of evidence-based guidelines for these specialists to use, as well as a reluctance to involve pain specialists. The lack of spontaneous reporting of pain by PWH, despite using pain relief, highlights the need for clinicians to actively ask patients about any pain they may be experiencing.
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http://dx.doi.org/10.2450/2020.0085-20DOI Listing
November 2020

The effect of management models on thromboembolic and bleeding rates in anticoagulated patients: an ecological study.

Intern Emerg Med 2019 11 15;14(8):1307-1315. Epub 2019 Jul 15.

Department of Oncology, Centre for Bleeding Disorders and Coagulation, Careggi University Hospital, 50134, Florence, Italy.

The primary study objective is to compare the outcomes of patients taking oral anticoagulant medications in two distinct populations treated according to different management models (comprehensive vs. usual care). (Design: regional prospective cohort study; setting: hospital admission data from two regions). Eligible partecipants were patients taking oral anticoagulant drugs (vitamin K antagonist or direct oral anticoagulants), residents in the Vicenza and Cremona districts from February 1st, 2016 to June 30th, 2017. Patients were identified by accessing the administrative databases of patient drug prescriptions. The primary study outcome was admission to the Emergency Department for stroke, systemic arterial embolism, recurrence of venous thromboembolism or major bleeding. The study evaluated outcomes in 14,226 patients taking oral anticoagulants, of whom 6725 being followed in Cremona with a comprehensive management model. There were 19 and 45 thromboembolic events over 6205 and 6530 patient-years in the Cremona and Vicenza cohort, respectively (IRR 0.44, 95% CI 0.24-0.77). The reduction of events in the Cremona cohort was almost entirely explained by a decrease of events in patients taking VKA (IRR 0.41, 95% CI 0.20-0.78) but not DOACs (IRR 1.08, 95% CI 0.25-5.24). The rate of major bleeding was non-significantly higher in Cremona than in Vicenza (IRI 1.32; 95% CI 0.74-2.40). Across the two cohorts, the risk of bleeding was lower in patients being treated with DOACs rather than warfarin (10/4574 vs. 42/8161 event/person-years, respectively, IRR 0.42 95% CI 0.19-0.86). We conclude that a comprehensive management model providing centralized dose prescription and follow-up may significantly reduce the rate of thromboembolic complications, without substantially increasing the number of bleeding complications. Patients treated with direct oral anticoagulants appear to have a rate of thromboembolic complications comparable to VKA patients under the best management model, with a reduction of major bleeding.
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http://dx.doi.org/10.1007/s11739-019-02148-7DOI Listing
November 2019

Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus.

Blood Transfus 2019 05 24;17(3):171-180. Epub 2018 Oct 24.

Alessandria.

Background: Management of venous thromboembolism (VTE) in patients with haematologic malignancies and thrombocytopenia is clinically challenging due to the related risks. No prospective studies or clinical trials have been carried out and, therefore, no solid evidence on this compelling issue is available.

Methods: Given this, an expert panel endorsed by the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on Thrombosis and Haemostasis was set up to produce a formal consensus, according to the RAND method, in order to issue clinical recommendations about the platelet (PLT) cut-off for safe administration of low molecular weight heparin (LMWH) in thrombocytopenic (PLT <100×10/L) adult patients with haematologic malignancies affected by acute (<1 month) or non-acute VTE.

Results: In acute VTE, the panel suggests safe anticoagulation with LMWH at therapeutic doses for PLT between ≥50<100×10/L and at 50% dose reduction for PLT ≥30<50×10/L. In acute VTE for PLT <30×10/L, the following interventions are recommended: positioning of an inferior vena cava (IVC) filter with prophylactic LMWH administration and platelet transfusion. In non-acute VTE, anticoagulation with LMWH at therapeutic doses for PLT between ≥50<100×10/L or over and at 50% dose reduction for PLT ≥30<50×10/L is considered appropriate. The discontinuation of full or reduced therapeutic dose of LMWH is recommended for PLT <30×10/L, both in acute and non-acute VTE.

Discussion: We suggest using dose-adjusted LMWH according to PLT to optimise anticoagulant treatment in patients at high bleeding risk.
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http://dx.doi.org/10.2450/2018.0143-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596377PMC
May 2019

Thrombotic and hemorrhagic complications in idiopathic erythrocytosis.

Am J Hematol 2017 11 17;92(11):E639-E641. Epub 2017 Aug 17.

Department of Medicine, DIMED- University of Padua, Padua, Italy.

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http://dx.doi.org/10.1002/ajh.24873DOI Listing
November 2017

Scoring Systems for Estimating the Risk of Recurrent Venous Thromboembolism.

Semin Thromb Hemost 2017 Jul 6;43(5):493-499. Epub 2017 Jun 6.

Hematology Department, S. Bortolo Hospital, Vicenza, Italy.

The risk of recurrence after suspension of anticoagulant treatment in patients with a first episode of unprovoked venous thromboembolism (VTE) is highly variable from patient to patient. Not all patients are candidates for life-long anticoagulant therapy, essentially because there remain concerns for such an option regarding hemorrhagic complications and clinical monitoring. Thus, the "treat all" approach may be inadequate for some patients at low risk of relapse. Proper assessment of the recurrence risk may be helpful to decide the optimal therapeutic strategy in such patients. In recent years, attempts have been made to develop and validate clinical prediction rules to estimate the absolute risk of VTE recurrence in individual patients. This article highlights the advantages and disadvantages of such options, presenting three different prediction rules that have been published so far.
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http://dx.doi.org/10.1055/s-0037-1602662DOI Listing
July 2017

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.

Am J Hematol 2017 Feb;92(2):187-195

CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.
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http://dx.doi.org/10.1002/ajh.24614DOI Listing
February 2017

Effectiveness of lenalidomide in a patient with refractory anemia with ring sideroblasts and thrombocytosis with JAK2 (V617F) mutation.

Am J Hematol 2015 Aug 28;90(8):E148-9. Epub 2015 May 28.

Department of Hematology, San Bortolo Hospital, Vicenza, Italy.

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http://dx.doi.org/10.1002/ajh.24049DOI Listing
August 2015

Analysis of 65 pregnancies in 34 women with five different forms of inherited platelet function disorders.

Br J Haematol 2015 Aug 21;170(4):559-63. Epub 2015 Apr 21.

Department of Internal Medicine, University of Pavia-IRCCS Policlinico San Matteo Foundation, Pavia, Italy.

This study evaluated 65 pregnancies in 34 women with five different inherited platelet function disorders. Gestation was similar to that of the general population. Severe bleeds requiring blood transfusions were observed in 50% of deliveries in Glanzmann thrombasthenia (GT), but not in the patients with delta storage pool disease, Hermansky-Pudlak syndrome, P2Y12 defect or defect of thromboxane A2 receptor. Of note, severe haemorrhage also occurred in women with GT who had received prophylactic platelet transfusions, suggesting that better preventive treatments are required. Diagnosis and degree of spontaneous bleeding tendency before pregnancy were reliable parameters to predict the delivery-related bleeding risk.
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http://dx.doi.org/10.1111/bjh.13458DOI Listing
August 2015

Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients.

Blood 2014 Nov 16;124(19):2930-6. Epub 2014 Sep 16.

Unità Operativa Oncoematologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy;

The clinical outcome, response to treatment, and occurrence of acute complications were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and correlated with serological characteristics and severity of anemia at onset. Patients had been followed up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly direct antiglobulin test negative). The latter 2 categories more frequently showed a severe onset (hemoglobin [Hb] levels ≤6 g/dL) along with reticulocytopenia. The majority of warm AIHA patients received first-line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants, and rituximab. The cumulative incidence of relapse was increased in more severe cases (hazard ratio 3.08; 95% confidence interval, 1.44-6.57 for Hb ≤6 g/dL; P < .001). Thrombotic events were associated with Hb levels ≤6 g/dL at onset, intravascular hemolysis, and previous splenectomy. Predictors of a fatal outcome were severe infections, particularly in splenectomized cases, acute renal failure, Evans syndrome, and multitreatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians.
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http://dx.doi.org/10.1182/blood-2014-06-583021DOI Listing
November 2014

Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia.

Haematologica 2014 Aug 24;99(8):1387-94. Epub 2014 Apr 24.

Division of Angiology and Haemostasis, Department of Medical Specialisations, Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L.
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http://dx.doi.org/10.3324/haematol.2014.105924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116839PMC
August 2014

Bendamustine in chronic lymphocytic leukemia: outcome according to different clinical and biological prognostic factors in the everyday clinical practice.

Am J Hematol 2013 Nov 9;88(11):955-60. Epub 2013 Sep 9.

Clinica Ematologica, DISM, Azienda Ospedaliero Universitaria S. M. Misericordia, Udine, Italy.

Bendamustine proved to be effective for the treatment of chronic lymphocytic leukemia (CLL). However, the relationship between its activity with clinico-biological prognosticators has been addressed only in few studies. We retrospectively evaluated the efficacy of bendamustine, in a real-life contest, on 142 patients, median age 70 years, median number of previous regimens 2 (0-8, 13% previously untreated). Bendamustine was administered for a median number of 4 cycles, in 84% of cases with rituximab. Overall (ORR) and complete response (CRR) rates were 68 and 16.5%, respectively. Multivariate analysis demonstrated a relationship between ORR and number of prior treatments (OR 0.25, 95% CI 0.08-0.71; P = 0.009), del(17p) (OR 0.10, 95% CI 0.03-0.32; P < 0.001) and concomitant rituximab (OR 4.37, 95% CI 1.12-17.04; P = 0.033). The estimated 1- and 2-years overall survival (OS) and progression free survival (PFS) rates were 76, 61, 51, and 26%, respectively. Previous sensitivity to fludarabine (HR 0.36, 95% CI 0.16-0.82), response to bendamustine (HR 0.21, 95% CI 0.10-0.45), and del(17p) (HR 2.18, 95% CI 1.002-4.74) had a prognostic significance in multivariate analysis for PFS, while the number of previous therapies (HR 3.48, 95% CI 1.29-9.38; P = 0.014), concomitant use of rituximab (HR 0.32, 95% CI 0.11-0.93) and response to bendamustine (HR 0.22, 95% CI 0.07-0.66) were significant for OS. Side effects included grade 3-4 neutropenia, infections, thrombocytopenia and anemia which occurred in 40, 14, 14, and 10% of patients, respectively. These results confirm the activity and safety of bendamustine and rituximab combination even in patients with unfavorable clinical and biological features excluding del(17p).
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http://dx.doi.org/10.1002/ajh.23546DOI Listing
November 2013

B-cell receptor configuration and mutational analysis of patients with chronic lymphocytic leukaemia and trisomy 12 reveal recurrent molecular abnormalities.

Hematol Oncol 2014 Mar 17;32(1):22-30. Epub 2013 Jul 17.

Department of Hematology and Cell Therapy, S. Bortolo Hospital, Vicenza, Italy.

Trisomy 12 (+12) is the third most frequent cytogenetic aberration in chronic lymphocytic leukaemia (CLL) retrievable both as the sole chromosomal abnormality or in association with additional alterations. NOTCH1 mutations are known to be more prevalent among +12 patients, whereas mutations of FBXW7, a gene involved in NOTCH1 degradation, that lead to the constitutional activation of NOTCH1 have not been investigated in this setting. We analyzed a unicentric cohort of 44 +12 patients with CLL for mutations of TP53, NOTCH1 and FBXW7 genes, and we correlated them with B-cell receptor (BCR) configurations. FBXW7, TP53 and NOTCH1 mutations were identified in 4.5%, 6.8% and 18.2% of patients, respectively. FBXW7 and NOTCH1 mutations appeared in a mutually exclusive fashion, suggesting that both aberrations might affect the same biological pathway. We found that 44.1% of +12 CLL patients had stereotyped B-cell receptors, which is significantly higher than that observed in patients with CLL and no +12 (27%, p = 0.01). Subsets #1, #8, #10, #28 and #59 were the most represented stereotyped patterns, and IGHV4-39*01 was the gene configuration most commonly used. There was a significantly higher risk for Richter's syndrome (RS) transformation in patients with NOTCH1 or FBXW7 mutations, with four of the seven (57%) patients developing RS and characterized at least by one of the two abnormalities. These observations suggest that, similarly to the aberrations of NOTCH1, FBXW7 gene mutations may also result in cell proliferation and evasion from apoptosis in patients with +12 CLL. Together with the extremely high frequency of stereotyped BCRs and RS transformation, these abnormalities appear to cluster in these CLL patients with additional chromosome 12, suggesting a connection with the prognosis of the disease.
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http://dx.doi.org/10.1002/hon.2086DOI Listing
March 2014

Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia.

Am J Hematol 2013 Apr 28;88(4):277-82. Epub 2013 Feb 28.

Department of Hematology S. Bortolo Hospital, Vicenza, Italy.

The immunoglobulin heavy chain variable (IGHV) gene mutational status represents a major prognostic marker in chronic lymphocytic leukemia (CLL). Usually, the prognostic implications of IGHV gene analysis can be reliably ascertained but, occasionally, double productive rearrangements have been detected. Clinical presentation and biological features of such cases are unknown. Sixty patients with morphologically and phenotypically monoclonal CLL but double productive IGHV rearrangements were retrospectively identified by mRNA analysis from three Hematology Institutions. Clinical and biological features and survival of these 60 patients were compared with a control group of patients with CLL and single IGHV rearrangement. A prospective registry was used to assess the epidemiology of double productive IGHV among incidental patients with CLL. Using standard criteria to define IGHV-mutated (M) or unmutated (U) cases, 39 of the 60 patients (65%) with double productive IGHV rearrangement had concordant status (23 MM, 16 UU), while 21 (35%) had discordant IGHV status. As compared with M patients, the MM ones had lower CD38 expression, more favorable cytogenetics and more indolent clinical behavior. Cases with UU had similar characteristics of U patients. Discordant cases presented with adverse prognostic features and had an aggressive clinical behavior requiring early treatment, similar to U patients. The prevalence of double IGHV was 3.1%. Patients with CLL with double concordant mutational status (MM or UU) have a clinical course similar to that of the corresponding single IGHV status, while those exhibiting discordant status represent a high risk population. This may help correct stratification within clinical trials.
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http://dx.doi.org/10.1002/ajh.23396DOI Listing
April 2013

VR09 cell line: an EBV-positive lymphoblastoid cell line with in vivo characteristics of diffuse large B cell lymphoma of activated B-cell type.

PLoS One 2012 21;7(12):e52811. Epub 2012 Dec 21.

Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.

Background: small B-cell neoplasms can show plasmacytic differentiation and may potentially progress to aggressive lymphoma (DLBCL). Epstein-Barr virus (EBV) infection may cause the transformation of malignant cells in vitro.

Design And Method: we established VR09 cell line with plasmacytic differentiation, obtained from a case of atypical, non-CLL B-cell chronic lymphoproliferative disease with plasmacytic features. We used flow cytometry, immunohistochemistry, polymerase chain reaction, cytogenetic analysis and florescence in situ hybridization in the attempt at thoroughly characterizing the cell line. We showed VR09 tumorigenic potential in vivo, leading to the development of activated DLBCL with plasmacytic features.

Results: VR09 cells displayed plasmacytic appearance and grew as spherical tumors when inoculated subcutaneously into immunodeficient Rag2(-/-) γ-chain(-/-) mice. VR09 cell line and tumors displayed the phenotype of activated stage of B cell maturation, with secretory differentiation (CD19+ CD20+ CD79a+ CD79b+/- CD138+ cyclin D1- Ki67 80% IgM+ IgD+ MUM1+ MNDA+ CD10- CD22+ CD23+ CD43+ K+, λ- Bcl2+ Bcl6-) and they presented episomal EBV genome, chromosome 12 trisomy, lack of c-MYC rearrangement and Myd88 gene mutation, presence of somatic hypermutation in the VH region, and wild-type p53.

Conclusion: This new EBV-positive cell line may be useful to further characterize in vivo activated DLBCL with plasmacytic features.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052811PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528718PMC
June 2013

Association between B-cell receptor responsiveness and disease progression in B-cell chronic lymphocytic leukemia: results from single cell network profiling studies.

Haematologica 2013 Apr 9;98(4):626-34. Epub 2012 Nov 9.

Nodality Inc., South San Francisco, CA, USA.

While many prognostic markers in B-cell chronic lymphocytic leukemia provide insight into the biology of the disease, few have been demonstrated to be useful in the daily management of patients. B-cell receptor signaling is a driving event in the progression of B-cell chronic lymphocytic leukemia and markers of B-cell receptor responsiveness have been shown to be of prognostic value. Single cell network profiling, a multiparametric flow cytometry-based assay, allows functional signaling analysis at the level of the single cell. B-cell receptor signaling proteins (i.e. p-SYK, p-NF-κB p65, p-ERK, p-p38, p-JNK) were functionally characterized by single cell network profiling in samples from patients with B-cell chronic lymphocytic leukemia in an exploratory study (n=27) after stimulation with anti-IgM. Significant associations of single cell network profiling data with clinical outcome (i.e. time to first treatment), as assessed by Cox regression models, were then confirmed in patients' samples in two other sequential independent studies, i.e. test study 1 (n=30), and test study 2 (n=37). In the exploratory study, higher responsiveness of the B-cell receptor signaling proteins to anti-IgM was associated with poor clinical outcomes. Patients' clustering based on signaling response was at least as powerful in discriminating different disease courses as traditional prognostic markers. In an unselected subgroup of patients with Binet stage A disease (n=21), increased anti-IgM-modulated p-ERK signaling was shown to be a significant, independent predictor of shorter time to first treatment. This result was independently confirmed in two test cohorts from distinct populations of patients. In conclusion, these findings support the utility of the single cell network profiling assay in elucidating signaling perturbations with the potential for the development of a clinically useful prognostic test in patients with early stage B-cell chronic lymphocytic leukemia. These data support the clinical relevance of B-cell receptor signaling in B-cell chronic lymphocytic leukemia, and suggest a key role of ERK activation in the physiopathology of this leukemia.
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http://dx.doi.org/10.3324/haematol.2012.071910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685273PMC
April 2013

Predictors of anxiety and depression in hematopoietic stem cell transplant patients during protective isolation.

Psychooncology 2013 Aug 7;22(8):1790-7. Epub 2012 Nov 7.

Section of Hematology and Bone Marrow Transplant Unit, Department of Medicine, University of Verona, Verona, Italy.

Objective: To examine in a sample of hematopoietic stem cell transplant patients assessed throughout protective isolation (i) levels of anxiety and depression and (ii) pre-isolation factors (socio-demographics, biomedical variables and personality traits), which might predict higher levels of anxiety and depression during isolation.

Methods: The study used a longitudinal prospective design. Anxiety and depression were assessed in 107 participants by the State-Trait Anxiety Inventory and Self-rating Depression Scale at admission and weekly at fixed time points throughout isolation. Among pre-isolation factors, patients' psychological status was evaluated by the Cognitive Behavioral Assessment (2.0). Predictors were explored by random-effects models.

Results: One-tenth of the patients suffered from clinically significant anxiety and depressive symptoms at admission. Although the percentage of depressed patients increased more than twofold after 2 weeks of isolation, that of anxious patients did not significantly change over time. Female gender, higher anxiety and obsessive-compulsive symptoms, intratensive personality traits and lower performance status predicted higher depression during isolation.

Conclusions: Anxiety and depression represent a relevant problem for hematopoietic stem cell transplant patients during isolation. Early detection of predictors, such as anxiety levels, obsessive-compulsive symptoms and performance status, could help prevent depression via targeted psychological intervention.
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http://dx.doi.org/10.1002/pon.3215DOI Listing
August 2013

B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia.

Am J Hematol 2013 Jan 31;88(1):32-6. Epub 2012 Oct 31.

Department of Clinical Sciences and Community Health, University of Milan, Italy.

The development of autoimmune hemolytic anemia (AIHA) in patients with chronic lymphocytic leukemia (CLL) is associated with specific biological features. The occurrence of AIHA was hereby investigated in a retrospective series of 585 CLL patients with available immunoglobulin heavy chain variable (IGHV) gene status. AIHA occurred in 73 patients and was significantly associated with an IGHV unmutated (UM) status (P < 0.0001) and unfavorable [del(17)(p13) and del(11)(q23)] cytogenetic lesions (P < 0.0001). Stereotyped HCDR3 sequences were identified in 29.6% of cases and were similarly represented among patients developing or not AIHA; notably, subset #3 was associated with a significantly higher risk of AIHA than the other patients (P = 0.004). Multivariate analysis showed that UM IGHV, del(17)(p13) and del(11)(q23), but not stereotyped subset #3, were the strongest independent variables associated with AIHA. Based on these findings, we generated a biological risk score for AIHA development according to the presence of none (low risk), one (intermediated risk), or two (high risk) of the independent risk factors. Overall, our data indicate that UM IGHV status and/or unfavorable cytogenetic lesions are associated with the risk of developing secondary AIHA in CLL patients and suggest a possible role of specific stereotyped B-cell receptor subsets in a proportion of cases.
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http://dx.doi.org/10.1002/ajh.23342DOI Listing
January 2013

Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome.

Blood 2012 Mar 13;119(10):2239-41. Epub 2012 Jan 13.

Ospedali Riuniti di Bergamo, Italy.

We examined the prevalence and prognostic relevance of bone marrow reticulin fibrosis in 526 patients with World Health Organization-defined polycythemia vera evaluated at the time of initial diagnosis. Seventy-four patients (14%) displayed mostly grade 1 reticulin fibrosis, with only 2 cases showing higher-grade fibrosis. Presenting clinical and laboratory characteristics, including JAK2V617F allele burden, between patients with and without fibrosis were similar for the most part, with the exception of a higher prevalence of palpable splenomegaly in patients with fibrosis (P < .01). Patients with fibrosis were less prone to experience thrombosis during their clinical course (1.1 vs 2.7 per 100 patient-years; P = .03) and more prone to develop post-polycythemia vera myelofibrosis (2.2 vs 0.8 per 100 patient-years; P = .01). There was no significant difference between the 2 groups in terms of overall or leukemia-free survival. The present study clarifies the incidence, degree, and prognostic relevance of bone marrow fibrosis obtained at time of initial diagnosis of polycythemia vera.
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http://dx.doi.org/10.1182/blood-2011-11-393819DOI Listing
March 2012

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters.

Blood 2012 Mar 13;119(10):2310-3. Epub 2012 Jan 13.

Section of Hematology, Azienda Ospedaliero-Universitaria, Arcispedale S. Anna, University of Ferrara, Italy.

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features.
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http://dx.doi.org/10.1182/blood-2011-11-395269DOI Listing
March 2012

The coexistence of chronic lymphocytic leukemia and myeloproliperative neoplasms: a retrospective multicentric GIMEMA experience.

Am J Hematol 2011 Dec 22;86(12):1007-12. Epub 2011 Sep 22.

Hematology Institute, Catholic University, Largo A. Gemelli 8, Rome, Italy.

Although the coexistence of chronic lymphocytic leukemia (CLL) and myeloproliferative neoplasms (MPN) has been sporadically reported in the literature, no systematic studies on this disease association are available. We retrospectively analyzed 46 patients affected by CLL/MPN referred by 15 Italian GIMEMA centers. The aim of this retrospective multicenter study was to define the following: clinico-biological characteristics, possible familiarity, clinical course of both diseases, and influence of MPN chemotherapy on the course of CLL. Among 46 patients, 30 patients were males, 16 patients were females; median age was 71 years. Only one case had familiar CLL. Myeloproliferative disorders consisted of essential thrombocytemia in 18 cases, polycythemia vera in 10 cases, chronic myeloid leukemia in 9 cases, primary myelofibrosis in 6 cases, and MPN/myelodysplastic syndrome in 3 cases. The lymphoproliferative disorder was diagnosed as monoclonal B-cell lymphocytosis in 8 patients and as Binet Stage A CLL in 38 patients. After a median follow-up of 49 months, 9 patients experienced progressive CLL and only 6 patients required treatment after a median of 57.5 months. The biological profile confirmed a subset of low-risk CLL. Twenty patients received chemotherapy for MPN without influence on the course of CLL: lymphocyte counts remained unchanged after 3, 6, and 12 months of treatment. This series is the largest so far reported in literature. The diagnosis of concomitant CLL/MPN is a rare event and lymphoproliferative disorders present a clinical indolent course with a low-risk biological profile. MPN therapy does not interfere with the prognosis of patients with CLL.
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http://dx.doi.org/10.1002/ajh.22171DOI Listing
December 2011

A proliferation-inducing ligand (APRIL) serum levels predict time to first treatment in patients affected by B-cell chronic lymphocytic leukemia.

Eur J Haematol 2011 Sep 26;87(3):228-34. Epub 2011 Jul 26.

Section of Hematology, Department of Medicine, University of Verona, Piazzale L A Scuro 10, Verona, Italy.

Purpose: A proliferation-inducing ligand (APRIL), a tumor necrosis factor superfamily member involved in B-lymphocytes differentiation and survival, plays a role in protecting B-Cell Chronic lymphocytic leukemia (B-CLL) cells from apoptosis. Having observed that APRIL serum (sAPRIL) levels were higher in B-CLL patients with CLL at diagnosis as compared to healthy donors (14.61±32.65 vs. 4.19±3.42 ng/mL; P<0.001), we tested the correlation existing in these patients between sAPRIL, clinical-biological parameters and disease progression.

Experimental Design: sAPRIL levels were measured by ELISA in 130 patients with B-CLL at diagnosis and in 25 healthy donors.

Results: sAPRIL levels did not correlate with gender, age, clinical stage, blood cell counts, β2-microglobulin (β2M) levels, ZAP-70 and CD38 expression. Using median sAPRIL natural logarithm (ln) as cutoff, we distinguished two groups of patients (APRIL(LOW) and APRIL(HIGH) ) who were comparable with regard to clinical-biological parameters and overall survival, but different with regard to time to the first treatment (TTFT; P=0.035). According to univariate analysis, high lymphocyte count, high β2M, Binet stage B-C, ZAP-70 expression and ln(sAPRIL) above median were associated with earlier TTFT. Advanced clinical stage, high β2M, ZAP-70 expression and ln(sAPRIL) above median remained independently predictive of shorter TTFT at multivariate analysis. Moreover, sAPRIL increased its prognostic significance when patients were stratified according to independent favorable clinical-biological characteristics (low β2M, stage A and lack of ZAP-70 expression).

Conclusions: sAPRIL is a novel indicator of shorter TTFT in B-CLL and a predictor of progression especially in patients otherwise considered at low risk according to validated prognostic factors.
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http://dx.doi.org/10.1111/j.1600-0609.2011.01650.xDOI Listing
September 2011

Thrombocytopenias: a clinical point of view.

Blood Transfus 2009 Apr;7(2):75-85

Dipartimento di Medicina Clinica e Sperimentale, Sezione di Ematologia, Università di Verona, Verona, Italy.

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http://dx.doi.org/10.2450/2008.0012-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689060PMC
April 2009