Valentina Carrai

University of Florence, Florens, Tuscany, Italy

Are you Valentina Carrai?

Claim your profile

Publications (26)110.25 Total impact

  • Source
    Rheumatology (Oxford, England) 06/2015; 54(9). DOI:10.1093/rheumatology/kev242 · 4.48 Impact Factor
  • Alberto Bosi · Valentina Carrai
    11/2014; 3(2):55. DOI:10.4081/dcth.2014.69
  • S Baldini · V Carrai · B Puccini · L Rigacci · R Alterini · A Bosi
    Transfusion Medicine 04/2014; 24(2):125-6. DOI:10.1111/tme.12106 · 1.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the gene calreticulin (CALR) occur in the majority of JAK2 and MPL unmutated patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF); identifying CALR mutations contributes to the diagnostic pathway of ET and PMF. CALR mutations are heterogeneous spanning over the exon 9, but all result in a novel common protein C-terminus. We developed a polyclonal antibody against a 17-aminoacid peptide derived from mutated calreticulin that was used for immunostaining of bone marrow biopsies. We show that this antibody specifically recognized patients harboring different types of CALR mutation with no staining in healthy controls and JAK2 or MPL mutated ET and PMF. The labelling was mostly localized in megakaryocytes while myeloid and erythroid cells showed faint staining, suggesting a preferential expression of calreticulin in megakaryocytes. Megakaryocytic-restricted expression of calreticulin was also demonstrated using an antibody against wildtype calreticulin and by measuring the levels of calreticulin RNA by gene expression analysis. Immunostaining using antibody specific for mutated calreticulin may become a rapid, simple and cost-effective method for identifying CALR mutated patients complementing molecular analysis; furthermore, labelling pattern supports the preferential expansion of megakaryocytic cell lineage as result of CALR mutation in an immature hematopoietic stem cell.Leukemia accepted article preview online, 12 March 2014; doi:10.1038/leu.2014.100.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2014; 28(9). DOI:10.1038/leu.2014.100 · 10.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined the baseline features and clinical outcomes of 140 patients presenting with JAK2V617F positivity and a bone marrow morphology conforming with WHO criteria of polycythemia vera (PV), but a hemoglobin level of <18.5 g/dL in males (range 16.0-18.4) and <16.5 g/dL in females (range 15.0-16.4). This cohort operationally referred to as masked PV (mPV) was compared with 257 patients with overt PV and displayed male predominance, a more frequent history of arterial thrombosis and thrombocytosis. Incidence of thrombosis was similar between the two groups but mPV displayed significantly higher rates of progression to myelofibrosis and acute leukemia and inferior survival. In multivariable analysis mPV diagnosis was an independent predictor of poor survival along with age >65 years and leukocyte count >10x10(9) /L. Our data suggest that mPV is a heterogeneous myeloproliferative neoplasia and not necessarily an early/ pre-polycythemic form of classical PV that at onset in a small fraction of patients clinically may mimick essential thrombocythemia. On the other hand, the majority mPV may have a longer prodrome of undiagnosed PV or a disease biology akin to primary myelofibrosis-post PV myelofibrosis that could explain the worsening of outcome in comparison to overt /classical manifestations.
    American Journal of Hematology 01/2014; 89(1). DOI:10.1002/ajh.23585 · 3.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a unique disorder caused by a PIG-A gene mutation in a stem cell clone. Its clinical picture can sometimes make challenging the distinction from other disorders, and especially from myelodysplastic syndromes (MDS), since both diseases correlate with cytopenias and morphological abnormalities of bone marrow (BM) cells. Recently, flow cytometry (FC) has been proposed to integrate the morphologic assessment of BM dysplasia, and thus to improve the diagnostics of MDS. Methods: In the present study, we have analyzed systematically FC data resulting from the study of BM cells from patients with PNH and MDS. Results: Our data demonstrated abnormalities in PNH beyond the deficiency of glycosylphosphatidylinositol-linked proteins and the application of a systematic approach allowed us to separate effectively MDS and PNH in a cluster analysis and to highlight disease-specific abnormalities. Indeed, the parallel evaluation of some key parameters, i.e. patterns of expression of CD45 and CD10, provided information with practical diagnostic usefulness in the distinction between PNH and MDS. Moreover, the hypo-expression of CD36 that we observed on monocytes might be related to the thrombotic tendency in PNH. Conclusions: We investigated systematically the phenotypic profile of BM cells from patients with PNH; our data provide useful antigenic patterns to solve between PNH and MDS, sometimes morphologically overlapping. Moreover, some PNH-related phenotypic changes might be involved in the physiopathology of the disease and further studies addressing this issue are warranted.
    Cytometry Part B Clinical Cytometry 03/2013; 84B(2). DOI:10.1002/cyto.b.21064 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Recently autologous haematopoietic stem cell transplantation (AHSCT) has been introduced for the treatment of severe forms of multiple sclerosis (MS). As little data are available on bone marrow (BM) of MS patients undergoing AHSCT, we investigated the morphological and phenotypic characteristics of MS BM. Methods: BM biopsies of 14 MS patients screened for AHSCT and 10 control patients were evaluated to assess cellularity, morphology, immunological profile and bone marrow microenvironment. Immunohistochemistry analysis was performed to evaluate the expression of CD3, CD4, CD8, CD20, CD68, CD45, MMP-9. Results: 8 out of 14 MS (57%) patients showed a reduction of age-related bone marrow cellularity, possibly due to previous immunosuppressive therapies. There were no differences in the T CD3+ lymphocyte expression rate amongst MS and the control patients, the CD4/CD8 ratio (2:1) was maintained as was the rate of B lymphocytes. We found an increased, although not significant, MMP-9 expression (9.2%) in the bone marrow of MS patients, when compared to the control patients (6.3%). Conclusion: The BM of MS patients showed a reduced cellularity and CD45+ cells content in comparison to the controls. A slightly increased expression of MMP-9 was also shown, possibly confirming an involvement of this compartment in the pathogenesis of the disease.
    Clinical neurology and neurosurgery 12/2012; 115(7). DOI:10.1016/j.clineuro.2012.10.032 · 1.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Immune thrombocytopenia (ITP) is an autoimmune disorder that occasionally arises with neoplasms. Although often sensitive to first-line treatment, a refractory thrombocytopenia may lead to a difficult management of the patient. A patient with primary ITP who successfully underwent surgery and chemotherapy with immunoglobulins and dexamethasone for ovarian cancer has recently been reported. We report on a 71-year-old woman who developed refractory secondary ITP concomitant with an advanced serous ovarian carcinoma. The ITP responded only to the thrombopoietin receptor agonist romiplostim with an uncommon threshold effect, enabling both palliative surgery and histological diagnosis. Although thrombopoietin receptor agonists might be useful in some circumstances, their safety and efficacy for cancer patients must still be determined. Well-designed clinical trials are urgently needed to resolve this issue.
    10/2012; 1(4):239-242. DOI:10.1007/s13691-012-0049-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diagnosis of essential thrombocythemia (ET) has been updated in the last World Health Organization (WHO) classification. We developed a prognostic model to predict survival at diagnosis, named IPSET (International Prognostic Score for ET), studying patients with WHO-defined ET. Age 60 years or older, leukocyte count ≥ 11 × 10(9)/L, and prior thrombosis significantly affected survival, by multivariable Cox regression. On the basis of the hazard ratio, we assigned 2 points to age and 1 each to leukocyte count and thrombosis. So, the IPSET model allocated 867 patients into 3 risk categories with significantly different survival: low (sum of points = 0; median survival not reached), intermediate (sum = 1-2; median survival 24.5 years), and high (sum = 3-4, median survival 13.8 years). The IPSET model was further validated in 2 independent cohorts including 132 WHO-defined ET and 234 Polycythemia Vera Study Group-defined ET patients. The IPSET model was able to predict the occurrence of thrombosis, and not to predict post-ET myelofibrosis. In conclusion, IPSET, based on age ≥ 60 years, leukocyte count ≥ 11 × 10(9)/L, and history of thrombosis allows prognostic assessment of WHO-defined ET and the validation process makes IPSET applicable in all patients phenotypically appearing as ET.
    Blood 06/2012; 120(6):1197-201. DOI:10.1182/blood-2012-01-403279 · 10.45 Impact Factor
  • Platelets 05/2012; 24(3). DOI:10.3109/09537104.2012.686074 · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dysfunctional angiogenesis is a pathogenetic marker of SSc. Circulating levels of endothelial progenitor cells are reduced, and mesenchymal stromal cells show a reduced differentiation into endothelial cells and capacity to form capillaries. This suggests that pathophysiologically relevant changes may already exist in SSc bone marrow (BM) stromal cells that may affect downstream angiogenesis. The aim of this study is to evaluate, in SSc BM, angiogenesis, cellular immune system and fibrosis. Eight SSc patients affected by a severe dcSSc and screened for autologous haematopoietic stem cells transplantation (HSCT) underwent a BM biopsy. BM biopsies were compared with six healthy controls. To evaluate angiogenesis and cellular immunity, the following antibodies were used: vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/flk-1), MMP-9 and CD34. To evaluate fibrosis, silver impregnation for reticulum was used. The number of vessels, the mean area of vascularization, the perimeter and microvessel density (MVD) were measured with a multiparametric computerized imaging analysis. A significant reduction in BM vascularity was found, while VEGF expression was much higher in SSc BM samples. Two patients had a Grade 2, whereas another two had a Grade 1 fibrosis. In SSc, BM is characterized by a reduction of microvascular density and number of vessels and a significant increase of VEGF. This indicates that BM may be involved in the process of loss of angiogenesis, despite the presence of high local and systemic levels of VEGF.
    Rheumatology (Oxford, England) 01/2012; 51(6):1042-8. DOI:10.1093/rheumatology/ker447 · 4.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with chronic immune thrombocytopenia treated with romiplostim may benefit from a higher starting dose when a rapid increase in count is needed, but it could be avoided in those with a prompt response to the standard dosage. We hypothesized that a platelet count ≥ 20 × 10(9)/l at baseline could distinguish subjects with such response from those with a delayed one during the early phase of treatment. Our work is a retrospective and single-institution analysis comparing the median platelet count, the median weekly dosage of romiplostim and the median number of weekly platelet counts < 50 × 10(9)/l between patients with a baseline ≥ 20 × 10(9)/l platelets (n=10, 2 splenectomized) and those with a lower one (n=8, 3 splenectomized) during the first month of treatment with romiplostim. The results show a higher median platelet count (79,5 vs 40,5 × 10(9)/l, p=0,002) and a lower median dose of romiplostim (1 vs 2 mcg/kg/week, p=0,01) in subjects with a baseline ≥ 20 × 10(9)/l platelets, who also had a trend of less weekly counts < 50 × 10(9)/l platelets (1 vs 2, p=0,054). These data suggest that patients with ≥ 20 × 10(9)/l platelets at baseline may achieve a prompt response with the standard dose of romiplostim, but further and larger data are needed in order to assess whether it can be considered in clinical practice.
    Mediterranean Journal of Hematology and Infectious Diseases 01/2012; 4(1):e2012044. DOI:10.4084/MJHID.2012.044
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The WHO diagnostic criteria underscore the role of bone marrow (BM) morphology in distinguishing essential thrombocythemia (ET) from early/prefibrotic primary myelofibrosis (PMF). This study examined the clinical relevance of such a distinction. Representatives from seven international centers of excellence for myeloproliferative neoplasms convened to create a clinicopathologic database of patients previously diagnosed as having ET (N = 1,104). Study eligibility criteria included availability of treatment-naive BM specimens obtained within 1 year of diagnosis. All bone marrows subsequently underwent a central re-review. Diagnosis was confirmed as ET in 891 patients (81%) and was revised to early/prefibrotic PMF in 180 (16%); 33 patients were not evaluable. In early/prefibrotic PMF compared with ET, the 10-year survival rates (76% and 89%, respectively) and 15-year survival rates (59% and 80%, respectively), leukemic transformation rates at 10 years (5.8% and 0.7%, respectively) and 15 years (11.7% and 2.1%, respectively), and rates of progression to overt myelofibrosis at 10 years (12.3% and 0.8%, respectively) and 15 years (16.9% and 9.3%) were significantly worse. The respective death, leukemia, and overt myelofibrosis incidence rates per 100 patient-years for early/prefibrotic PMF compared with ET were 2.7% and 1.3% (relative risk [RR], 2.1; P < .001), 0.6% and 0.1% (RR, 5.2; P = .001), and 1% and 0.5% (RR, 2.0; P = .04). Multivariable analysis confirmed these findings and also identified age older than 60 years (hazard ratio [HR], 6.7), leukocyte count greater than 11 × 10(9)/L (HR, 2.01), anemia (HR, 2.95), and thrombosis history (HR, 2.81) as additional risk factors for survival. Thrombosis and JAK2V617F incidence rates were similar between the two groups. Survival in ET was similar to the sex- and age-standardized European population. This study validates the clinical relevance of strict adherence to WHO criteria in the diagnosis of ET and provides important information on survival, disease complication rates, and prognostic factors in strictly WHO-defined ET and early/prefibrotic PMF.
    Journal of Clinical Oncology 08/2011; 29(23):3179-84. DOI:10.1200/JCO.2010.34.5298 · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the efficacy of a new agent, palonosetron, in Hodgkin Lymphoma patients treated with ABVD regimen. Complete response during the overall phase of the first ABVD cycle, was the primary endpoint. Secondary end points were: emesis-free patients and use of rescue medication during the acute and overall phases. From January 2008 to February 2009 36 patients were enrolled. The primary endpoint (CR 0-120 h) was achieved by 55.6% patients. In conclusion our study demonstrated that a single dose of palonosetron plus a single dose of dexamethasone was effective in preventing CINV in patients treated with ABVD regimen.
    Leukemia research 07/2011; 36(2):182-5. DOI:10.1016/j.leukres.2011.06.025 · 2.35 Impact Factor
  • Leukemia Research 05/2011; 35. DOI:10.1016/S0145-2126(11)70319-8 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.
    Blood 08/2008; 112(3):844-7. DOI:10.1182/blood-2008-01-135897 · 10.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy and safety of the combination of non-pegylated liposome-encapsulated doxorubicin (Myocet(R)) with cyclophosphamide, vincristine, prednisone and rituximab (R-COMP) in patients with aggressive non-Hodgkin's B-cell lymphomas. Twenty-one patients were selected for the presence of negative concurrent clinical features such as cardiac comorbidity and/or previous treatment with anthracycline-based regimens. Liposome-encapsulated doxorubicin at a dose of 50 mg/m(2) was administered in association with cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), prednisone (40 mg/m(2)) and rituximab (375 mg/m(2)) every 21 days for four to six cycles unless progression or unacceptable toxicity occurred. A complete response (CR) was obtained in 16/21 patients (76%), three patients achieved a partial response (14%), with an overall response rate of 90%. Two patients (10%) did not respond to therapy. After a median follow-up of 13 months (range 2-36 months), 2/16 CR patients relapsed, with a disease-free survival (DFS) of 78%. The replacement of doxorubicin with its non-pegylated liposomal pharmaceutical analogue was well tolerated and highly effective in inducing remission in this group of patients at high risk for cardiac toxicity or previously treated with anthracyclines. Its high tolerability and low incidence of cardiac events (only one patient) warrants further studies to confirm the clinical benefits of liposomal doxorubicin in this subset of patients.
    Hematological Oncology 12/2007; 25(4):198-203. DOI:10.1002/hon.827 · 3.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ocular adnexal lymphomas (OALs) are typically low-grade lymphomas and are largely represented by marginal-zone lymphomas (EMZL). Radiotherapy is the treatment of choice but is frequently associated to local complications. We investigated the association of chlorambucil and rituximab as first-line treatment for primary OALs. Nine consecutive, newly diagnosed OALs patients (eight with a EMZL, one with a follicular lymphoma) with a median age of 78 years were treated with this combination. Eight patients were in stage I-A, and one was in stage IV-A; all patients had low LDH values. Eight patients (89%) obtained a complete remission and one a partial response. All completed the treatment without significant toxicities. After a median follow up of 25 months, all patients are alive; no progressions or late toxicities were observed. Rituximab in combination with chlorambucil proved to be a feasible option as first-line treatment for OALs because of its feasibility and the absence of toxicity and local sequelae.
    Annals of Hematology 09/2007; 86(8):565-8. DOI:10.1007/s00277-007-0301-y · 2.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aggressive non-Hodgkin's lymphomas (NHL) require intensive therapies which seemed impracticable in elderly patients. Dose reduction and therapy attenuation reduced treatment-related toxicity, but also decreased therapeutic efficacy. In elderly patients too, the achievement of complete remission is the most important prognostic factor affecting outcome. Therefore, we have treated elderly patients with a dose-intensified protocol. Aim of the study was to verify the feasibility of this scheme in a subset of patients with high-risk aggressive lymphomas. Between June 2002 and June 2004, 26 patients over the age of 60 years with a diagnosis of aggressive NHL and an intermediate-high or high International Prognostic Index were treated with biweekly CHOP plus rituximab with the support of granulocyte colony-stimulating factors (G-CSF). Seventeen patients (65%) regularly kept the interval between cycles. Haematological and extrahaematological toxicities were moderate in all the patients. Twenty (77%) patients achieved complete remissions, 6 (23%) partial remissions with an overall response rate of 100%. After a median follow-up of 23 months, the overall survival was 79%; after a median follow-up of 17 months, the disease-free survival was 70%. These results confirm that a dose-dense CHOP programme can be administered safely and effectively in a subset of elderly patients with high-risk aggressive NHL. The addition of rituximab could increase the response rate without adding toxicity.
    Acta Haematologica 02/2006; 115(1-2):22-7. DOI:10.1159/000089461 · 1.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In patients with Hodgkin's lymphoma (HL) at the end of first line therapy an accurate imaging technique with high prognostic value is needed to assess response to treatment and predict those patients who will suffer disease relapse. This technique and its results permit the quick initiation of a second line therapy in patients suffering from a progressive disease or those unresponsive to treatment avoid over-treatment of patients in complete remission or those having a non-active residual disease. We included a (18)FDG-positron emission tomography (PET) scan to the diagnostic set-up to investigate 28 patients following the end of their treatment. Fifteen patients out of the 28 (54%) had positive CT scans while 13 (46%) had negative ones. Eleven patients out of the 15 CT positive (73%) had negative PET scans and no relapse. The remaining four patients (27%) had positive PET scans with only one relapse (25%). With respect to the 13 patients who had negative CT scans, 9 patients (69%) had negative PET scans and no relapse. The remaining 4 patients (31%) had positive PET scans with 3 relapse cases (75%). In our final assessment after a median follow-up period of 45 months, starting from PET execution to the last follow-up, overall sensitivity of the CT and the PET were 25 and 100% respectively, specificity 42 and 83% respectively, positive predictive value (PPV) 7 and 50% respectively, negative predictive value (NPV) 77 and 100% respectively, and accuracy 39 and 86% respectively. In our experience, FDG-PET performed in patients after induction therapy appears to offer important additional information: FDG-PET results are predictors of prognosis giving 100% DFS in PET negative patients and 54% DSF in PET positive patients.
    Oncology Reports 12/2005; 14(5):1209-14. DOI:10.3892/or.14.5.1209 · 2.30 Impact Factor

Publication Stats

363 Citations
110.25 Total Impact Points


  • 1999–2014
    • University of Florence
      • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      Florens, Tuscany, Italy
  • 2011
    • University of Cologne
      • Institute of Pathology
      Köln, North Rhine-Westphalia, Germany
  • 2007–2011
    • Azienda Ospedaliero Universitaria Careggi
      • Department of Hematology
      Firenzuola, Tuscany, Italy