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Laura Vanelli

Publications and source records attributed to Laura Vanelli.

6 recordsLinked to original sources
PubMed2005

Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders.

We studied the relationship between granulocyte JAK2 (V617F) mutation status, circulating CD34(+) cells, and granulocyte activation in myeloproliferative disorders. Quantitative allele-specific polymerase chain reaction (PCR) showed significant differences between various disorders with respect to either the proportion of positive patients (53%-100%) or that of mutant alleles, which overall ranged from 1% to 100%. In polycythemia vera, JAK2 (V617F) was detected in 23 of 25 subjects at diagnosis and in 16 of 16 patients whose disease had evolved into myelofibrosis; median percentages of mutant alleles in these subgroups were significantly different (32% versus 95%, P < .001). Circulating CD34(+) cell counts were variably elevated and associated with disease category and JAK2 (V617F) mutation status. Most patients had granulocyte activation patterns similar to those induced by administration of granulocyte colony-stimulating factor. A JAK2 (V617F) gene dosage effect on both CD34(+) cell counts and granulocyte activation was clearly demonstrated in polycythemia vera, where abnormal patterns were mainly found in patients carrying more than 50% mutant alleles. These observations suggest that JAK2 (V617F) may constitutively activate granulocytes and by this means mobilize CD34(+) cells. This exemplifies a novel paradigm in which a somatic gain-of-function mutation is initially responsible for clonal expansion of hematopoietic cells and later for their abnormal trafficking via an activated cell progeny.

Adolescent↗
PubMed2004

Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia: correlations with clinical and transplant characteristics.

We have analyzed the kinetics of reconstitution of circulating dendritic cell (DC) subsets (myeloid-DC1 and lymphoid-DC2) in 19 patients affected by acute leukemia undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). We have found that pretransplant DC1 and DC2 were lower in leukemic patients than in healthy subjects (P = 0.003 and P = 0.004, respectively) and that the number of DC2 (but not DC1) infused with the graft was higher in patients receiving peripheral blood stem cells (PBSC) (P = 0.03). Patients recovered to the pretransplant DC1 and DC2 levels within day +60; however, a normal DC1 number was reached on day +365, while DC2 remained lower than in controls up to 1 yr after transplant. DC1 reconstitution did not differ significantly between patients receiving bone marrow stem cells (BMSC) or PBSC, while patients receiving PBSC presented increased levels of DC2 on day +30 (P = 0.008) and +100 (P = 0.047) and a higher number of T lymphocytes and natural killer cells until day +365. The occurrence of graft vs. host disease (GVHD) was not influenced in our cases by DC1/DC2 graft composition, but patients with acute GVHD when compared with patients without acute GVHD presented a significantly less rapid DC recovery (DC1 P = 0.03, DC2 P = 0.009 on day +30, and DC1 P = 0.012, DC2 P = 0.006 on day +100). At the moment of relapse, a decrease of DC1/DC2 numbers was observed in four patients and the presence of two different DC populations one with a normal karyotype, and the other with the same cytogenetic abnormality as the malignant clone was detected by fluorescence in situ hybridization analysis. In conclusion, these observations suggest that in allogeneic HSCT recipients, DC recovery is a slow process possibly contributing to the high risk of infections in the post-transplant period and is possibly influenced by the source of HSC, the occurrence of GVHD and relapse. Further studies are warranted to investigate the significance of DC reconstitution in the transplant setting.

Adolescent↗
PubMed2004

Combination of rituximab, cyclophosphamide, and vincristine induces complete hematologic remission of splenic marginal zone lymphoma.

Optimal treatment for splenic marginal zone lymphoma (MZL) is not clearly established. Splenectomy has been proposed as the treatment of choice in patients with cytopenias and/or symptoms caused by an enlarged spleen. Splenic MZL, which expresses the CD20 antigen on tumor cell surfaces, is a disease entity candidate to treatment with anti-CD20 monoclonal antibodies. We employed an immunochemotherapy regimen with rituximab/cyclophosphamide/vincristine in 3 patients with splenic MZL who had only a partial response following CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) or CHOP-like therapy. The immunochemotherapy regimen was well tolerated and all patients exhibited complete remission. To our knowledge, this is the first report of splenic MZL showing response to a combination of rituximab with chemotherapy.

Antibodies, Monoclonal↗
PubMed2003

Clinical utility of the absolute number of circulating CD34-positive cells in patients with chronic myeloproliferative disorders.

BACKGROUND AND OBJECTIVES: Flow cytometry enumeration of peripheral blood CD34-positive cells provides reliable measurements of circulating hematopoietic progenitors in humans. Since the absolute number of circulating CD34-positive cells has been previously found to be elevated in myelofibrosis with myeloid metaplasia (MMM), we prospectively studied the clinical utility of this parameter in the work-up of patients with chronic myeloproliferative disorders. DESIGN AND METHODS: Of the 248 consecutive patients enrolled in this study, 106 had polycythemia vera (PV), 90 essential thrombocythemia (ET), and 52 myelofibrosis with myeloid metaplasia (MMM). The study population included both newly diagnosed and established cases, and of these latter some patients were on cytoreductive treatment while others were chemotherapy naive. Both cross-sectional and longitudinal investigations were carried out. Flow cytometry enumeration of CD34-positive cells was performed using a single-platform assay. RESULTS: Median numbers and ranges of circulating CD34-positive cells were 2.3x10(6)/L (0-5) in 20 control subjects, 2.2x10(6)/L (0-14) in those with PV, 2.4x10(6)/L (0-14) in those with ET, and 114x10(6)/L (6-2,520) in MMM patients. Analysis of variance demonstrated that values were markedly higher in MMM patients than in the remaining groups, and counts did not appear to fluctuate over short periods of follow-up. In both cross-sectional and longitudinal investigations on patients at clinical onset and/or out of cytoreductive treatment, a CD34-positive count of > or = 15x10(6)/L was always associated with MMM, clearly indicating a disease-related specificity. INTERPRETATION AND CONCLUSIONS: The absolute number of circulating CD34-positive cells is normal or anyhow lower than 15x10(6)/L in patients with uncomplicated PV or ET, whereas it is equal or above this cut-off in those with MMM, likely reflecting abnormal hematopoietic progenitor cell trafficking. Thus, enumeration of circulating CD34-positive cells may be useful in the work-up of patients with myeloproliferative disorders.

Adolescent↗
PubMed2002

Multidimensional flow cytometry immunophenotyping of hematologic malignancy.

Immunophenotyping of hematologic malignancies represents one of the most relevant clinical applications of flow cytometry. Classically, leukemic/lymphomatous cells have been considered to reflect the immunophenotypic characteristics of different precursors and mature healthy cells blocked at certain differentiation stages. Recently, accumulating evidence has shown that neoplastic cells display several aberrant phenotypic patterns. These aberrant phenotypes are believed to reflect genetic abnormalities present in pathologic cells, and recent data have shown that at least in acute leukemias, myelodysplastic syndromes, chronic lymphoproliferative disorders, and plasma cell dyscrasias, they may be present in almost all patients. The aim of this work is to review recent advances in flow cytometry and the role of gating strategies more useful in the identification and characterization of neoplastic cells of different hematologic malignancies.

ADP-ribosyl Cyclase↗