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Sickle cell disease (SCD) is a common inherited condition in African, Caribbean, and Mediterranean countries. SCD is a hematologic disorder caused by a well-characterized point mutation in the β-globin gene, which produces an abnormal hemoglobin S that results in the sickling of red blood cells in deoxygenated conditions. Patients with SCD display a “hypercoagulation state” leading to an increased risk of severe venous and arterial thrombotic vascular events. Herein we report a case of severe thrombotic complications in a patient with SCD who showed high antiphospholipid antibodies (APA) levels during vascular occlusions.

mRNA/cDNA gene expression of both small leucine-rich proteoglycans decorin and biglycan was evaluated by PCR real time in lymphocytes collected from patients with chronic lymphocytic leukaemia (CLL) at different stages of disease and from healthy controls. Lymphocytes obtained from healthy controls showed no or very low levels of mRNA expression of both decorin and biglycan. Biglycan expression was very low in CLL patients, values being close to those of controls. On the contrary, decorin mRNA was clearly expressed in patients with early B-cell CLL, while a low expression was found in advanced clinical stages. Furthermore, a significant higher decorin expression was found in patients with non-progressive CLL type in comparison with patients with aggressive type of the disease. Decorin expression resulted especially high in the low-progressive low-risk patients. The synthesis of decorin was also assessed by Western blot analysis. The peculiar occurrence of decorin in the non-aggressive type of CLL is consistent with its suggested anti-oncogenic role. Intracellular Bcl-2 level does not correlate with decorin mRNA transcription, suggesting that a Bcl-2 independent anti-cancer mechanism may occur. The measurement of galactosamine-containing proteoglycans concentration in plasma confirmed decorin expression results, with significant differences between CLL patients and controls. Significant changes were also seen between groups of patients of Rai stage 0 with recent diagnosis (less than 5 years, from analysis), (low amount of decorin) and less recent diagnosis (more than 5 years), (high amount of decorin).

The system involving angiopoietin-2 (Ang-2) and its receptor, Tie-2, appears to play an important role not only in tumor angiogenesis, but also in the biology of haematological and non-haematological malignancies. In the present study we evaluated the serum levels of soluble Ang-2 (sAng-2) and soluble Tie-2 (sTie-2) in patients with haematological malignancies. Measurements were carried out in 15 patients with chronic myeloid leukaemia (CML), 25 with essential thrombocythemia (ET), 24 with multiple myeloma (MM) and six with monoclonal gammopathy of undetermined significance (MGUS). In addition, we correlated the levels of angiopoietins with known prognostic factors. sAng-2 and sTie-2 were quantified with enzyme-linked immunosorbent assay (ELISA). In patients with CML and MM the levels of sAng-2 were significantly higher (1686.53 +/- 936.41 pg/mL and 1917.82 +/- 1427 pg/mL, respectively) than in controls (n = 15; 996.096 +/- 414.65 pg/mL) (P < 0.01). In patients with MM sAng-2 levels were significantly increased with increasing stage of disease, from stage I to stage III (P < 0.03) and presented a trend of correlation with Beta2-microglobulin levels (r = 0.317) and grade of bone involvement. Furthermore, the levels of sAng-2 determined after 6 months of chemotherapy in CML patients were significantly lower than at diagnosis in the patients who achieved haematological remission. Circulating sTie-2 levels were increased in patients with ET (17.5 +/- 9.2 vs 9 +/- 3.5 ng/mL; P < 0.01) and in those with CML (16.29 +/- 8.7 ng/mL; P < 0.04). In conclusion, abnormal levels of sAng-2 and sTie-2 are present in some haematological malignancies. These markers may play a role in the pathophysiology of these conditions and their progression.

The recent development of reduced intensity conditioning and allotransplantation (RICT) has opened a new way to assure engraftment of donor cells while reducing early transplant-related mortality. We evaluated the combination of high-dose therapy and autologous peripheral blood stem cells transplantation (APBSCT) followed by RICT to extend the benefit of allografting procedures in de novo multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51 years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony-stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6 patients developed chronic GVHD; 4 patients developed CMV antigenemia and were treated pre-emptively with ganciclovir. No transplant related mortality was shown. Response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF); when IF was negative, patients were classified in complete remission (CR) and when it remained positive, near CR (nCR). After a median follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and progression-free, respectively. Overall, the CR + nCR rate after dose-reduced allograft was enhanced from 26.7 to 73.3%. A correlation not statistically significant between GVHD and remission was found. In conclusion, an up-front tandem strategy with a very low reduced intensity-conditioning regimen for allografting following autografting is feasible and induces high CR/nCR rate in MM.

Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid leukaemia and myelodysplastic syndromes, but no data are available on sAng in chronic myeloproliferative disorders (CMD). Therefore, in this study we investigated the clinical significance of the angiogenin in sera of patients with chronic myeloid leukaemia (CML) (n = 14) or essential thrombocythaemia (ET) (n = 20), and correlated them with those of soluble transforming growth factor-beta(1) (sTGF beta(1)). Enzyme-linked immunosorbent assay detected (P < 0.05) higher levels of sAng in CMD compared with healthy subjects (1026.74 +/- 464.60 pg/mL and 196.00 +/- 39.90 pg/mL, respectively). The highest levels of sAng were detected in CML patients (1349.23 +/- 549.55 pg/mL). Interestingly, CML patients who achieved haematological remission after interferon therapy showed circulating levels of angiogenin significantly (P < 0.05) decreased when compared with those at diagnosis. In ET patients, levels of angiogenin (889.34 +/- 267.66 pg/mL) and sTGF beta(1) (76.69 +/-6.08 pg/mL) were higher (P < 0.05) compared with healthy controls (57.93 +/- 19.39 pg/mL). No correlation was found between levels of sAng and levels of sTGF beta(1) or platelet count among ET patients. Our results show for the first time that elevated blood levels of angiogenin feature chronic myeloid malignancies, suggesting a role of angiogenin in the pathogenesis of these diseases.

Interleukin-16 (IL-16), also named lymphocytic chemoattractant factor, is produced mainly by CD8+ peripheral blood lymphocytes but also by CD4+ T cells, eosinophils, mast cells, and bronchial epith...

In an article recently published in Leukemia and Lymphoma, Pozzi et al. reported 35 cases of bisphosphonate-associated osteonecrosis of the jaw (ONJ) in multiple myeloma patients [1]. In fact, sinc...

Authors evaluated some markers of angiogenetic activity in patients with chronic myeloproliferative diseases (CMDs). In this study by using a cytofluorimetric analysis we evaluated circulating endothelial progenitor cells (EPCs) in patients with chronic myeloproliferative disease. Moreover, in the same group of subjects, we evaluated serum levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2). In our patients, we have found an increase in the number of endothelial progenitor cells in primary myelofibrosis (PMF) and polycythaemia vera (PV) patients, while an increase of circulating endothelial cells (CECs) was found in all patients with CMD. Moreover, we found higher serum levels of VEGF with respect to control subjects in every group of patients with CMD, and a not significant reduction of VEGFR2 levels in essential thrombocythaemia (ET) patients. A correlation was also found in PV patients between VEGF levels and erythrocyte number and in PMF subjects with the count of white cells. Our data suggest that some markers of angiogenesis are activated in CMD patients and angiogenesis may have a role in the pathophysiology of chronic myeloproliferative disorders.

Osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates is a newly described entity. To elucidate the mechanism leading to ONJ and to test the hypothesis that in patients with ONJ the bisphosphonates may interfere with endothelial cell proliferation, using flow cytometric analysis we evaluated the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in eight patients with bisphosphonate treatment and osteonecrosis, eight multiple myeloma (MM) patients with bisphosphonates treatment without ONJ and five normal subjects. MM patients showed an increase of CD34+ cells with respect the control subjects and ONJ subjects. EPCs and CECs were higher in MM patients compared to controls and ONJ patients. ONJ patients showed a decrease of EPCs compared to control subjects while CECs were similar to the controls group. Our results seem to show the possibility that bisphosphonates could have a antiangiogenic effect and a suppressive effect on CECs of patients with ONJ.

Osteonecrosis of the jaw is an unremitting adverse outcome associated with bisphosphonate therapy in patients with multiple myeloma or bone metastases from solid tumors. Twelve patients who presented with exposed bone associated with bisphosphonates were reviewed to determine the type, dosage and duration of their bisphosphonate therapy, presenting findings, comorbidities and the event that incited the bone exposure. The discontinuation of bisphosphonate therapy has not helped reverse the presence of osteonecrosis, and the surgical manipulation of the involved site appears to worsen the underlying bone pathology. Hyperbaric oxygen, which has proven efficacious in other forms of osteonecrosis by establishing an oxygen gradient, is of no definitive benefit to patients with bisphosphonate-induced exposed bone. Antibiotic therapy is useful in controlling pain and swelling but ineffective in preventing the progression of the exposed bone. To date, prevention is the only currently possible therapeutic approach to the management of this complication.

Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid leukaemia and myelodysplastic syndromes, but no data are available on sAng in chronic myeloproliferative disorders (CMD). Therefore, in this study we investigated the clinical significance of the angiogenin in sera of patients with chronic myeloid leukaemia (CML) (n = 14) or essential thrombocythaemia (ET) (n = 20), and correlated them with those of soluble transforming growth factor-beta(1) (sTGF beta(1)). Enzyme-linked immunosorbent assay detected (P0.05) higher levels of sAng in CMD compared with healthy subjects (1026.74 +/- 464.60 pg/mL and 196.00 +/- 39.90 pg/mL, respectively). The highest levels of sAng were detected in CML patients (1349.23 +/- 549.55 pg/mL). Interestingly, CML patients who achieved haematological remission after interferon therapy showed circulating levels of angiogenin significantly (P0.05) decreased when compared with those at diagnosis. In ET patients, levels of angiogenin (889.34 +/- 267.66 pg/mL) and sTGF beta(1) (76.69 +/-6.08 pg/mL) were higher (P0.05) compared with healthy controls (57.93 +/- 19.39 pg/mL). No correlation was found between levels of sAng and levels of sTGF beta(1) or platelet count among ET patients. Our results show for the first time that elevated blood levels of angiogenin feature chronic myeloid malignancies, suggesting a role of angiogenin in the pathogenesis of these diseases.