Light and electron microscopic study of cyclosporin A-induced gingival hyperplasia

Four transplant (3 kidney, 1 bone marrow) patients with cyclosporin A (CyA)-induced gingival hyperplasia are described. Light and electron microscopic findings of gingival biopsies showed in all patients that, in addition to an increase of collagen, CyA induced in the subepithelial space an enormous infiltration of morphologically normal plasma cells in different stages of maturation. These data, together with the reversibility of the lesion upon discontinuation of the drug, suggest that individual hypersensitivity is probably the most acceptable explanation of CyA-induced gingival hyperplasia. This hypothesis is also discussed in relation to the CyA-suppression of the functions of some T-lymphocyte subsets

High prevalence of heparin induced thrombocytopenia with thrombosis among patients with essential thrombocytemia carrying V617F mutation

Arterial and venous complications are major causes of morbidity and mortality in myeloproliferative neoplasms (MPNs). MPNs patients, frequently receive heparin. Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening complication resulting in a severe acquired thrombophilic condition. We carried out a retrospective analysis to evaluate occurrence of new thrombotic events during heparin therapy in essential thrombocythemia (ET) patients. We studied 108 ET patients on heparin for treatment of previous thrombotic events or in thromboprophilaxis. Fifty-eight of them carried JAK 2 V617F mutation while 50 patients were without V617F mutation. Ten patients, among those with JAK 2 V617F mutation after a median of 10 days from heparin treatment presented a platelet drop, new thrombotic events and in 10/10 cases heparin-related antibodies were found. In the other group, two patients (4%) presented a platelet drop, thrombotic manifestations and heparin related antibodies. Our data show that HIT is more frequent, during heparin treatment, in patients with ET carrying V617F mutation, as compared with patients without mutations (P = 0.029). ET with V617F mutation seems to be associated with higher risk of thrombotic complications during heparin treatment. Monitoring platelet counts very closely during the course of heparin is essential especially in ET patients in which platelet drop may be hidden by constitutional thrombocytosis

VEGF expression correlates with microvessel density in Philadelphia chromosome-negative chronic myeloproliferative disorders

We examined microvessel density (MVD) and immunohistochemical expression of vascular endothelial growth factor (VEGF) in the bone marrow biopsy specimens of 98 patients with Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders (CMPDs). There were significantly more MVD "hot spots" in chronic idiopathic myelofibrosis (CIMF; mean \ub1 SD, 25.6 \ub1 6.3) and polycythemia vera (PV; 20.7 \ub1 10.2) cases than in essential thrombocythemia (ET) cases (10.1 \ub1 4.5) and normal control (NC) samples (7.5 \ub1 3.6) (P < .05). Similar results were found using a semiquantitative method (P < .0001). A calculated VEGF index (VEGF (i)) was higher in CIMF (0.29 \ub1 0.15) and PV (0.28 \ub1 0.20) cases than in ET (0.12 \ub1 0.05) and NC (0.08 \ub1 0.04) cases (P < .0001). MVD and VEGF(i) were higher in the myelofibrotic phases of CIMF and PV. There was a direct correlation between VEGF(i) and MVD when considering the Ph- CMPDs together (v = 0.67; P < .001) and when considering PV (r = 0.79; P < .001) and CIMF (r = 0.40; P = .013) as individual entities. Our data could provide a rationale for directly targeting VEGF or endothelial cells in CIMF and PV

Increased expression of vascular endothelial growth factor receptor 1 correlates with VEGF and microvessel density in Philadelphia chromosome-negative myeloproliferative neoplasms

AIMS: The authors investigated vascular endothelial growth factor receptor 1 (VEGFR-1) protein expression in a series of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs) and its correlations with microvessel density (MVD) and vascular endothelial growth factor (VEGF). METHODS: 83 bone marrow biopsies of Ph- MPNs patients, including 27 essential thrombocythaemia (ET), 21 polycythaemia vera (PV) and 35 primary myelofibrosis (PMF), and 10 normal controls (NCs) were investigated by immunohistochemistry. RESULTS: Patients with PV and PMF showed an increased MVD (PV: 20.1\ub110.6; PMF: 25.8\ub16.5) compared with those with ET or NCs (ET: 10.4\ub14.6; NCs: 7\ub13.4). VEGFR-1 expression was increased in Ph- MPNs, particularly in PV and PMF (NCs: 0.07\ub10.03; ET: 0.15\ub10.09; PV: 0.31\ub10.2; PMF: 0.31\ub10.04). VEGF expression parallelled VEGFR-1 and resulted increased in Ph- MPNs (NCs: 0.08\ub10.04; ET: 0.13\ub10.06; PV: 0.29\ub10.2; PMF: 0.31\ub10.15) and higher in post-polycythaemic myelofibrosis and in the fibrotic stage of PMF than in the non-fibrotic phases of both diseases. VEGFR-1 protein expression correlated with MVD and VEGF expression in Ph- MPNs. VEGFR-1 and VEGF were expressed by the same bone marrow populations: megakaryocytes, macrophages and immature myeloid precursors showed a moderate to strong immunostaining intensity in both Ph- MPNs and NCs. The erythroid precursors were not immunoreactive. CONCLUSIONS: VEGFR-1 and VEGF were increased and co-localised in megakaryocytes, macrophages and myeloid precursors of Ph- MPNs. This finding supports the hypothesis of a VEGF/VEGFR-1 autocrine loop in the neoplastic cells of Ph- MPNs

Low-Dose Cytosine Arabinoside (ARA-C) Therapy in the Myelodysplastic Syndromes and Acute Myelogenous Leukemia.

Clinical study on the use of low-dose cytosine arabinoside (Ara-C) in the treatment of myelodysplastic syndromes and acute myelogenous leukemia

Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and S&#233;zary syndrome : a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation

Purpose: To analyze the outcome of allogeneic transplantation for mycosis fungoides and S\ue9zary syndrome (MF/SS) in terms of nonrelapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) and to identify factors associated with the outcome. Patient and Methods: Sixty patients with MF (n = 36) and SS (n = 24) who received a first allogeneic hematopoietic cell transplantation (HCT) from a matched related (mRD; n = 45) or unrelated donor (mUD; n = 15) between 1997 and 2007 and who were registered in the European Group for Blood and Marrow Transplantation database were analyzed: 37 men and 23 women, median age 46.5 years (range, 22 to 66 years). Forty-four patients had TNM stage IV, and 40 patients were at advanced phase at transplantation. Forty-four patients received reduced-intensity conditioning (RIC) regimens, and 25 underwent T-cell depletion (TCD). Results: Allogeneic transplantation in MF/SS offers an estimated OS of 66% at 1 year and 54% at 3 years, primarily driven by donor type, disease phase, and type of conditioning. RIC decreased NRM (relative risk [RR] = 4.7; P = .008) without increasing REL, leading to a higher OS (RR = 2.8; P = .03). Advanced-phase disease increases REL (RR = 3.0; P = .03) and reduces PFS (RR = 4.4; P = .002) and OS (RR = 3.5; P = .023). Recipients of mRD allogeneic HCT had better PFS (RR = 2.7; P = .006) and OS (RR = 4.0; P = .001) than their mUD counterparts. The risk of REL increases with TCD (RR = 3.2; P = .005). Some patients who experience relapse can successfully undergo rescue treatment with donor lymphocyte infusions. Conclusion: Allogeneic transplantation is a valid therapeutic alternative for high-risk patients with advanced-stage MF/SS. Our data also suggest the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS

RIC vs. MAC followed by allogeneic stem cell transplantation for patients with MDS or secondary AML: A prospective, randomized phase III study of the CMWP of the EBMT (RICMAC-Trial)

Development and application of statistical models for medical scientific researc

RIC vs. MAC followed by allogeneic stem cell transplantation for patients with MDS or secondary AML: A prospective, randomized phase III study of the CMWP of the EBMT (RICMAC-Trial)

Development and application of statistical models for medical scientific researc