Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly (age >or=65 yr), where it generally presents as a chronic disease. The objective of the present study was to describe the natural history of ITP in the elderly and to evaluate the risk of bleeding and the possible occurrence of other pathologies. We retrospectively evaluated 178 ITP patients (82 men, 96 women; mean age: 72 yr) diagnosed between 1981 and 1998. Therapy was started at diagnosis or during follow-up, depending on the platelet count and/or bleeding events. Sixty-six out of one hundred and seventy-eight patients (37%) initiated therapy at diagnosis; whereas in 11 of the 112 untreated patients (9.8%) therapy was necessary during the follow-up. Low-dose of prednisone was the first-line treatment in all patients (mean daily dose of 0.43 mg/kg). Forty-nine (63.6%) of the seventy-seven treated patients showed a response, 14 of these (28.6%) suffered a relapse. Another pathology occurred in 19 of the 178 patients (10.7%). We conclude that low-dose prednisone is an appropriate initial treatment for elderly persons. We also stress that an adequate follow-up is advisable, given that isolated thrombocytopenia could in some cases be the first sign of another underlying pathology.

Summary. Essential thrombocythaemia (ET) is usually considered an indolent disease, but it may progress during its natural course into acute leukaemia (AL); however, an influence of myelosuppressive agents in the blastic transformation of ET cannot be excluded. We performed a retrospective study to assess the incidence of AL in ET patients treated with pipobroman (PB) as first-line therapy. One hundred and sixty-four patients with ET were managed with PB at a dose of 1 mg/kg/d until a stable platelet count below 400 · 10 9 /l was achieved. Maintenance therapy was given at a planned dose ranging between 0AE2 and 1 mg/kg/d according to platelet count, in all cases, with a median daily dose of 25 mg (range 7-75 mg/d). The median treatment time was 100 months (range 25-243 months). The patients were evaluated for the occurrence of AL and/or secondary malignancies and survival end-points. AL was observed in nine patients (5AE5%) after a median treatment time of 153 months (range 79-227 months). The overall survival (OS) and the event-free survival (EFS) at 120 months were 95% and 97%, whereas at 180 months, they were 84% and 76% respectively. In conclusion, this retrospective analysis shows a low incidence of AL in a large group of patients consecutively treated with PB as first-line chemotherapy. Therefore, an investigation of the role of myelosuppressive agents in the blastic transformation of ET would be of interest.

Spontaneous occurrence of an acquired inhibitor to factor VIII (FVIII) is a rare event. About 50% of cases are idiopathic. Among younger people, inhibitors are often found in the postpartum period. Treatment must be administered either to overcome haemorrhagic symptoms or to eradicate the inhibitor. Several approaches have been proposed for inhibitor eradication, based on immunosuppressive drugs such as corticosteroids, cyclophosphamide and azathioprine, with varying results. High-dose immunoglobulin (HDIg) has been recently proposed as first-line therapy. We report on four cases with acquired inhibitor to FVIII occurring 4-8 months after delivery. At diagnosis, inhibitor titre was < 5 Bethesda units mL(-1) (BU mL(-1)) in three cases and > 5 BU mL(-1) in one. Factor VIII coagulant activity (FVIII:C) was < 1 U dL(-1)> in three cases and 12 U dL(-1) in one. We treated the patients with HDIg (400 mg kg-1 day(-1) for 5 consecutive days) and dexamethasone (24 mg day(-1) for 5-7 consecutive days), administered at the same time. In three women, the inhibitor was suppressed in 2-50 weeks. After an off-therapy period ranging from 20 to 104 weeks, the FVIII:C was persistently normal and the inhibitor undetectable. The fourth woman remained unresponsive. In two cases, recombinant activated factor VII administration stopped the bleeding. Thus, intermediate- to high-dose dexamethasone and HDIg given at the same time could be a successful and safe therapeutic approach for a rapid and complete remission from the development of FVIII inhibitors.

Spontaneous occurrence of an acquired inhibitor to factor VIII (FVIII) is a rare event. About 50% of cases are idiopathic. Among younger people, inhibitors are often found in the postpartum period. Treatment must be administered either to overcome haemorrhagic symptoms or to eradicate the inhibitor. Several approaches have been proposed for inhibitor eradication, based on immunosuppressive drugs such as corticosteroids, cyclophosphamide and azathioprine, with varying results. High-dose immunoglobulin (HDIg) has been recently proposed as first-line therapy. We report on four cases with acquired inhibitor to FVIII occurring 4-8 months after delivery. At diagnosis, inhibitor titre was < 5 Bethesda units mL(-1) (BU mL(-1)) in three cases, and > 5 BU mL(-1) in one. Factor VIII coagulant activity (FVIII:C) was < 1 U dL(-1) in three cases and 12 U dL(-1) in one. We treated the patients with HDIg (400 mg kg(-1) day(-1) for 5 consecutive days) and dexamethasone (24 mg day(-1) for 5-7 consecutive days), administered at the same time. In three women, the inhibitor was suppressed in 2-50 weeks. After an off-therapy period ranging from 20 to 104 weeks, the FVIII:C was persistently normal and the inhibitor undetectable. The fourth woman remained unresponsive. In two cases, recombinant activated factor VII administration stopped the bleeding. Thus, intermediate- to high-dose dexamethasone and HDIg given at the same time could be a successful and safe therapeutic approach for a rapid and complete remission from the development of FVIII inhibitors

MUC1 is a glycoprotein expressed on the luminal surface of simple epithelia. In carcinoma, MUC1 overexpression is associated with malignancy. In breast cancer patients, increased levels of circulating MUC1 (CA 15.3 tumor marker) are associated with poor prognosis (Tumour Biol.2005; 26:217–20). In myeloma, MUC1 overexpression correlates with apoptosis resistance. We have previously shown (Br J Haematol.2003; 120:344–52) that MUC1 is selectively found in differentiating erythroid cells suggesting a possible role as cross-talk molecule between erythroblasts and bone marrow microenvironment during erythropoiesis. In CD34+ cells cultured in the presence of EPO and SCF, MUC1 is expressed before Glycophorin A (GlyA) during the erythroid differentiation process, and disappears following GlyA up-regulation. Aiming to evaluate the role of MUC1 in the erythroid counterpart present in neoplastic haemopoiesis, we studied MUC1 serum circulating levels in patients affected by Ph-negative Myeloproliferative Chronic Disorders (MPD). We analysed serum samples from 42 MPD patients affected by Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) (N 25, 14, and 3, respectively). CA15.3 (soluble MUC1) levels were determined using the commercially available ADVIA Centaur CA 15.3 assay (Bayer Corporation, NY) and cut off level was set at 25 U/mL. As control group serum samples from healthy donors, matched for sex and age, were also analyzed. Evaluation of the humoral immune response to MUC1 protein core was performed in ELISA. Results indicated that CA15.3 levels were statistically higher in MPD patients than in the control group (p&lt;0.005), this difference was more evident in PV patients (p&lt;0.001) and in female cases (p&lt;0.001). The JAK2V617F mutation status was not associated with CA15.3 values; similarly, neither the clinical or hematological features nor the clinical complications (thrombosis) were influenced byCA15.3 levels. Analysis of the humoral immune response to MUC1 core protein showed no substantial changes in serum anti-MUC1 IgG titers in PV patients, suggesting that in PV increase of soluble MUC1 does not induce immune responses against this self-antigen. Further studies are ongoing to investigate the significance of MUC1 in the development and onset of myeloproliferative disorders. In conclusion, MUC1 levels seem to be increased in PV patients, suggesting that further evaluations on large series of cases should include this test in the diagnostic work-up to PV patients.