Low-dose thalidomide displays an acceptable toxicity profile and provides an objective and subjective advantage to a relevant portion of MMM patients.

APL harbors a strong in vitro antileukemic activity at a concentration achievable in patients at non-myelotoxic doses. Our data also support the notion of an impact on VEGF secretion. Clinical studies with this new marine-derived compound in relapsed/resistant leukemia are underway.

PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemiaAn increased incidence of thrombosis, both arterial and venous, has been reported in essential thrombocythaemia (ET) (Spivak et al, 2003). ET is considered as a 'clonal' myeloproliferative disorder, but studies of X-chromosome inactivation pattern (XCIP) indicated that a proportion of patients with ET, diagnosed according to the currently available criteria, presented polyclonal myelopoiesis (el-Kassar et al, 1997;Harrison et al, 1999a;Chiusolo et al, 2001;Shih et al, 2001Shih et al, , 2002. Since the rate of thrombosis in patients with polyclonal myelopoiesis was significantly lower than in monoclonal patients (Harrison et al, 1999a;Chiusolo et al, 2001;Shih et al, 2002), assessment of clonality would enable the identification of patients within different risk categories suitable for risk-adapted treatment strategies . However, beyond concerns as a result of age-dependent unbalanced X-chromosome skewing (Champion et al, 1997;Mitterbauer et al, 1999), the major limitation of XCIP analysis is that it can be performed only in women.No specific molecular marker of ET has been identified yet, although a number of cellular and molecular abnormalities have been described (Spivak et al, 2003); these include reduced platelet content of Mpl, the receptor for thrombopoietin (Horikawa et al, 1997;Harrison et al, 1999b;Li et al, 2000), spontaneous in vitro growth of erythroid progenitors (endogenous erythroid colonies, EEC) (Prchal & Axelrad, 1974;Kralovics et al, 2003) and overexpression of the PRV-1 gene (Teofili et al, 2002a;Johansson et al, 2003a;Liu et al, 2003;Tefferi et al, 2004). However, an association between these abnormalities and thrombosis has been reported only occasionally (Teofili et al, 2002b;Johansson et al, 2003b).The aim of this study was to assess whether any of these three epigenetic markers clustered with clonality status in females with ET; if so, it (they) might be considered to represent (a) 'surrogate marker(s)' of clonality and, possibly, of thrombotic risk. Patients and methodsOne hundred females with ET were studied; they comprised an unselected consecutive population of patients who attended the outpatient departments of our Haematology institutions for either diagnostic or routine follow-up purposes. Diagnosis SummaryFemales with the monoclonal type of essential thrombocythaemia (ET), based on the X-chromosome inactivation pattern (XCIP), have previously been shown to present a higher incidence of thrombosis than polyclonal ones. We aimed to assess correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P ¼ 0AE009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal su...

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Anemia is a common, but underestimated and undertreated, complication of patients with cancer receiving chemo-or radiotherapy, and negatively affects their quality of life (QoL). Erythropoietic proteins (EPS) offer an effective treatment of cancer anemia and ameliorate QoL, although their use requires the correct targeting of hemoglobin increase to avoid thromboembolic complications. Currently the effort is focused on offering patients this effective treatment with reduced frequency of administration. Higher weekly single doses of recombinant human Epo (rHuEpo) either alpha or beta, instead of three times per week, have been proposed for the treatment. The pharmacokinetic and pharmacodynamic characteristics of the hyperglycosylated protein darbepoetin alpha permit even longer intervals between administrations. Every other week or every three weeks schedules have shown results (erythropoietic response, reduction of transfusion requirements, and improvement of QoL) comparable with those of weekly rHuEpo.

BackgroundJoint involvement is one of the main causes of chronic pain and disability in SLE patients (pts); despite arthritis in SLE is usually considered mild, joint erosions and deformities can be observed with significant impact on patient's quality of life. Imaging techniques are more sensitive than joint count in detecting synovitis and early joint damage.ObjectivesThis study was aimed at evaluating the progression of joint damage in SLE and at evaluating predictive factors for damage accrualMethodsConsecutive SLE pts with active hand-wrists synovitis (detected by joint count and/or ultrasounds) were enrolled in this 5-years prospective observational study. Clinical assessments as well as joint ultrasound (US) and MRI were performed at baseline and after 5 years. Each patient underwent a non-dominant hand–wrist US examination using a Logiq 9 with a linear probe operating at 14 MHz. Synovitis was defined as the presence of synovial hypertrophy and/or the presence of power Doppler signal (PD). A non-dominant hand–wrist MRI study with a 0.3 T extremity dedicated machine to evaluate the presence of bone erosions (BE) and bone marrow edema (BME) was also performed. Coronal and axial T1-weighted gradient-echo images and coronal STIR images were acquired. The images acquired were scored according to the RAMRIS scoring system for RA by a trained radiologist unaware of the clinical picture and diagnosis.ResultsFifty-seven pts were enrolled (female 91.2%, mean age 44±12.2 years, mean disease duration 15.9±9 years);43 (75.4%) completed the follow-up, 3 died (5.2%) and 11 (19.4%) were lost to follow-up. At baseline, 7 (12.3%)satisfied criteria for Jaccoud arthropathy (JA) and 7 (12.3%) had a recent onset arthritis (<1 year of duration). 22 pts (28.6%) showed clinical signs of synovitis, 56 (98.2%) presented positive hand-wrists US (synovitis) and in 14 (24.6%) PD signal was also recorded. Six pts (11.76%) already showed erosions at standard X-Ray, while MRI revealed at least one BE in 30 and 54 patients respectively, for a cumulative mean erosive burden of 9.2 erosions (range 1–63). After 5 years of follow-up, 34 pts consented to repeat the assessment; 11 (33%) had JA and 18 (29%) were still presenting clinical signs of synovitis; 28 pts (82.3%) showed synovitis at US with PD in 7 cases (20.5%). The final mean erosive burden resulted 12.3 (range 2–82) with a significant increase from the baseline evaluation (p=0.001). Overall, 16 pts accrued joint damage. Interestingly, erosion progression was observed also in 12 pts with negative joint count but positive US at baseline. The presence of PD at US and BME at baseline was associated with higher erosive burden at follow-up (p=0.03 and p=0.02 respectively)ConclusionsArthritis in SLE can be persistent over time and progress to joint damage even in a short tem period despite treatment; normal joint count at physical examination but US findings of synovitis can be associated with erosion progression over time. The presence of PD at US and bone marrow edema at MRI are associated ...