Low dose gemtuzumab ozogamicin for relapsed acute myeloid leukaemia in elderly

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Atypical presentations of thrombotic thrombocytopenic purpura in middle-aged women with recurrent cerebral macrovascular thrombosis: a case report

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A novel assay to detect calreticulin mutations in myeloproliferative neoplasms

The myeloproliferative neoplasms are chronic myeloid cancers divided in Philadelphia positive (Ph+), chronic myeloid leukemia, or negative: polycythemia vera (PV) essential thrombocythemia (ET), and primary myelofibrosis (PMF). Most Ph negative cases have an activating JAK2 or MPL mutation. Recently, somatic mutations in the calreticulin gene (CALR) were detected in 56–88% of JAK2/MPL-negative patients affected by ET or PMF. The most frequent mutations in CARL gene are type-1 and 2. Currently, CALR mutations are evaluated by sanger sequencing. The evaluation of CARL mutations increases the diagnostic accuracy in patients without other molecular markers and could represent a new therapeutic target for molecular drugs. We developed a novel detection assay in order to identify type-1 and 2 CALR mutations by PNA directed PCR clamping. Seventy-five patients affected by myeloproliferative neoplasms and seven controls were examined by direct DNA sequencing and by PNA directed PCR clamping. The assay resulted to be more sensitive, specific and cheaper than sanger sequencing and it could be applied even in laboratory not equipped for more sophisticated analysis. Interestingly, we report here a case carrying both type 1 and type2 mutations in CALR gene

Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial

BACKGROUND: The aim of this study was to investigate the role of pre-treatment aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) + bevacizumab (B) or CT alone. PATIENTS AND METHODS: Patients randomly received CT+B or CT alone as first-line therapy. CT consisted of either FOLFOX4 or FOLFIRI at the clinician's discretion. RESULTS: Out of the 284 patients enrolled, increased ALRI levels were associated with shorter PFS and OS (p<0.0001). At baseline, median PFS was 10.3 months (95% CI 9.4-12.0) and 8.0 months (95 % CI 6.8-8.9), and median OS was 25.2 months (95 % CI 21.3-30.2) and 18.8 months (95 % CI 16.6-21.7) for patients with low (<14) and high (≥14) ALRI levels, respectively (HR 1.43, 95% CI 1.12-1.82, p=0.004; HR=1.51, 95% CI 1.17-1.96, p<0.001). Interaction tests on ALRI levels and treatment efficacy in the CT+B and the CT groups were statistically significant for PFS (p=0.0003), but not for OS (p=0.228). CONCLUSION: Our results indicate that ALRI is a good prognostic and predictive marker for mCRC patients candidate for CT+B

An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia

Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs

Persistence of chromosomal abnormalities additional to the Philadelphia chromosome after Philadelphia chromosome disappearance during imatinib therapy for chronic myeloid leukemia

Five Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) patients with additional chromosome abnormalities at diagnosis have been followed during Imatinib therapy. In all, the Ph chromosome disappeared, while the 5 cases, additional abnormalities [dup(1); del(5), +8 (2 patients) and +14] persisted in the subsequent studies, performed over a period of 11 to 49 months, either alone or together with a karyotypically normal cell population. This finding is consistent with a secondary origin of the Ph chromosome in these patients. It is still to early to evaluate the possible prognostic value of these additional abnormalities

Degradation of magnetic nanoparticles mimicking lysosomal conditions followed by AC susceptibility

[Background] A deeper knowledge on the effects of the degradation of magnetic nanoparticles on their magnetic properties is required to develop tools for the identification and quantification of magnetic nanoparticles in biological media by magnetic means.[Methods] Citric acid and phosphonoacetic acid-coated magnetic nanoparticles have been degraded in a medium that mimics lysosomal conditions. Magnetic measurements and transmission electron microscopy have been used to follow up the degradation process.[Results] Particle size is reduced significantly in 24 h at pH 4.5 and body temperature. These transformations affect the magnetic properties of the compounds. A reduction of the interparticle interactions is observed just 4 h after the beginning of the degradation process. A strong paramagnetic contribution coming from the degradation products appears with time.[Conclusions] A model for the in vivo degradation of magnetic nanoparticles has been followed to gain insight on the changes of the magnetic properties of iron oxides during their degradation. The degradation kinetics is affected by the particle coating, in our case being the phosphonoacetic acid-coated particles degraded faster than the citric acid-coated ones.LG is the beneficiary of a postdoctoral grant from the AXA Research Fund and GBdS, of a sandwich-PhD grant from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brazil). This work was also supported by the 7th framework programme of the European Commission Directorate-General for Research and Innovation (Nanomag 604448). X-ray diffraction, FTIR spectroscopy, and thermogravimetric and chemical analysis were carried out in the support laboratories of Instituto de Ciencia de Materiales de Madrid (CSIC).Peer reviewe

Melphalan-prednisone versus alternating combination VAD/MP or VND/MP as primary therapy for multiple myeloma: final analysis of a randomized clinical study

In the absence of a cure for multiple myeloma (MM) with standard-dose therapy, any strategy that can be expected to increase tumor reduction and to extend survival duration is likely to be of clinical relevance. The primary end-point of the present study was to investigate whether the alternating combination of vincristine-doxorubicin-dexamethasone (VAD) and melphalan-prednisone (MP) or vincristine-mitoxantrone-dexamethasone (VND) and MP could improve the clinical outcome of MM patients thus treated in comparison with those receiving MP alone

Melphalan-Prednisone Versus Alternating

roups was not statistically significant, even after stratifying patients into high-risk and low-risk subgroups, as assessed by a multifactor proportional hazard analysis. In both younger and elderly patients, severe granulocytopenia and related infections were significantly more frequent with VND/MP compared to the remaining arms of treatment (p < 0.001 and p = 0.009, respectively). Similarly, the frequency of WHO grade III-IV cardiovascular events was significantly higher for patients receiving anthracycline-containing regimens (VND/MP and VAD/MP) than for those treated with MP alone (p = 0.04). P rogress toward improving the prognosis of multiple myeloma (MM) with standard-dose therapy has been modest since the early 1960s. Intermittent melphalan-prednisone (MP) is still considered at many centers the treatment of choice for patients not eligible for high-dose therapy. It produces a response rate of approximately 50-55% and a median survival averaging 3 years. Extens