A Case of Atypical Delayed and Prolonged Hematologic Toxicity With Azacitidine in Chronic Myelomonocytic Leukemia (CMML) and Review of Literature

Hypomethylating drugs are useful and have been approved for the treatment of myelodysplastic syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS, have included only a small number of patients with CMML, and there are just a few specific reports on CMML patients. The Azacitidine is actually authorised for the treatment of CMML patients with 10–29% marrow blasts without myeloproliferative disorder, who are not eligible for haematopoietic stem cell transplantation. This hypomethylating agent in MDS is known for causing transient cytopenias, most often occurring during the first 2 cycles. Here we report a case of an atypical delayed and prolonged hematologic toxicity during Azacitidine treatment in a CMML patient; furthermore we also reviewed the literature regarding the efficacy of the drug and the management of hematologic adverse effects, in term of dose adjustments or alternative schedule of administration, in specific CMML setting

Successful treatment with T depleted autologous peripheral blood stem cell transplantation of refractory chronic autoimmune thrombocytopenic purpura

Autoimmune thrombocytopenia (AITP) is a disorder due to specific platelet auto-antibodies directed against platelet surface glycoproteins. AITP in adults is usually chronic, idiopathic and frequently refractory to conventional treatments. Myelo- and immuno- suppressive chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation is an experimental approach for severe chronic refractory AITP. We report a case of a woman with AITP, refractory to the conventional therapy, submitted to T-cell-depleted autologous PBSC transplantation, which obtained long term stable response on platelet count. We deem that the positive outcome of our patient depends on T-cells depletion of the graft, which reduces autoreactive T clones

Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice

Thrombopoietin mimetics are new treatment options for patients with immune thrombocytopenia (ITP). Because of their mechanism of action, long-term administration was envisioned in order to maintain effective thrombopoiesis. We report on 30 romiplostim treated patients: 13/27 responders (48%) achieved stable platelet counts on a mean romiplostim dose of 2.43 μg/kg and were able to stop romiplostim after a mean of 44.3 weeks (range 12-122) on therapy with sustained response maintained at a mean of 26 months (range 12-52). No bleeding events occurred during the observational period. No specific patient’s features nor pattern of early response seemed to predict for sustained response. However, patients achieving safe platelet counts at lower dosages are probably worth a try of therapy tapering and discontinuation. Our observations support feasibility of romiplostim safe suspension in a relevant proportion of ITP patients

Estudo retrospectivo das afecções locomotoras em ruminantes atendidos na Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo entre 2000 e 2012

This study aimed to perform a retrospective study of ruminants attended at the Clinic for Cattle and Small Ruminants (CBPR) of the Faculty of Veterinary Medicine (FMVZ), University of São Paulo (USP) with locomotor diseases from 2000 to 2012. During this period 209 cases were treated. It was found that cases located in the distal limb and in the proximal region were 62.7% and 33.7%, respectively. In bovines, 121 (57.9%) cases were treated, with 86 (71.07%) cases presented in the distal limb and 35 (28.93%) cases in the proximal region. The most common disease was interdigital hyperplasia with 23 (26.74%) cases treated. Fractures were the most frequent disease related to the proximal region corresponding to 17 (48.6%) occurrences. In small ruminants, 88 animals (42.1%) were treated with 45 (51.1%) cases in the distal region and the other 43 (48.9%) in the proximal region. In these species, the foot-rot (60%) and fractures (77.4%) was the most common diseases found in the distal and the proximal region, respectively. The disorders of the locomotor system of ruminants were uncommon in the CBPR. While the affected animals with claw diseases have a good prognosis, disorders affecting the upper limb in cattle, mainly fracture, have a poor prognosis.Foi realizado o estudo retrospectivo das afecções do sistema locomotor de ruminantes atendidos no Serviço de Clínica de Bovinos e Pequenos Ruminantes da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (FMVZ-USP), no período de 2000 a 2012. Nesse período, foram atendidos 209 casos de animais com problemas locomotores, dos quais 62,7% localizados na região distal dos membros e 37,3% na região proximal. Na espécie bovina, com 121 (57,9%) casos atendidos, o comprometimento da região distal dos membros foi observado em 86 (71,07%) e da região proximal em 35 (28,93%) dos casos, respectivamente. A afecção mais frequente observada em bovinos foi a hiperplasia interdigital com 26,74% (23) dos casos atendidos. Entre as afecções na região proximal, houve maior ocorrência de fraturas, com 48,6% (17) dos casos. Foram atendidos 88 (42,1%) pequenos ruminantes, apresentando lesões na região distal em 51,1% (45) dos casos e 48,9% (43) com lesões na região proximal. Nessas espécies, as lesões de maior ocorrência nas regiões distais e proximais foram, respectivamente, o foot-rot (60%) e as fraturas (77,4%). As afecções do sistema locomotor dos ruminantes foram pouco frequentes entre os animais atendidos no período estudado. Quanto ao prognóstico, foi bom nos animais acometidos com doenças podais, diferentemente das afecções proximais dos bovinos, principalmente fraturas, que apresentaram prognóstico mau

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings

Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

<p>Abstract</p> <p>Background</p> <p>Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting.</p> <p>Objective</p> <p>To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method.</p> <p>Methods</p> <p>We cultured myeloma-positive CD34⁺PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34⁺cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture.</p> <p>Results</p> <p>Overall recovery of CD34⁺cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34⁺cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34⁺cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34⁺cell selection, and up to 2.3 logs after culture and ΔNGFR selection.</p> <p>Conclusion</p> <p>We conclude that <it>ex-vivo </it>culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.</p