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Objetivo: Avaliar o perfil epidemiológico dos pacientes oncohematológicos que receberam transfusão nas unidades de saúde atendidas pelo Grupo GSH no Brasil. Material e métodos: Estudo retrospectivo realizado através do levantamento de dados obtidos do sistema informatizado no período de janeiro de 2023 a junho de 2024, registrado pelas agências transfusionais do grupo GSH no Brasil. Os dados foram agrupados e analisados em planilha do programa Microsoft Excel, mensurando os resultados de acordo com idade, sexo, tipo de hemocomponente transfundido e diagnóstico. Resultados: No período do estudo foram avaliadas o total de 101.376 transfusões relacionadas a atendimentos a pacientes oncohematológicos. Com relação à idade dos receptores atendidos, observou-se 7.386 (7,3%) pacientes entre 1-15 anos, 12.273 (12,1%) pacientes entre 16-30 anos, 14.923 (14,7%) entre 31-45 anos, 22.194 (22%) entre 46-60 anos, 26.431 (26%) entre 61-75 anos, 16.115 (15,9%) 75-90 anos e acima de 90 anos, 2.054 (2%). As transfusões em pacientes do sexo masculino totalizaram 57.079 (56,3%), enquanto 44.297 (43,7%) ocorreram em pacientes do sexo feminino. Com relação ao tipo de hemocomponente, foram transfundidas 72.486 (71,5%) unidades de concentrado de plaquetas (randômicas e aféreses), 23.891 (23,5%) concentrados de hemácias, 2.836 (2,8%) unidades de crioprecipitado, 2.134 (2,1%) plasmas frescos congelados e 29 (0,1%) unidades de granulócitos. Quanto ao diagnóstico relatado nas requisições transfusionais, foram 1.558 (1,5%) transfusões referentes a transplante de medula óssea, 2.130 (2,1%) aplasia de medula, 10.449 (10,3%) síndrome mielodisplásica, 10.662 (10,5%) mieloma múltiplo, 11.330 (11,2%) linfomas e 65.287 (64,4%) leucemias. Discussão: Nesse estudo, observou-se a prevalência de transfusão de concentrado de plaquetas, representando 71,5% das transfusões realizadas, seguido da transfusão de concentrados de hemácias, resultado esperado como consequência das condições clínicas e laboratoriais dos pacientes, que são submetidos a tratamentos quimioterápicos, que tem como consequência anemia e plaquetopenia. Houve maior número de atendimento em pacientes do sexo masculino com 56,3%. Quanto a distribuição por faixa etária, realizou-se mais atendimentos em pacientes entre 61 e 75 anos, 26% dos casos. Com relação ao diagnóstico, 64,4% dos pacientes apresentavam leucemias. Conhecer o perfil dos pacientes, auxilia na seleção dos hemocomponentes, desenvolvendo protocolos específicos de hemocomponentes especiais, com utilização de hemocomponentes filtrados, irradiados e com fenotipagem para o Sistema Rh, com o objetivo de prevenir a ocorrência de reação transfusional e evitar a sensibilização. Conclusão: As doenças onco-hematológicas comprometem a medula óssea no momento do diagnóstico e durante o tratamento, portanto, são responsáveis pelo maior número de transfusões nas agências transfusionais. Entre essas doenças, as leucemias levam ao maior comprometimento medular, principalmente relacionado à queda no número de plaquetas que traz como principal consequência sangramentos, muitas vezes grave. Por isso, durante a análise desse estudo, observamos prevalência do diagnóstico de leucemia e da transfusão de concentrado de plaquetas como tipo de hemocomponente mais transfundido.

Objetivo: Descrever as principais reações transfusionais imediatas e tardias ocorridas em hospitais atendidos pelo Grupo GSH no país. Material e métodos: O levantamento dos dados, foi realizado pelas informações obtidas do sistema informatizado do Grupo GSH e da avaliação do livro de registro de notificações de reações transfusionais imediatas e tardias com o parecer do responsável médico, ocorridas no período de janeiro a dezembro de 2023, os dados são referentes à atendimentos de cerca de 240 hospitais e clínicas. Para a caracterização das reações transfusionais foram avaliadas quanto ao tipo de reação transfusional que podem ser classificadas como imediatas (aguda) ocorridas durante ou em até 24h da transfusão. E reações do tipo tardia que ocorrem após 24h até cerca de 3 semanas, após a transfusão. Resultado: Dos casos analisados, constatou-se que, das 390.000 bolsas transfundidas, 2.812 apresentaram sinais ou sintomas relacionados a reações transfusionais, afetando o total de 1.039 receptores. Isso representa um percentual de 0,72% de reações transfusionais. Das reações identificadas, suas causas foram classificadas das seguintes formas: 0,04% de distúrbios metabólicos (1 caso), 0,07% de dor aguda relacionada à transfusão (2 casos), 0,18% de reação hemolítica tardia (5 casos), 0,25% de outras reações tardias (7 casos), 0,3% de reação hipotensiva relacionada à transfusão (8 casos), 0,4% de reação hemolítica aguda imunológica (11 casos), 0,82% de lesão pulmonar aguda relacionada à transfusão (23 casos), 1,03% de dispneia associada à transfusão (29 casos), 1,21% de aloimunização/aparecimento de anticorpos irregular (34 casos), 4,1% de outras reações imediatas (116 casos), 5,7% de sobrecarga circulatória associada à transfusão (159 casos), 28,3% de reação febril não hemolítica (797casos) e 57,6% de reação alérgica (1620). Discussão: Durante os meses avaliados pode-se observar uma maior incidência das reações imediatas com 98,36%, com predominância dos tipos alérgica com 57,6% e febril não hemolítica com 28,3%. Quanto as reações tardias, totalizou 1,64%, sendo descritos três tipos de reações tardias no período, todas com baixa expressividade, sendo a aloimunização com 1,21%, outras reações tardias 0,25% e hemolítica tardia 0,18%. Como limitação do presente estudo, pode haver subnotificação de reações transfusionais, devido a não correlação de sinais apresentados por receptores, principalmente tardios, que possam ser associados à transfusão prévia. Conclusão: Os resultados obtidos com este estudo corroboram com os dados já descritos na literatura. Sabe-se que as reações podem ocorrer em decorrência de algum incidente do ciclo do sangue, ou do resultado inerente do processo. Portanto, a hemovigilância é a principal forma de garantir a segurança transfusional dos receptores com o registro e notificação dos eventos adversos, evitando-se a incidência de subnotificações. Sendo assim, é importante que as reações sejam identificadas corretamente e as condutas tomadas sejam adequadas, prevenindo-as através de equipes bem treinadas, processos bem definidos e qualidade dos hemocomponentes, a fim de manter a taxa de reações transfusionais conforme literatura.

Objetivo: Analisar a incidência de aloimunização em pacientes internados nos hospitais das agências transfusionais do país atendidas pela Grupo GSH. Material e métodos: Estudo retrospectivo realizado através do levantamento de dados obtidos do sistema informatizado no período de janeiro de 2021 a dezembro de 2023, os quais foram agrupados e tratados em planilha do programa Microsoft Excel. Os dados coletados incluíam sexo, idade e resultados de anticorpos eritrocitários detectados. Resultados: No período do estudo, foram registrados 62 casos de reações transfusionais classificadas como aloimunização, envolvendo a identificação de 86 anticorpos, dentre os quais pode-se observar a ocorrência da identificação em 23 casos (26,7%) do anticorpo anti-E e 14 casos (16,8%) identificados anti-Kell, seguidos de anti-Jka com 11 casos (12,8%), anti-c e anti-D com 7 casos cada ( 8,1%), anti-C 6 casos (7%), anti-M 5 casos (5,8%) e os demais anticorpos identificados que apresentaram baixa expressividade, que somados representam 13 casos (15,1%), sendo identificados: anti-Ch, anti-Dia, anti-Fya, anti-Jkb, anti-Lea, anti-Lua, anti-s, anticorpo frio. Quanto ao sexo dos receptores, 33 casos (53,2%) eram de receptores do sexo feminino e 29 casos do sexo masculino (46,8%). Quanto a idade, na distribuição por faixa etária observou-se 21 pacientes entre 61-75 anos (34%), 20 pacientes entre 46-60 anos (32,2%), 15 pacientes acima dos 75 anos (24,2%), 3 pacientes entre 16-30 anos (5%), 2 pacientes entre 0-15 anos (3,2%) e 1 paciente entre 31-45 anos (1,4%). Discussão: Ao analisar os dados, observou-se que a maior prevalência dos anticorpos identificados com 26,7% foi de anticorpos anti-E, 16,8% anti-K e 12,8% anti-Jka, os demais anticorpos identificados apresentaram baixa incidência variando de 1 e 7 casos, ficando entre 1,1% e 8,1%. A relação com o sexo dos receptores que aloimunizaram, após serem submetidos às transfusões tem-se a prevalência no sexo feminino (53,2%). As idades dos receptores variaram de 5 anos a 99 anos, com maior incidência na faixa etária de 61 a 75 anos, resultados estes que são correlacionadas as condições clínicas e laboratoriais dos receptores, que consequentemente acarretaram um maior número de transfusões com exposição maior a diferentes doadores. Conclusão: A Organização Mundial de Saúde (OMS) recomenda que o fornecimento de sangue seguro e adequado seja parte da política e infraestrutura de saúde de todos os países. Atualmente a transfusão de sangue é um recurso que salva vidas e melhora a saúde de quem se beneficia em diversas circunstâncias, porém pode resultar no desenvolvimento de aloanticorpos. Essa aloimunização predispõe o paciente ao risco de reações transfusionais hemolíticas tardias. Os anticorpos mais encontrados na aloimunização são dirigidos contra antígenos dos sistemas Rh e Kell, por serem estes considerados os mais imunogênicos. A identificação dos fenótipos eritrocitários dos grupos sanguíneos em pacientes e doadores de sangue, possibilita a classificação da frequência dos genes mais imunogênicos de cada sistema, sendo essencial para diminuir o risco de aloimunização, havendo a possiblidade do sangue compatível tornar a transfusão mais segura.

Abstract Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.

Introdução: A medicina transfusional é uma especialidade multidisciplinar responsável pela seleção e utilização adequada dos componentes do sangue. A solicitação de uma transfusão é considerada a partir da avaliação de parâmetros clínicos e laboratoriais, a fim de proporcionar melhores benefícios ao paciente receptor. Objetivo: Avaliar o perfil epidemiológico dos pacientes submetidos a transfusões de hemocomponentes internados em setores de terapia intensiva, em três hospitais no Estado de São Paulo: Atibaia, Santos e São José dos Campos. Método: Estudo descritivo retrospectivo. Avaliação das transfusões realizadas entre o período de fevereiro de 2022 a junho de 2023. Para o levantamento as transfusões foram classificadas quanto ao tipo de hemocomponente transfundido, diagnóstico, sexo e idade dos receptores. Resultados: No período do presente estudo foram transfundidos 7.332 hemocomponentes em 1.001 receptores nas unidades de terapia intensiva. Quanto aos hemocomponentes, foram transfundidos 3.631 concentrados de plaquetas (49,5%), 2.673 concentrados de hemácias (36,5%), 707 unidades de plasma fresco congelado (9,6%) e 321 unidades de crioprecipitado (4,4%). Observado 526 receptores do sexo masculino (52,5%) e 475 do sexo feminino (47,5%). Quanto a idade, na distribuição por faixa etária observou-se 383 pacientes entre 61‒75 anos (38,5%), 275 pacientes entre 76‒90 anos (27,5%), 180 pacientes entre 46-60 anos (18%), 89 pacientes entre 31‒45 anos (8,9%), 43 pacientes acima de 91 anos (4,3%) e 31 pacientes entre 16‒30 anos (3%). Foi avaliado também o diagnóstico sinalizado pelo médico no momento da prescrição. Observado maior frequência em Doenças onco-hematológicas com 39,36%, seguido por “Outros Diagnósticos” (25,33%), Anemias Sintomáticas (11,73%), Hemorragias e Sangramentos (10,57%), Cardiopatias (8,05%) e por fim as Neoplasias (4,96%). Discussão: Durante os 16 meses avaliados observou-se maior prevalência de solicitações de transfusão de concentrados de plaquetas, seguido pela transfusão de concentrados de hemácias, o que é esperado devido maior índice de transfusão em pacientes com Doenças Onco-hematológicas. Verificado a distribuição quase homogênea entre receptores do sexo masculino e feminino, com valores próximos de 50% entre ambos. Com relação à idade dos pacientes, a maior parte dos atendimentos foi de pacientes acima de 60 anos (aproximadamente 70% dos pacientes atendidos). A idade também está correlacionada ao diagnóstico, uma vez que temos uma maior prevalência de doenças onco-hematológicas em pacientes que já são idosos. Conclusão: O levantamento do perfil de pacientes atendidos, colabora com a manutenção dos estoques de hemocomponentes, pensando na quantidade e disponibilidade de bolsas especiais (irradiadas e fenotipadas), para manter na unidade, assim como no manejo de equipe técnica capacitada para atendimento das solicitações. Além disso, também auxilia no direcionamento estratégico das unidades para uma melhor gestão de recursos humanos e materiais.

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19–197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58–77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357–3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363–3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363–3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals. Plain language summary EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease. The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN. To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. The database provided clinical data of 398 patients with MPN incurring COVID-19: Patients were mostly elderly (median age was 69 years); Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN; Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19. Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted by Older age; Comorbidities; Exposure to immunosuppressive therapies. Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold by Older age; Comorbidities; Exposure to immunosuppressive therapies before the infection. In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.

Abstract Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value

Abstract In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.

Abstract Background Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose. Methods Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher’ exact test and the Mann–Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively. Results At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P

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Abstract. Invasive fungal diseases (IFDs) remain a major clinical issue in patients with hematological malignancies (HMs). To confirm the efficacy and safety of the new azole isavuconazole (ISV) in a clinical care setting, we planned a multicenter retrospective study; we collected data on all possible/probable/proven IFDs in patients with HMs treated with ISV in 17 centers. Between July 2016 and November 2018, 128 patients were enrolled, and 122 were fully evaluable. ISV was employed as the 1st line therapy in 43 (35%) patients and as a subsequent therapy in 79 (65%) patients. The response rate was 82/122 patients (67.2%); it was similar when using ISV as a 1st or 2nd line treatment (60.5% vs 70.9%, respectively; p = 0.24). In multivariate analysis, both female sex (OR: 2.992; CI: 1.22–7.34) and induction phase of treatment (OR: 3.953; CI: 1.085–14.403) were predictive of a favorable response. At a median follow-up of 5 months, 43 (35.2%) patients were dead; the 1-year overall survival (OS) was 49.9%. In multivariate analysis, the response to ISV (OR: 0.103; CI: 0.041–0.262) and IFD refractoriness to previous antifungals (OR: 3.413; CI: 1.318–8.838) were statistically significant for OS. Adverse events (AEs) were reported in 15/122 patients (12.3%); grade 3–4 AEs were reported in 5 (4%) and led to ISV discontinuation. Our study confirms the safety and tolerability of ISV, also in diseases other than acute leukemia. Phase of hematological disease, gender and refractoriness to previous antifungals are the main predictive factors for the aforementioned response and outcome.

MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL-expressing cells. We investigated whether MYB silencing modulates microRNA expression in Philadelphia-positive (Ph+) leukemia cells and if MYB-regulated microRNAs are important for the “MYB addiction” of these cells. Thirty-five microRNAs were modulated by MYB silencing in lymphoid and erythromyeloid chronic myeloid leukemia-blast crisis BV173 and K562 cells; 15 of these were concordantly modulated in both lines. We focused on the miR-17-92 cluster because of its oncogenic role in tumors and found that: i) it is a direct MYB target; ii) it partially rescued the impaired proliferation and enhanced apoptosis of MYB-silenced BV173 cells. Moreover, we identified FRZB, a Wnt/β-catenin pathway inhibitor, as a novel target of the miR-17-92 cluster. High expression of MYB in blast cells from 2 Ph+leukemia patients correlated positively with the miR-17-92 cluster and inversely with FRZB. This expression pattern was also observed in a microarray dataset of 122 Ph+acute lymphoblastic leukemias. In vivo experiments in NOD scid gamma mice injected with BV173 cells confirmed that FRZB functions as a Wnt/β-catenin inhibitor even as they failed to demonstrate that this pathway is important for BV173-dependent leukemogenesis. These studies illustrate the global effects of MYB expression on the microRNAs profile of Ph+cells and supports the concept that the “MYB addiction” of these cells is, in part, caused by modulation of microRNA-regulated pathways affecting cell proliferation and survival.

Kawasaki disease (KD) is an acute, self-limited, inflammatory disease affecting medium-sized arteries and particularly the coronary arteries in about 25% of untreated cases. KD is a clinical diagnosis based on the presence of ≥5 days of fever and the presence of ≥4 of the 5 principal clinical criteria. We described, for the first time to our knowledge, a case of a very early development (on day 1) of typical KD with transient coronary involvement, diagnosed on day 2 of disease and treated with aspirin and steroids on day 3, with complete resolution of clinical signs and coronary involvement.

This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD) at first evaluation in a emergency room. We found similar clinical features as duration of fever and number of KD criteria (p >0.5) but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p < 0.001). LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.

Translocation t(4;11)(q21;q23) leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11)(q21;q23)/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide.

Background Resistance to imatinib is an important clinical issue in the treatment of Philadelphia chromosome-positive leukemias which is being tackled by the development of new, more potent drugs, such as the dual Src/Abl tyrosine kinase inhibitors dasatinib and bosutinib and the imatinib analog nilotinib. In the current study we describe the design, synthesis and biological properties of an imatinib analog with a chlorine-substituted benzamide, namely compound 584 (cmp-584).Design and Methods To increase the potency, we rationally designed cmp-584, a compound with enhanced shape complementarity with the kinase domain of Abl. cmp-584 was synthesized and characterized in vitro against a panel of 67 serine/threonine and tyrosine kinases using radioactive and enzyme-linked immunosorbent kinase assays. We studied inhibitory cellular activity using Bcr/Abl-positive human cell lines, murine transfectants in proliferation experiments, and a murine xenotrans-planted model. Kinase assays on isolated Bcr/Abl protein were also performed. Finally, we used a wash-out approach on whole cells to study the binding kinetics of the inhibitor.Results cmp-584 showed potent anti-Abl activity both on recombinant protein (IC50: 8 nM) and in cell-based assays (IC50: 0.1–10 nM). The drug maintained inhibitory activity against platelet-derived growth factor receptors and c-KIT and was also active against Lyn (IC50: 301 nM). No other kinase of the panel was inhibited at nanomolar doses. cmp-584 was 20- to 300-fold more active than imatinib in cells. This superior activity was evident in intact cells, in which full-length Bcr-Abl is present. In vivo experiments confirmed the activity of cmp-584. Wash-out experiments showed that short exposure to the drug impaired cell proliferation and Bcr-Abl phosphorylation for a substantially longer period of time than imatinib.Conclusions The present results suggest a slower off-rate (dissociation rate) of cmp-584 compared to imatinib as an explanation for the increased cellular activity of the former.