The effect of administration order of BU and CY on toxicity in hematopoietic SCT in humans

Universidade Federal de São Paulo, Div Bone Marrow Transplantat, São Paulo, BrazilUniversidade Federal de São Paulo, Div Bone Marrow Transplantat, São Paulo, BrazilWeb of Scienc

Acute promyelocytic leukemia: the study of t(15;17) translocation by fluorescent in situ hybridization, reverse transcriptase-polymerase chain reaction and cytogenetic techniques

Acute promyelocytic leukemia (AML M3) is a well-defined subtype of leukemia with specific and peculiar characteristics. Immediate identification of t(15;17) or the PML/RARA gene rearrangement is fundamental for treatment. The objective of the present study was to compare fluorescent in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and karyotyping in 18 samples (12 at diagnosis and 6 after treatment) from 13 AML M3 patients. Bone marrow samples were submitted to karyotype G-banding, FISH and RT-PCR. At diagnosis, cytogenetics was successful in 10 of 12 samples, 8 with t(15;17) and 2 without. FISH was positive in 11/12 cases (one had no cells for analysis) and positivity varied from 25 to 93% (mean: 56%). RT-PCR was done in 6/12 cases and all were positive. Four of 8 patients with t(15;17) presented positive RT-PCR as well as 2 without metaphases. The lack of RT-PCR results in the other samples was due to poor quality RNA. When the three tests were compared at diagnosis, karyotyping presented the translocation in 80% of the tested samples while FISH and RT-PCR showed the PML/RARA rearrangement in 100% of them. Of 6 samples evaluated after treatment, 3 showed a normal karyotype, 1 persistence of an abnormal clone and 2 no metaphases. FISH was negative in 4 samples studied and 2 had no material for analysis. RT-PCR was positive in 4 (2 of which showed negative FISH, indicating residual disease) and negative in 2. When the three tests were compared after treatment, they showed concordance in 2 of 6 samples or, when there were not enough cells for all tests, concordance between karyotype and RT-PCR in one. At remission, RT-PCR was the most sensitive test in detecting residual disease, as expected (positive in 4/6 samples). An incidence of about 40% of 5' breaks and 60% of 3' breaks, i.e., bcr3 and bcr1/bcr2, respectively, was observed.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Hematologia e HemoterapiaUNIFESP, EPM, Disciplina de Hematologia e HemoterapiaSciEL

Hematopoietic stem cells transplantation and acute myeloid leukemia: Brazilian guidelines

The objective of this work was to define guidelines for the indication of hematopoietic stem cells transplantation (HSCT) in the treatment of acute myeloid leukemia (AML) in Brazil. The role of HSCT in the treatment of AML was discussed by the authors and presented to the Brazilian Society of Bone Marrow Transplantation in a meeting to formulate and ratify the Brazilian Guidelines on HSCT. This consensus was based on a review of international publications and on the Brazilian experience in HSCT for the treatment of AML. The optimal treatment for AML in first complete remission (1CR) has not been defined yet. There is consensus on the indication of allogeneic HSCT with myeloablative conditioning for patients who present high risk cytogenetic changes. Allogeneic HSCT is not indicated for low cytogenetic risk 1RC patients and, apparently, allogeneic and autologous HSCT and consolidation chemotherapy are similar for intermediate risk patients.O objetivo deste trabalho foi definir diretrizes para a indicação do transplante de células-tronco hematopoéticas (TCTH) no tratamento da leucemia mieloide aguda (LMA) no Brasil. O papel do TCTH no tratamento da LMA foi discutido pelosautores e apresentado para a Sociedade Brasileira de Transplante de Medula Óssea na reunião sobre Diretrizes Brasileiras para o TCTH, que o ratificou. Este consenso foi baseado na revisão da literatura internacional e na experiência brasileira em TCTH para o tratamento da LMA. O tratamento ideal para leucemia mieloide aguda em primeira remissão completa (1RC) ainda não está definido. Há consenso na indicação do TCTH alogênico, com condicionamento mieloablativo, para pacientes que apresentem alterações citogenéticas consideradas de alto risco. O TCTH alogênico não está indicado na 1RC para pacientes de baixo risco citogenético e, aparentemente, o TCTH alogênico, autólogo ou a quimioterapia de consolidação são equivalentes para os pacientes de risco intermediário.Hospital de Clínicas de Porto Alegre Serviço de Hematologia e Transplante de Medula ÓsseaUniversidade de São Paulo Hospital das Clínicas Centro de Transplante de Medula ÓsseaHospital de Câncer de Barret HemonúcleoUniversidade Federal de São Paulo (UNIFESP) Hospital Israelita Albert Einstein Centro de Transplante de Medula ÓsseaAssociação de Combate ao Câncer em Goiás Hospital Araújo Jorge Serviço de Transplante de Medula ÓsseaHospital Israelita Albert Einstein Programa de Hematologia e Transplante de Medula ÓsseaUNIFESP, Hospital Israelita Albert Einstein Centro de Transplante de Medula ÓsseaSciEL

Hematopoietic Cell Transplantation as Curative Therapy for Idiopathic Myelofibrosis, Advanced Polycythemia Vera, and Essential Thrombocythemia

AbstractA total of 104 patients, aged 18 to 70 years, with a diagnosis of chronic idiopathic myelofibrosis (CIMF), polycythemia vera (PV), or essential thrombocythemia (ET) with marrow fibrosis were transplanted from allogeneic (56 related and 45 unrelated) or syngeneic (n = 3) donors. Busulfan (BU) or total body irradiation (TBI)-based myeloablative conditioning regimens were used in 95 patients, and a nonmyeloablative regimen of fludarabine plus TBI was used in 9 patients. The source of stem cells was bone marrow in 43 patients and peripheral blood in 61 patients. A total of 63 patients were alive at a follow-up of 1.3–15.2 years (median, 5.3 years), for an estimated 7-year actuarial survival rate of 61%. Eleven patients had recurrent/persistent disease, of whom 8 died. Nonrelapse mortality was 34% at 5 years. Patients conditioned with targeted BU (plasma levels 800–900 ng/mL) plus cyclophosphamide (tBUCY) had a higher probability of survival (68%) than other patients. Dupriez score, platelet count, patient age, and comorbidity score were statistically significantly associated with mortality in univariate models. In a multivariable regression model, use of tBUCY (P = .03), high platelet count at transplantation (P = .01 for PV/ET; P = .39 for other diagnoses), younger patient age (P = .04), and decreased comorbidity score (P = .03) remained statistically significant for improved survival. Our findings show that hematopoietic cell transplantation offers potentially curative treatment for patients with ICMF, PV, or ET

Reduced SLIT2 is Associated with Increased Cell Proliferation and Arsenic Trioxide Resistance in Acute Promyelocytic Leukemia

Simple Summary In solid tumors, the altered expression of embryonic genes such as the SLIT-ROBO family has been associated with poor prognosis, while little is known about their role in acute myeloid leukemia (AML). Previous studies reported frequent hypermethylation of SLIT2 mediated by the methyltransferase enzyme EZH2 and more recently the PML protein, which are commonly found to be aberrantly expressed in AML. Here, we aim to assess retrospectively the clinical relevance of the SLIT2 gene in acute promyelocytic leukemia, a homogenous subtype of AML. We demonstrated that reduced SLIT2 expression was associated with high leukocyte counts and reduced overall survival in different APL cohorts. STLI2 treatment decreased APL growth, while SLIT2 knockdown accelerated cell cycle progression and proliferation. Finally, reduced expression of SLIT2 in murine APL blasts resulted in fatal leukemia associated with increased leukocyte counts in vivo. These findings demonstrate that SLIT2 can be considered as a prognostic marker in APL, and a potential candidate for clinical studies of a more heterogeneous disease, such as AML. The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2(high) transcript levels were associated with cell cycle arrest, while SLIT2(low) APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92-0.97; p <0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated

Projeto ONCO: preparo odontológico para pacientes portadores de neoplasias malignas

Introdução: É esperado que pacientes com câncer desenvolvam algum tipo de complicação na região oral, que pode estar relacionada às condições de saúde bucal do paciente e ao tipo de terapia utilizada. É de grande importância que o profissional da odontologia conheça as modalidades de tratamento do câncer de boca para o preparo da cavidade bucal antes, durante e após a terapia. Objetivos: O objetivo do projeto é possibilitar a formação de profissionais qualificados e competentes para atender adequadamente a pacientes portadores de neoplasias malignas, no pré e pós-operatório, no pré ou pós- tratamento de radioterapia e/ou quimioterapia, bem como, pesquisar, inovar e desenvolver novos protocolos, técnicas e metodologias, correlacionando as alterações clínicas com as características sistêmicas, dentro de um enfoque multidisciplinar e multiprofissional. Métodos: O projeto Onco atendeu mais de 200 pacientes oncológicos, realizando mais de 600 procedimentos, entre exodontias, dentística restauradora, endodontia, biopsias e cirurgias oncológicas em lábio, língua e mucosa oral com expectativas de cura. Acompanhamos e controlamos pacientes que desenvolveram osteoradionecrose e osteoradiomielite de mandíbula, pós- radioterapia, e proservação dos cânceres de cirurgia de cabeça e pescoço, operados e diagnosticados neste serviço. Resultados: O Projeto Onco vem se desenvolvendo de maneira excepcional, tendo sido procurado, por Hospitais Oncológicos, tais como, o Instituto de Oncologia e Radioterapia do Vale do Paraíba e pelo serviço de Transplante de Medula Óssea do Hospital Pio XII, para ser sua referência nos tratamentos odontológicos. Já hoje, desenvolvemos atendimento odontológico de alto nível para pacientes oncológicos e transplantados, cujo campo de atuação é extremamente carente em todo o país

Projeto ONCO: preparo odontológico para pacientes portadores de neoplasias malignas

Introdução: É esperado que pacientes com câncer desenvolvam algum tipo de complicação na região oral, que pode estar relacionada às condições de saúde bucal do paciente e ao tipo de terapia utilizada. É de grande importância que o profissional da odontologia conheça as modalidades de tratamento do câncer de boca para o preparo da cavidade bucal antes, durante e após a terapia. Objetivos: O objetivo do projeto é possibilitar a formação de profissionais qualificados e competentes para atender adequadamente a pacientes portadores de neoplasias malignas, no pré e pós-operatório, no pré ou pós- tratamento de radioterapia e/ou quimioterapia, bem como, pesquisar, inovar e desenvolver novos protocolos, técnicas e metodologias, correlacionando as alterações clínicas com as características sistêmicas, dentro de um enfoque multidisciplinar e multiprofissional. Métodos: O projeto Onco atendeu mais de 200 pacientes oncológicos, realizando mais de 600 procedimentos, entre exodontias, dentística restauradora, endodontia, biopsias e cirurgias oncológicas em lábio, língua e mucosa oral com expectativas de cura. Acompanhamos e controlamos pacientes que desenvolveram osteoradionecrose e osteoradiomielite de mandíbula, pós- radioterapia, e proservação dos cânceres de cirurgia de cabeça e pescoço, operados e diagnosticados neste serviço. Resultados: O Projeto Onco vem se desenvolvendo de maneira excepcional, tendo sido procurado, por Hospitais Oncológicos, tais como, o Instituto de Oncologia e Radioterapia do Vale do Paraíba e pelo serviço de Transplante de Medula Óssea do Hospital Pio XII, para ser sua referência nos tratamentos odontológicos. Já hoje, desenvolvemos atendimento odontológico de alto nível para pacientes oncológicos e transplantados, cujo campo de atuação é extremamente carente em todo o país