B-lymphoblastic leukemia/lymphoma associated with t(8;13)(p11;q12)/ ZMYM2 (ZNF198)-FGFR1 : rare case and review of the literature.

Myeloid and lymphoid neoplasms with fibroblastic growth factor receptor-1 (FGFR1) abnormalities originate from mutated pluripotent stem cells and have a heterogeneous clinical presentation. There are 12 identified partner genes commonly involved in FGFR1 translocation at an 8p11 breakpoint. In FGFR1-related neoplasms, T-lymphoblastic lymphoma with eosinophilia is the most common clinical scenario, whereas acute B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare. To date, only 7 cases of B-ALL/LBL with FGFR1 abnormalities have been reported. Here, we report an additional case of a 64-year-old gentleman with leukocytosis, eosinophilia and diffuse mediastinal and general lymphadenopathy. Bone marrow examination showed patchy infiltrates of immature precursors/blasts, along with myeloid/eosinophilic hyperplasia. Immunophenotyping confirmed increased B lymphoblasts (30-40%). Karyotyping revealed cytogenetic abnormalities, including t(8;13)(p11;q12)/ZMYM2 (ZNF198)-FGFR1 and trisomy 21. The patient did not respond to hyper-CVAD chemotherapy and within 4 months developed acute myelomonocytic leukemia and expired 11 months after the initial diagnosis. Similar cases from the literature are reviewed.

Systemic therapy for advanced hepatocellular carcinoma: past, present, and future.

BACKGROUND: Although approximately 80% of hepatocellular carcinoma (HCC) cases occur in developing countries, the incidence of HCC in Western countries is on the rise due to the impact of hepatitis C. Challenges in developing effective therapies include the inherent chemoresistance of HCC, the pharmacologic challenges presented by a diseased liver, the presentation of most patients at advanced stages, and the difficulty in adequately measuring radiological response. While responses to traditional chemotherapeutic agents have been documented, significant survival benefit is debatable. METHODS: The authors review the results of published clinical trials of systemic therapy and immunotherapy that have impacted the present treatment of HCC. RESULTS: With recent progress in the elucidation of HCC molecular pathways, targeted agents show promise. The multikinase inhibitor sorafenib has provided survival benefit in patients with advanced HCC and well-preserved liver function. Sunitinib, bevacizumab, epidermal growth factor receptor inhibitors, and mammalian target of rapamycin (mTOR) inhibitors have shown activity in small patient cohorts. Immunotherapy appears to be a promising approach that can result in the regression of bulky, invasive cancer in some patients. CONCLUSIONS: New agents with a variety of mechanisms of activity offer promising therapeutic options for patients with advanced HCC.

Nitrogen availability in an apple orchard with weed management / Disponibilidade de nitrogênio em solo de pomares de macieira com manejo de plantas espontâneas

ABSTRACT: Weed management in apple orchards (Malus domestica) can affect the leaching of nitrogen (N) in soil. The study aimed to evaluate the potential leaching of N forms in soil of an apple orchard with different weed management treatments. The experiment was conducted in an apple orchard implanted in 2008. In October 2011, 80 plants were selected and the following treatments were implemented: no weed management (NM), desiccation of weeds on the tree row with herbicide use (DR) and mechanical mowing of weeds on the tree row (MR). Yield was evaluated in the 2011/2012, 2012/2013 and 2013/2014 crop seasons. In May 2012 porous cup lysimeters were installed in the NM, DR and MR treatments. In the solution collected at 0.20m, NH4 +-N and NO3 --N were analyzed sixteen times and mineral N concentration was calculated. The highest concentrations of NO3 --N and mineral N occurred in soil solution with DR, which increases availability of the nutrient to apple trees, but also enhances the potential losses. Weed management and N flow in the solution did not affect apple yield.

RESUMO: O manejo de plantas espontâneas em pomares de macieira (Malus domestica) pode afetar a lixiviação de nitrogênio (N) do solo. O trabalho objetivou avaliar a lixiviação de formas de N em solo sob pomar de macieiras com diferentes manejos de plantas espontâneas. O experimento foi conduzido em um pomar de macieira implantado em 2008. Em outubro de 2011, foram selecionadas 80 plantas e implantados os tratamentos: sem manejo das plantas espontâneas (SM); dessecamento das plantas espontâneas na linha de plantio com uso de herbicidas (DL) e roçada mecânica das plantas espontâneas na linha de plantio (RL). Nas safras 2011/2012, 2012/2013 e 2013/2014 foi avaliada a produtividade. Em maio de 2012 foram instalados lisímetros com cápsula porosa nos tratamentos SM, DL e RL; e na solução coletada a 0,20m em dezesseis épocas foram analisados NH4 +-N e NO3 --N, e calculado o teor de N-mineral. Os maiores teores de NO3 --N e mineral-N ocorreram na solução no solo com DL, o que aumenta a disponibilidade do nutriente às macieiras, mas também potencializa as perdas. O manejo de plantas espontâneas e o fluxo de N na solução não afetaram a produtividade de maçã.

Base de datos sistematizada de historias clínicas pertenecientes al I. I. HEMA: informe preliminar / Systematized database of medical records belonging to I. I. HEMA: preliminary report

Se procedió a confeccionar una base de datos de los casos atendidos en Clínica Hematológica del Instituto de Investigaciones Hematológicas. Se registró información sobre: a) Datos demográficos; b) Enfermedad actual; c) Métodos diagnósticos y d) Clasificación de las enfermedades según CIE 10. Sobre un total de 3573 casos registrados entre junio de 2002 y noviembre 2015 se analizaron 1300 (42%) casos. Los principales resultados muestran un predominio de las anemias, y entre ellas las ferropénicas. El mielograma y el frotis de sangre periférica predominaron entre los procedimientos diagnósticos. El tiempo entre primera consulta y diagnóstico muestra que en la mayoría (79,24%) de los casos este fue menor a 3 meses. En un 55,9 % de los casos se inició tratamiento antes del mes. (AU)

A data base was made from cases treated in the Hematological Clinic service. The following information was recorded: a) Demographics; b) Current disease; c) Diagnostic methods and d) Disease classification according to CIE 10. There were analyzed 1300 (42%) out of 3573 cases between June 2002 and November 2015. The main results show predominance of anemia and among them iron deficiency. The myelogram and peripheral blood smear predominated among the diagnostic procedures. Time between first consultation and diagnosis shows that in the majority (79.24%) of cases was less than 3 months. In 55.9% of cases it started treatment before the month. (AU)

Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma: a single institutional experience and literature review.

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder. HIV-negative PBL has not been extensively reported. Nine HIV-negative PBL patients evaluated at Moffitt Cancer Center were studied. Eight patients had extranodal diseases. All patients were treated with CHOP or hyper-CVAD. Responses were observed in 8 cases (7 complete, 1 partial responses). Four patients underwent consolidation with autologous hematopoietic stem cell transplant (HSCT) in first complete remission (CR1). At median follow-up of 23.9 months, 7 patients were alive and 5 were disease-free. Aggressive induction chemotherapy and consolidation with autologous HSCT in CR1 might be considered for patients with HIV-negative PBL.

Perdas de nitrogênio do solo e resposta do pessegueiro à adição de composto orgânico / Loss of soil nitrogen and peach yield with the addition of organic compost

A aplicação de composto orgânico no solo pode incrementar a produção de pêssego, porém parte do N pode ser perdido por lixiviação e volatilização. O trabalho objetivou avaliar o estado nutricional das plantas, a produção de pêssego, a lixiviação de formas de N no solo e a volatilização de N-NH3 em um pomar de pessegueiro com a adição de composto orgânico produzido a partir de resíduos de agroindústrias de suco, resíduos de abatedouro de aves e serragem. O pomar foi implantado em 2009 e, em julho de 2010, 2011 e 2012, foram aplicados 0, 3, 6, 12 e 24L de composto por m2 e avaliaram-se os teores totais de nutrientes nas folhas e a produção. Em 2012, usando lisímetros instalados a 20 e a 40cm de profundidade, avaliaram-se as formas de N lixiviadas na solução percolada nos tratamentos 0 e 24L de composto. Usando câmeras coletoras, foi avaliada a volatilização de N-NH3 em todos os tratamentos até 478h depois da deposição do composto no solo. A aplicação de composto na superfície do solo incrementou o teor de K e N nas folhas completas, aumentando a produção de frutos. A aplicação de composto no florescimento aumentou a concentração de nitrato na solução do solo, somente na profundidade de 20cm. A emissão de amônia aumentou com o incremento da dose de composto aplicado, especialmente e nos períodos de maior temperatura.

The application of organic compost to the soil can increase the production of peach, although part of the N may be lost by leaching and volatilization. The aim of this study was to evaluate the nutritional status, yield of peaches, leaching of N forms and volatilization of NH3-N in a peach orchard with the addition of compost produced from agroindustrial juice waste, poultry slaughterhouse residues and sawdust. The orchard was established in 2009, and in july 2010, 2011 and 2012 the quantities of 0, 3, 6, 12 and 24L of organic compost per m2 were applied on a peach orchard and the total nutrient content in leaves and production was evaluated. In 2012, using lysimeters installed at 20 and 40cm deep in the soil, it was measured the forms of N in the solution in the treatments of 0 and 24L of compost. The volatilization of NH3-N was assessed in all the treatments up to 478h after compost application on the soil. The application of compost on the soil surface increased the content of K and N in whole leaves, increasing fruit production. The compost application at flowering increased the concentration of nitrate in the soil solution at a depth of only 20cm. The ammonia emission increased especially with the augmenting dose of compost applied, and in periods of higher temperature.

Produção e nitrogênio no solo e na solução em pomar demacieira submetido à aplicação de fontes de nutrientes / Yield and nitrogen in soil and solution in an appleorchard subjected to application of nutrient sources

A aplicação de fontes de nitrogênio (N) em pomar de macieira pode incrementar o teor do nutriente no solo ao longo do ciclo, afetar o estado nutricional e a produção, mas parte do N pode ser perdido por lixiviação. O trabalho objetivou avaliar o teor de N total em folhas, a produção e o fluxo de N no solo e na solução, em um pomar de macieira com a aplicação de distintas fontes de N, em um experimento em Urubici (SC). Plantas foram selecionadas, receberam a aplicação de ureia (U), ureia peletizada (UP) e cama sobreposta de suínos (CS); além de um tratamento sem adubação (SA). Nas safras 2011/2012 e 2012/2013 foram analisados teores de N em folhas completas e mensurados o crescimento das plantas e a produção de frutos. Foram coletadas amostras de solo e de solução, e analisados os teores de N-NH4 + e N-NO3 - ao longo da segunda safra. Aplicações de U, UP e CS aumentaram o rendimento da macieira no segundo ano, mas o teor de N em folhas não foi afetado nas duas safras. A aplicação de N afetou o fluxo de formas do nutriente no solo e na solução ao longo do ciclo da cultura, com pequenos incrementos nos teores do solo e da solução em períodos próximos à aplicação das diferentes fontes de N.

The application of nitrogen (N), from different sources, in apple orchard can increase soil N content, affecting the plant's nutritional status and yield, but part of the N can be lost by leaching. With the aim of assessing plant nutritional status and yield, and N flow in the soil and solution an experiment was carried out in in an apple orchard in Southern Brazil, applying different N source. Selected plants received the following treatments: application of urea, pelletized urea or pig deep litter, besides a control without fertilization. In the 2011/2012 and 2012/2013 crop seasons, N contents in whole leaves were analyzed and plant growth and fruit yield parameters were measured. Soil and soil solution samples were collected and the NH4 +-N and NO3 --N contents were analyzed during the second crop season. Application of pig deep litter, urea and pelletized urea increased apple yield in the second crop season, with no differences among treatments in leaf total N content at any time period. The application of N to the soil affected the flow of nutrient forms in the soil and in the solution throughout the apple crop cycle, with small increases in soil and in solution contents in periods near the application of the different N sources to the soil.

Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolution.

We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.2;p11.2), was found. Both rearrangements were confirmed by FISH. Molecular cytogenetics analysis using p53 probe showed monoallelic loss of this tumor suppressor gene in 43.8% and 77.3% of cells for the first and the second studies, respectively). In both studies, deletions of D13S319 (18% and 12% of cells) and D13S25 loci (13% and 12% of cells) at 13q14 were found. Polymerase chain reaction analysis showed the MBR/JH rearrangement of the bcl-2 gene. FISH studies using LSI bcl-2/IgH probe allowed quantifying the clonal cell population with this rearrangement (4% and 6.6% of cells at diagnosis and RT, respectively). To our knowledge, this is the first case with a psu dic(12,21) described in B-CLL. The low percentage of cells with the 13q14 deletion and bcl-2/IgH rearrangement suggests that they were secondary events that resulted from clonal evolution. Our patient had a short survival (9 months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression.

Linfomas No Hodgkin clínicamente agresivos: recientes desarrollos / Aggressive Non-Hodking's lymphoma: an update on new developments

Los linfomas agresivos constituyen un grupo importante (apróximadamente 40 por ciento) dentro de las neoplasias linfoides malignas. Los estudios epidemiólogicos indican un marcado aumento en la incidencia de los linfomas en las últimas 3 décadas, pero su causa no se conoce bien. La clasificación de los linfomas ha sido recientemente revisada por las actuales clasificaciones REAL (Revised European American Lymphoma Project) y de la Organización Mundial de la Salud (WHO). Los nuevos descubrimientos en aspectos moleculares prometen ahondar el conocimiento biológico y eventualmente modificar la terapéutica de los linfomas. El tratamiento standard CHOP (Ciclofosfamida, Hidroxidaunomicina o Adriamicina, Oncovin o Vincristina y Prednisona) no ha podido ser superado por regímenes de drogas más complejas y agresivas. El trasplante de médula ósea constituye una alternativa terapéutica efectiva en pacientes seleccionados.

Tratamiento del mieloma múltiple refractario o en recaída con mitoxantrona y altas dosis de dexametasona: estudio del mecanismo de resistencia a drogas inducido por glicoproteina-P 170 / Treatment refractory multiple myeloma or in relapse with mitoxantrone and high doses dexamethasone a study of the mechanism of drug resistence induced by P-glycoprotein 170

Treatment of refractory or relapsed multiple myeloma withmitoxantrone and high dose dexamethasone. Study of the mechanism of drug resistance induced by p-glycoprotein 170. One of the most studied mechanism of drug resistance is the induction of a gene (MDR) codifying for a protein (gp-170), which acts by decreasing the intracellular accumulation of various citotoxic drugs. The mechanisms of resistance for mitoxantrone are not yet well understood. As the prognosis of patients with multiple myeloma not responding initially to chemotherapy, or relapsing after achieving a response, is generally poor, the purpose of the present study is to evaluate the activity of mitoxantrone in refractory or relapsed multiple myeloma, as well as to study the ability of this agent to induce drug resistance through the mechanism of p-glycoprotein. Patients will be studied before and at the end of therapy for the expression of p-glycoprotein. Chemotherapy consists of mitoxantrone 12 mg/m²iv, day 1 plus dexamethasone 40 mg iv, daily for 4 days, in six monthly cycles.

CAVPE-Interferón: en linfomas No Hodgkin de bajo grado / CAVPE-Interferon: in low-grade lymphoma, Non-Hodgkins

El protocolo 7-LBG-87 que evalúa el tratamiento con poliquimioterapia (CAVPE), más radioterapia en áreas residuales, más mantenimiento con alfa interferón en pacientes (pts) con Linfoma No Hodgkin de bajo grado (LNH-BG) de mal pronóstico y sólo el seguimiento sin tratamiento hasta su progresión en aquellos pacientes de buen pronóstico, se inició en julio de 1987. Hasta abril de 1993, ingresaron 93 pacientes evaluables, 40 por ciento de los pacientes observados inicialmente, han requerido tratamiento. De ellos, el 58 por ciento obtuvo remisión completa. De los 58 pts que requirieron quimioterapia al diagnóstico, el 60 por ciento (35) obtuvo remisión completa y 15 pts remisión parcial. En la mayoría de los pts que obtuvo remisión parcial, la misma estuvo relacionada con la presistencia de infiltrados linfoides en la médula ósea. La duración actuarial de la remisión completa, muestra que el 55 por ciento de los pts en quimioterapia estarán en remisión completa a 40 meses, versus el 18 por ciento de aquellos tratados a la progresión (NS). El tiempo hasta la progresión en el primer grupo es de 38 por ciento versus 18 por ciento en el grupo de observación (NS). Se vió una tendencia a una mejor sobrevida en el grupo de quimioterapia inicial (63 por ciento ) versus el de observación (30 por ciento ) sugiriendo que la quimioterapia podría beneficiar a dichos pts si se emplean temporariamente. Se requerirá un tiempo más prolongado de observación, dada la característica indolente de esta enfermedad