Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by dysplasias, ineffective hematopoiesis and risk of acute myeloid leukemia transformation. Approximately 90% of MDS patients present mutations in genes involved in various cell signaling pathways. Specialized DNA polymerases, such as POLN, POLI, POLK, POLQ, POLH, POLL and REV3L, insert a nucleotide opposite replication–blocking DNA lesions in an error-prone manner and, in this way, sometimes can actively promote the generation of mutation. For the best of our knowledge, has not been described the mutations of these genes in MDS. DNA target sequencing CDS regions of the REV3L gene was performed in a 58-year-old man diagnosed as High Risk Myelodysplastic Syndrome. The patient presented very low hemoglobin, increased number of blasts, karyotype:47,XY,+8[6]/47,XY,del(7)(q32),+8[7], no response to hypomethylating therapy (decitabine), all markers of poor prognosis. Target sequencing identified a mutation c.9253-6T>C REV3L (Substitution - intronic) with VAF (variant allele frequency) = 16% considered pathogenic according to Functional Analysis through. Hidden Markov Models (FATHMM). This is the first evidence of REV3L mutation in MDS and, of utmost importance, associated with poor prognosis.

RESUMO A síndrome mielodisplásica (SMD) é uma desordem clonal das células-tronco hematopoiéticas caracterizada por citopenias periféricas devido à hematopoiese ineficaz e pelo aumento do risco de evolução para a leucemia mieloide aguda (LMA). As alterações cromossômicas representam o marcador mais importante da estratificação de risco para a transformação de LMA. Quebra das cromátides (chtb) é uma descontinuidade de uma única cromátide. Relatamos o caso de um paciente com SMD, cuja análise citogenética mostrou chtb espontâneo: 46,XY,add(13)(q34),chtb(15)(q24)[3]/47,XY,chtb(2)(q22),del(5) (q35),del(7)(q32),+8,del(11q)(q23),del(q22)[cp17]. O paciente foi considerado de alto risco devido ao cariótipo complexo e à presença de chtb. Sugerimos que essa anormalidade cromossômica possa ser considerada como marcador de instabilidade.

ABSTRACT Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by peripheral cytopenias due to ineffective erythropoiesis and an increased risk for evolving into acute myeloid leukemia (AML). Chromosomal abnormalities represent the most important marker of risk stratification for AML transformation. Chromatid break (chtb) is a discontinuity of a single chromatid. We report the case of a patient with MDS whose cytogenetic analysis showed spontaneous chromatid breakage (chrb): 46,XY,add(13)(q34),chtb(15)(q24) [3]/47,XY,chtb(2)(q22),del(5)(q35),del(7)(q32),+8,del(11q)(q23),del(q22)[cp17]. He was considered a high-risk patient due to the complex karyotype and the presence of chtb. We suggest that this chromosomal abnormality may be considered as a marker of genomic instability in MDS.

The aim this research is to develop a HS-SPME/GC-MS method to analyze the carbaryl in blood plasma samples of the rural workers, who live round the perimeter of Chapada do Apodi-CE. This was achieved by chromatographic signal of the 1-naftol, degradation product of carbaryl with the intention of evaluating the degree of exposure of the workers to pesticides, causing chromosome abnormalities as already evidence in appropriate literature. Three different types of covered SPME fibers were tested and a full factorial design with central point in two levels. The variables optimized were temperature and ionic strength and temperature was the response in the design. Study was undertaken to determinate the equilibrium time. The thermal degradation of carbaryl in SPME headspace was analyzed by 1H-NMR. Proposed method achieved low limits of detection and quantification (1.5 and 5 ng mL-1, respectively) with good precision and accuracy, using the method of weighted least squares. However, the proposed method can be considered a good alternative way of monitoring carbaryl in blood plasma by analytical signal of 1-naftol. None of the plasma analyzed presented a concentration of 1-naftol compound higher than limit of detection of the method proposed here.

O linfoma primário do osso (LPO) é uma condição extremamente rara, habitualmente confundida com outras lesões ósseas primárias. É responsável por cerca de 3%-5% de todos os tumores malignos no osso e 4%-7% de todos os linfomas nãoHodgkin extranodais. Caracteriza-se pelo envolvimento de um ou vários locais ósseos, com ou sem comprometimento de linfonodos regionais e vísceras. Histopatologicamente, o linfoma non Hodgkin de grandes células B representa a maioria dos casos de LPO. Ossos longos são mais frequentemente comprometidos, e o fêmur é o sítio mais acometido. Osso ilíaco e da coluna vertebral também podem ser atingidos. Relatamos um caso raro de linfoma não Hodgkin da vértebra em mulher de 41 anos. A imuno-histoquímica revelou CD20 e CD45 positivos. Ela foi diagnosticada com linfoma primário difuso de grandes células B da coluna vertebral. O estudo histopatológico da medula óssea não detectou infiltração por hemopatia linfoide. A paciente foi tratada com quimioterapia CHOP juntamente com etoposide, seguida de radioterapia (dose total = 3600cGy) na região tóraco-lombar. Não houve evidência de recidiva em um período de vinte meses de acompanhamento.

Primary bone lymphoma (PBL) is an extremely rare condition, commonly confused with other primary bone injuries. It accounts for approximately 3-5% of all malignant bone tumors and 4-7% of all extranodal non-Hodgkin's lymphomas. It is characterized by the involvement of one or multiple bone locations, with or without the involvement of regional lymph nodes and viscera. Histopathologically, diffuse large-B-cell lymphomas account for the majority of cases of PBL. Long bones are usually involved, with the femur being the most commonly affected site. Pelvic bones and the vertebral column can also be involved. We report on a rare case of PLB of the vertebra in a 41-year-old woman. Immunohistochemistry examinations revealed CD20 and CD45 positive cells. She was diagnosed with primary diffuse large B-cell lymphoma presenting as a vertebral column tumor. The histopathologic analysis of the bone marrow did not show lymphoproliferative disorders. The patient was treated with a CHOP plus etoposide regimen. Systemic chemotherapy was followed by radiotherapy (total dose = 3600 cGy) in the thoracolumbar region. There was no evidence of recurrence in the 20-month follow up.

O efeito leucemogênico dos agentes quimioterápicos após o tratamento para neoplasias é bem conhecido. Síndrome mielodisplásica secundária a quimio ou radioterapia, também denominada relacionada à terapia (SMD-t), geralmente ocorre quatro a sete anos após a exposição inicial ao agente quimio ou radioterápico, acomete habitualmente pacientes jovens, apresenta alta incidência de transformação para leucemia mielóide aguda (LMA), está associada a citopenias severas, displasia das três linhagens, celularidade medular reduzida e fibrose, e anormalidades citogenéticas em até 80% dos casos. As anormalidades mais freqüentes envolvem os cromossomos 5 e 7. No tocante à quimioterapia, os agentes alquilantes são as drogas mais comumente associadas com SMD-t. Quimioterápicos em altas doses usados como parte de regimes de condicionamento para transplantes de medula óssea e radioterapia, além dos esquemas COPP/ABV e BEACOPP, estão associados com SMD-t. Recentemente, drogas como azatioprina, cladribina e rituximab também foram relacionadas à SMD-t. Devido ao aumento da sobrevida de pacientes acometidos por neoplasias malignas, a SMD-t surge como efeito mutagênico desses tratamentos e confere prognóstico desfavorável.

The leukaemogenic effect of chemotherapeutic agents after treatment for other malignancies have been well described. Myelodysplastic syndrome secondary to chemo- and radiotherapy (MDS-t) usually develops four to seven years after the initial exposure to chemotherapy frequently involving young patients, shows a high incidence of transformation to AML, is associated with severe cytopenias, trilineage dysplasia, reduced marrow cellularity and fibrosis, and presents an incidence of chromosomal abnormalities of up to 80% of the cases. The most common abnormalities are related to chromosomes 5 and 7. Alkylating agents have been considered the most common drugs associated with MDS-t. High dose chemotherapy used as part of the conditioning regimen prior to bone marrow transplantation as well as traditional regimens such as COPP/ABV and BEACOPP have also been associated with MDS-t. Recently, drugs such as azathioprine, rituximab and cladribine have been reported as causes too. Due to the increasing survival of patients suffering from other malignancies, MDS-t results as a mutagenic effect of these therapies and is related to poor prognosis.

Gemtuzumab Ozogamicina (GO) é um derivado semi-sintético de caliqueamicina, um antibiótico citotóxico ligado a um anticorpo monoclonal direcionado contra antígeno CD33 presente nos mieloblastos leucêmicos. O objetivo deste trabalho é avaliar os efeitos colaterais, remissão e a sobrevida de 11 pacientes com leucemia mielóide aguda que utilizaram GO. A maior toxicidade foi atribuída à mielossupressão, a qual esteve presente em todos os pacientes. Um paciente foi a óbito devido a doença hepática veno-oclusiva. Quatro pacientes utilizaram a droga para tratamento de recaída e dois atingiram remissão parcial. Dois pacientes utilizaram a droga para tratamento de doença refratária e um atingiu remissão completa com 12 meses de sobrevida. GO foi utilizada para consolidação de cinco pacientes. Acreditamos que a droga é segura e pode ser uma opção para pacientes que não toleram os esquemas quimioterápicos tradicionais.

Gemtuzumab Ozogamicin consists of a semisynthetic derivate of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts. The aim of this report is to evaluate the side effects, remission and survival of 11 patients with acute myeloid leukemia that took Gemtuzumab Ozogamicin. The major toxicity was myelosuppression that was seen in all the patients. One patient died due to hepatic veno-occlusive disease. Four patients used the drug for relapse and two achieved partial remission. Two patients used the drug for refractory disease and one achieved complete remission with 12 months survival. Gemtuzumab Ozogamicin was also used for the consolidation therapy of 5 patients. We believe that Gemtuzumab Ozogamicin is safe and is an alternative for patients that do not respond to conventional therapy.

Gentuzumab Ozogamicina (GO) (Mylotarg®) tem como alvo células leucêmicas que expressam CD33 através de um anticorpo monoclonal conjugado a um agente citotóxico, a caliqueamicina. Esta droga foi aprovada para uso em pacientes idosos com leucemia mielóide aguda (LMA) recaída ou refratária e hepatotoxicidade é comum após sua administração. Tack e colaboradores apresentaram o primeiro caso de doença hepática veno-oclusiva (DHVO) após infusão de GO em um paciente que tinha realizado transplante de medula( TMO) há 8 meses. Três estudos de fase II com 188 pacientes com LMA foram analisados e a incidência de HVOD fatal foi inferior a 1%, sendo a realização de TMO o fator de risco mais importante. O objetivo deste artigo é relatar um caso raro de DHVO fatal com ruptura de veia e artéria hepática em um paciente de 68 anos que recebeu GO. Acreditamos que este é o primeiro relato de HVOD com ruptura de vasos hepáticos relacionado ao uso de GO.

Gemtuzumab Ozogamicin (Mylotarg®) targets leukemia cells expressing the CD 33 receptor by means of a monoclonal antibody conjugated to a cytotoxic agent, calicheamicin. It was approved for use in elderly patients with relapsed or refractory acute myeloid leukemia and reversible hepatotoxicity is common after administration. The first case of hepatic veno-occlusive disease was reported after Gemtuzumab Ozogamicin infusion in a patient who had been submitted to hematopoietic stem cell transplantation 8 months earlier. Three phase 2 studies with 188 patients with acute myeloid leukemia in first relapse that used Gemtuzumab Ozogamicin were analysed and the incidence of fatal hepatic veno-occlusive disease in these studies was < 1%, and prior hematopoietic stem cell transplantation was the most significant risk factor. The aim of this paper is to report a rare fatal case of hepatic veno-occlusive disease with rupture of the spleen vein and artery in a 68-year-old patient that had received Gemtuzumab Ozogamicin. To the best of our knowledge, it is the first case report of hepatic veno-occlusive disease with rupture of the spleen vein and artery related to Gemtuzumab Ozogamicin.