Yes / The project was designed as a retrospective service evaluation using audit to assess the identification and documentation of red flags in initial assessment of patients with low back pain. Firstly, the documentation of 11 predetermined red flags was assessed. Secondly, the documentation of relevant additional information was assessed and finally, compliance with local policy to highlight positive red flag findings in the designated area on the paperwork was examined. The documentation for the majority of red flags was high, however, clear gaps were identified. Additionally, there was no evidence of further clinical consideration of positive red flags during the diagnostic process. Possible factors influencing red flag documentation are discussed and suggestions are provided to improve recording and response to clinical indicators of malignancy.

This study aimed to understand how the identity of Manitobans with early malignancy is affected through diagnosis, decision making and treatment. Using grounded-theory methodology, semi-structured interviews were conducted with 18 adult patients with early breast, colon, lung, prostate and gynecological cancers, before and after adjuvant treatment decision making. 15 adult friends and family members were also interviewed. Significant findings include: 1) After diagnosis, the “cancer identity” emerged as a new aspect of the patient’s identity; 2) Establishing a post-diagnosis routine was a significant source of distress for patients; 3) Ability to re-establish routine post-diagnosis may be enhanced by providing earlier notification of medical appointment times and information regarding how different treatment options will affect the patient’s identity. This study provides new insight into the experience of patients with malignancy in Manitoba. Additionally, it presents recommendations, based on the insights and concerns of its participants, for improving the cancer journey of Manitobans. / May 2017

Gastrointestinal symptoms have a prevalence of 20-40% in the general adult population in the Western world. These symptoms are generally considered to be poor predictors of organic findings [e.g. peptic ulcer disease (PUD) or malignancy]. Approximately 50% of patients seeking care for such symptoms have no organic explanation for these upon investigation. When other organic or other functional conditions are excluded [e.g. PUD, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS)] the remaining patients are labelled as having functional dyspepsia (persistent or recurrent pain and/or discomfort centred in the upper abdomen). Management of functional dyspepsia remains a challenge, reflecting the heterogeneity of the patients and the uncertain role of drug treatment. Also, prognostic factors for treatment success are largely unknown. I have therefore performed a series of studies to shed light on these issues: The first study (Paper I) was performed in a randomly selected adult population (n=1,001) assessing upper and lower gastrointestinal symptoms at two occasions with 1 to 6 month intervals. The results show that gastrointestinal symptoms are common (57%) and fluctuate to some extent in the shorter term. Troublesome dyspeptic symptoms remain in two out of three individuals. This proportion was similar whether or not organic findings were present. In the second study (Paper II) 799 patients with dyspeptic symptoms were evaluated with regard to whether gastrointestinal symptoms, identified by self-administered questionnaires, correlate with endoscopic diagnoses and discriminate organic from non-organic (functional) dyspepsia. The impact of dyspeptic symptoms on health-related well-being was also evaluated. Approximately 50% of these dyspeptic patients were found to have functional dyspepsia at upper endoscopy. A difference was discovered in the symptom profile between patients with organic and functional dyspepsia. Predicting factors for functional dyspepsia were found. This study shows that use of self-administered symptom questionnaires may aid in clinical decision making for patient management, e.g. by reducing the number of endoscopies, although probabilities of risks for organic dyspepsia are difficult to transfer to management of the individual patient. The results also indicate that the health-related well-being in patients with functional and organic dyspepsia is impaired to the same extent, illustrating the need for effective treatment of patients with functional dyspepsia, a group not well served by currently available treatment modalities. The aim of the third study (Paper III) was to develop and evaluate a selfadministered questionnaire focusing on upper abdominal and reflux complaints to allow for identification of patients with heartburn and factors that might predict symptom relief with omeprazole both in GERD and functional dyspepsia patients. The diagnostic validity of the questionnaire was tested against endoscopy and 24-hour pH monitoring. The questionnaire had a sensitivity of 92%, but a low specificity of 19%. Symptom relief by omeprazole was best predicted by the presence of predominant heartburn described as ‘a burning feeling rising from the stomach or lower chest up towards the neck’ and ‘relief from antacids’. These results indicate that this questionnaire which used descriptive language, appeared to be useful in identifying heartburn and predicting responses to omeprazole in patients with upper gastrointestinal symptoms. The fourth study (Paper IV) was a pilot study investigating the symptom response to omeprazole 20 mg twice daily or placebo for a duration of 14 days in 197 patients with functional dyspepsia. We concluded that a subset of patients with functional dyspepsia, with or without heartburn, would respond to therapy with omeprazole. In the final study (Paper V) the aim was to identify prognostic factors for the treatment success to a 4-week course of omeprazole 10 or 20 mg once daily in 826 patients with functional dyspepsia. The most highly discriminating predictor of treatment success was the number of days without dyspeptic symptoms during the first week of treatment. Fewer days with symptoms during the first week indicated higher response rates at four weeks. In addition, positive predictors of treatment response to omeprazole were identified as age >40 years, bothersome heartburn, low scores of bloating and diarrhoea, history of symptoms for <3 months and low impairment of vitality at baseline. The results indicate that early response during the first week to treatment with a proton pump inhibitor seems to predict treatment success after four weeks in patients with functional dyspepsia. Conclusion: These studies have shown that a large proportion of adult individuals in society, both those who seek and those who do not seek medical care, suffer from symptoms located in the upper part of the abdomen regardless of whether an organic cause is present. A subset of patients without organic findings and other functional conditions, i.e. functional dyspepsia, respond to therapy with omeprazole irrespective of the presence or absence of heartburn . An excellent way to predict the response to a full course of omeprazole in functional dyspepsia is to assess the early response (first week) to treatment. These findings allow for better and faster targeting of acid inhibitory therapy in functional dyspepsia, which potentially can result in more effective clinical management of these patients and savings of health care resources.

The objectives of this research were to test treatment and survival differences between women and men with lung cancer as there is minimal investigation in the literature. Three research questions were developed with statistical testing for gender differences based on similar cancer type, stage, treatment assignment and survival. Data for 44,863 primary lung cancer cases were collected from eight U.S. state-based cancer registries to investigate the research questions. The lung cancer incidence data included the morphological cell-types of adenocarcinoma (AC); squamous cell carcinoma (SCC); large cell carcinoma (LCC) and small cell carcinoma (SCC). Stage, grade, treatment type, as well as, individual characteristics such as gender, age at diagnosis, marital status at diagnosis and race were other variables obtained to be included in the statistical models. Reporting the overall effect for lung cancer gender specific treatment differences or survival has not been demonstrated in the literature to the author's knowledge. By convention, main effects and interaction effects are reported in the literature; without including an evaluation the overall effect of a variable on the outcome, possible misinterpretations could be made. For example, utilizing the Cox's Proportional Hazards model when the interaction effect of gender and treatment type received was examined, females were at an increased risk for death by as much 29% as compared to males (HR = 1.18, 95% CI 1.09 - 1.29). But when the gender effect on survival was assessed, there was an increase in females survivorship as compared to males by as much as 28% (HR = 0.80, 95% CI 0.72 - 0.97 ). In conclusion, by using a unique statistical approach, statistically significant Odds Ratios and Hazard Ratios were demonstrated for the research data set when the overall interaction effect on the outcome was examined. Recommendations to health care practitioners include adhering to current guidelines, e.g. American Medical Association, for lung cancer treatments. Standard treatment protocols were not always followed for early stage disease, e.g. females versus males with stage I lung cancer were 1.71 times more likely to receive chemotherapy in combination with radiation therapy versus a standard first treatment course of surgery (OR = 1.71, 95% CI 1.06 - 2.78). Also, depending on the lung cancer morphology and lung cancer treatment, females as compared to males could exhibit an increase in survivorship by as much as 28%. To improve the results of medical care decisions for lung cancer, clinicians may find the information presented in this study useful and encourage further research on which treatment increases survival for both men and women.

The lymphoid tissues consist of distinct cell subpopulations of B and T cell lineages and possess complex signaling pathways that are controlled by a myriad of molecular interactions. During the fine-tuned developmental process of the lymphoid system, inappropriate activation of oncogenes and loss of tumor suppressor gene activity can push lymphocytes into uncontrolled clonal expansion, causing several lymphoid malignancies. V(D)J recombination is one such essential process, important for the proper development of the mammalian immune system. However, mistakes in normal V(D)J recombination can lead to deletion of tumor suppressor genes or activation of proto-oncogenes. In the first part of the study, the physiological and pathological roles of DNA binding domain of RAG1 have been characterized. RAG (Recombination Activating Gene) complex consisting of RAG1 and RAG2, is a site specific endonuclease responsible for the generation of antigen receptor diversity. It cleaves a specific DNA sequence termed as recombination signal sequence (RSS), comprising of a conserved heptamer and nonamer. Recent studies have shown that RAGs can also act as a structure-specific nuclease by cleaving flaps, heterologous loops, bubbles, hairpins etc. Nonamer binding domain (NBD) of RAG1 plays a central role in the recognition of RSS during its sequence specific activity. To investigate its DNA binding properties, NBD of murine RAG1 was cloned, overexpressed and purified from E. coli. Electrophoretic mobility shift assays showed that NBD binds with high affinity to nonamer in the context of 12/23 RSS. However, it did not bind to heteroduplex DNA, irrespective of the sequence of the single-stranded region. Interestingly, when a nonamer was present next to a heteroduplex DNA, NBD exhibited robust binding. NBD binding was specific to thymines when single stranded DNA containing poly A, C, G and T were used. Biolayer interferometry studies showed that the observed poly T binding to NBD was robust with a binding constant of 0.45±0.16 µM. >23 nt was essential for NBD binding at homothymidine stretches. On a double-stranded DNA, NBD could bind to A:T stretches, but not G:C stretches or random sequences. Although NBD is indispensable for sequence-specific activity of RAGs, external supplementation of purified nonamer binding domain to NBD deleted cRAG1/cRAG2 did not restore the sequence specific activity, suggesting that the overall domain architecture of RAG1 is important for maintaining its properties. Therefore, we define the sequence requirements of NBD binding to double- and single-stranded DNA, which will have implications in generation of chromosomal rearrangement and genomic instability in lymphoid cells. Genetic alterations are one of the hallmarks of lymphoid malignancies. Many genes involved in chromosomal abnormalities are known to play central roles in the development of normal lymphocytes. In the second part of the study, molecular mechanism associated with fragility of the transcription factor, B cell leukemia 11B (BCL11B) that drives malignant transformation of T-cells has been studied. BCL11B is a zinc finger protein transcription factor with multiple functions. It plays a key role in both development and subsequent maintenance of T-cells. BCL11B gene alterations are implicated in a number of diseases including T-cell malignancies. It acts as a haplo-insufficient tumor suppressor and loss of BCL11B allele leads to susceptibility to mouse thymic lymphoma and human T-ALL. Recent studies reveal heterozygous BCL11B mutations and deletions across each of the major molecular subtypes of T-ALL (15% of patients). Most of the BCL11B missense mutations identified so far affected the residues within BCL11B zinc finger domains of the exon 4. However, mechanism of generation of such specific mutations leading to altered functions of BCL11B remains to be explored. In the present study, we address the potential mechanism of fragility of BCL11B gene during leukemia genesis. Firstly, we have evaluated different regions of BCL11B gene for presence of non-B DNA sequence motifs. Studies using non-B DB database reveal clustering of several non-B DNA forming motifs at the region spanning exon 4 of BCL11B gene. In order to biochemically evaluate the potential of non-B DNA structure formation, two different regions of exon 4 were PCR amplified and cloned. Using bisulfite modification assay we demonstrate that, single strandedness exists at both region I and II of BCL11B exon 4, when the region is present on a plasmid DNA. Bisulfite reactivity on chromosomal DNA confirmed existence of such altered DNA structures in the context of human genome. In vitro gel shift assays showed formation of both intra and intermolecular G-quadruplexes. Primer extension studies revealed that non-B DNA structures could block polymerization during replication on a plasmid, leading to DNA replication arrest. Extrachromosomal assays showed that non-B DNA structure motifs, in contrast to its mutants, blocked transcription leading to reduced expression of green fluorescent protein (GFP) within cells. Many non-B DNA-forming sequences have been mapped to regions of common chromosomal breakpoints in human tumors, known as “hotspots”, which are associated with leukemia, lymphomas and genomic disorders. Thus, alternative DNA conformations are believed to contribute to mutations, deletions and other genetic instability, leading to the deregulation of cancer-related genes in malignant diseases such as leukemia and lymphoma. Activation induced cytidine deaminase (AID), is an essential enzyme involved in antibody diversification of immunoglobulin genes. However, aberrant AID expression in B- cell and non-B cell background is reported in various cancers including leukemia and lymphoma. AID activity requires single stranded DNA (ssDNA) as a substrate. Since activation induced cytidine deaminase (AID) deaminates cytosines when present on a single stranded DNA and its expression is deregulated in many cancers, we investigated the role of AID in BCL11B gene mutagenesis. We observed substantial AID expression in many T-cell leukemic cell lines. Thus, we hypothesize that AID might be targeted to single stranded DNA present at BCL11B exon 4 due to formation of non-B DNA structures such as G-quadruplexes causing AID mediated deamination, further leading to nucleotide alterations and the mutational signature observed at BCL11B exon 4 resulting in T-ALL. Based on our findings, we propose that single strandedness resulted due to formation of non-B DNA structures such as G-quadruplex DNA, triplex DNA or cruciform DNA during physiological processes like DNA replication and transcription at exon 4 of BCL11B, can act as the target for AID. Thus, our findings uncover a new possible link between non-B DNA structure motifs and AID expression in causing mutations at BCL11B exon 4 which could lead to T cell leukemia genesis. BCL11B is a bifunctional transcriptional regulator that can act as a repressor and transactivator, and is known to differentially control the expression of specific genes in a context-dependent manner. In order to understand the transcriptional network involving BCL11B, it was cloned, overexpressed and purified from E. coli. To investigate the DNA binding properties of BCL11B protein, electrophoretic mobility shift assays were performed. Our results lead to identification of a specific sequence motif that is responsible for DNA binding. Competition experiments in presence of specific and nonspecific oligomers further confirmed the binding specificity. Thus, in the present study, we have characterized the binding properties of nonamer binding domain of RAG1, emphasizing its pathological relevance in causing genomic instability in lymphoid cells. The study may help in better understanding of RAG induced genomic instability in lymphoid tissues and role of aberrant AID expression in inducing mutations at BCL11B Zinc finger domain, leading to its deregulation and culminating into T-cell leukemia

Introduction: Testicular microlithiasis is an uncommon condition characterized by calcifications within the seminiferous tubules. The true prevalence in a normal population has not been defined. Methods: A review of the literature with emphasis on the connection between testicular microlithiasis and testicular malignancy was carried out. Results: Testicular microlithiasis is associated with different testicular pathologies, including testicular cancer. However, a direct causative connection between testicular microlithiasis and testicular pathologies is not supported by the literature. Conclusions: Patients with testicular microlithiasis should be followed up regularly. Further investigations concerning the etiology of testicular microlithiasis remain to be done. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Magister Chirurgiae Dentium (MChD) / Oral Squamous Cell Carcinoma (OSCC) patients suffer from the terrible consequences of the disease and its treatment modalities, and as a result, their Quality of Life (QoL) and Oral Health-related Quality of Life (OHRQoL) is badly affected, especially due to functional limitation, physical disability and psychological disability that they encounter before, during and after treatment. There is a need for more research on OHRQoL of OSCC patients at various treatment intervals. The present study focused on investigating OHRQoL of OSCC patients at the post-treatment phase.

Effective prevention, or treatment, of invasive fungal infection in the neutropenic patient has hitherto been unsatisfactory because of either an inadequate anti-fungal spectrum of the agent or important toxicity. Itraconazole is effective against a broad spectrum of the opportunistic pathogens seen in Europe and North America. Prior problems with absorption, e.g. in the marrow transplant recipient, have been overcome with the introduction of an oral solution and an i.v. preparation. The deliberations of an expert meeting held in June, 1998 include recommendations on which patient requires one of these new preparations based on clinical trials, the dose and route. Important drug interactions are also detailed. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Computed tomography urography (CTU) is today the imaging method used to investigate patients with suspected urinary tract malignancy, replacing the old imaging method intravenous pyelography (IVP) about a decade ago. The downside of this shift was that the effective radiation dose to the examined patient was eight times higher for CTU compared to IVP. Based on four different studies, the present thesis focused on efforts to reduce the CTU radiation dose.   In study I, the number of cysts and solid lesions in the separate scan phases was evaluated in 57 patients undergoing four-phase CTU 1997-98. The number of scans was reduced from four to three when the nephrographic scan was abolished following study I. Study II registered the diameter of renal cell carcinoma (RCC) and the presenting symptoms in the total number of patients (n=232) diagnosed with RCC between 1997 and 2003. The results from study II showed that the critical size for RCCs to cause macroscopic hematuria was ≥ 4 cm. Study III was a dose-escalation study aimed to decide the minimal possible tube load in the unenhanced and excretory phase scans if the low dose images are reviewed together with normal dose corticomedullary phase images. Study III showed that it is possible to reduce the mean effective dose in three phase CTU from 16.2 mSv to 9.4 mSv with a combined low and normal dose CTU protocol. Study IV investigated the changes in the CTU protocol between 1997 and 2008, and the development of the effective radiation dose. Study IV clarified how the CTU protocol has changed between 1997 and 2008 and as a result the mean effective radiation dose to patients undergoing CTU in 2008 is only 39% of the effective dose in 1997.   In conclusion, the findings from the studies included in this thesis have contributed to a reduced radiation dose to patients undergoing CTU. The mean effective dose from CTU is at present only three times higher compared to that from the IVP.

As Síndromes mielodisplásicas (SMD) são doenças clonais da célula progenitora hematopoética, cursando com citopenias, medula óssea displástica e tendência à evolução para leucemia. As SMD secundárias estão associadas a fatores de risco como doenças congênitas (Anemia de Fanconi), doenças hematológicas adquiridas (aplasia medular, HPN), exposição à quimioterápicos (alquilantes, inibidores de topoisomerase II) e radioterapia e substâncias químicas (benzeno, petróleo). Agentes imunossupressores associados ou não a fatores hemopoéticos particularmente utilizados para tratamento da Aplasia medular também se associam à SMD secundária. A OMS recentemente adotou o termo síndrome mielodisplásica/neoplasia mielóde (SMD/NM) relacionada à terapêutica para englobar casos de neoplasias mielóides que preencham critérios morfológicos não somente de SMD, mas também de leucemia mielóide aguda (LMA) ou neoplasias mieloproliferativas. O objetivo do trabalho foi analisar dados clínicos, morfológicos e citogenéticos de 42 portadores de SMD/NM secundária em uma coorte de pacientes diagnosticados no SH-HCFMUSP no período de 1987 a 2008. Vinte e três pacientes (54,8%) eram homens, com mediana de idade de 53,5 (4-88) anos. 45,2% eram portadores de doenças onco-hematológicas, 26,2% de anemia aplástica, 14,3% de tumores sólidos e 14,3% de outras doenças (auto-imunes e transplante de órgãos sólidos). 33% dos pacientes utilizaram exclusivamente QT, 26% combinação QT e RT, 2% RT isolada e 28% agentes imunossupressores. Cinco (11,9%) pacientes haviam sido submetidos a TCTH autólogo para tratamento de doença oncohematológica prévia. A mediana da latência entre a doença primária e a SMD secundária foi de 85 meses (23- 221 meses). Oito pacientes foram submetidos ao TCTH alogênico aparentado para tratamento da SMD secundária. Anemia, neutropenia, plaquetopenia e blastos circulantes foram observados em 64,3%, 54,8%, 78,6% e 26,2% dos casos respectivamente. Cerca de 1/3 dos aspirados medulares apresentavam hemodiluição, 29,7% apresentavam hipocelularidade global, 62,2% apresentavam contagem de blastos superior a 5% e 14,3% sideroblastos em anel acima de 15%. Displasia da série eritróide, granulocítica e megacariocítica foi observada em 79,4%, 77,1% e 68,2% dos casos respectivamente. A histologia medular realizada em 22 casos revelou hipocelularidade global, ALIPs e nódulos linfóides em 9,1%, 23,8% e 40,9% dos casos. A detecção por imunoistoquímica de células CD34>1%, CD117>1%, agrupamento de células CD34+ e de CD117+ e da proteína p53+ foi observada respectivamente em 77,2%, 82,3%, 59%, 29,4% e 33,3% dos casos. Anormalidades clonais foram observadas em 84,3% dos casos, com grande predomínio das não balanceadas (96%), sendo 37% com monossomia 7, 44,4% cariótipos complexos e 18% com outras anormalidades . A mediana de sobrevida de sobrevida global foi de 5,7 meses, pacientes submetidos ao TCTH alogênico para tratamento da SMD/NM secundária tiveram mediana de 40 meses (p=0,007). Fatores associados à pior sobrevida incluíram: doença oncohematológica prévia, baixa contagem plaquetária, elevação de DHL e ferritina, presença de células CD117+ agrupadas, imunoexpressão positiva da p53, citogenética anormal, IPSS intermediário II ou alto risco. Nenhum parâmetro estudado do aspirado medular se associou à sobrevida. Houve tendência à associação da imunoexpressão positiva de p53 a cariótipo anormal e IPSS de maior risco. Não se observou associação entre a presença de ALIP, porcentagem de blastos na morfologia medular e células CD34+ e CD117+. Estes dados reforçam a importância da análise citogenética e da imunoistoquímica da biópsia de medula óssea para diagnóstico e prognóstico das SMD secundárias e do TCTH alogênico no seu tratamento. Mais estudos com maior número de casos devem ser realizados para confirmar a importância do escore IPSS na SMD secundárias, provavelmente substituindo a porcentagem de blastos ao aspirado medular, pela presença de células precursoras detectadas por imunoistoquímica / Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders, characterized by cytopenias, dysplastic bone marrow (BM) and propensity to progress to acute myeloid leukemia. Secondary MDS are associated with risk factors such as congenital disorders (Fanconis anemia), acquired bone marrow failures, exposure to chemotherapy (alkylating agents, topoisomerase II inhibitors) agents and radiation and chemicals (benzene, petroleum). Immunosuppressive agents associated with hematopoietic growth factors are also associated with secondary MDS. The WHO classification has recently adopted the term therapy-related myeloid neoplasms for cases of myeloid malignancies that fulfill morphological criteria not only for MDS but also for AML or myeloproliferative neoplasms.The aim of the study was to analyze clinical, morphological and cytogenetic features of 42 patients with secondary MDS/MN in a cohort of patients diagnosed at our institution from 1987 to 2008. 23 patients (54.8%) were male, median age 53.5 (4-88) years. 45.2% had primary hematologic malignancies, 26.2% aplastic anemia, 14.3% solid tumors and 14.3% other diseases (autoimmune diseases and solid organ transplantation). 33% had undergone chemotherapy alone, 2% RT alone, 26% both modalities and 28% immunosuppressive agents. Five (11.9%) patients had undergone autologous HSCT for treatment of previous malignancies. The median latency between the primary disease and secondary MDS/MN was 85 (23-221) months. Eight patients underwent allogeneic HSCT (allo- HSCT) for treatment of related secondary MDS. Anemia, neutropenia, thrombocytopenia and peripheral blasts were observed in 64.3%, 54.8%, 78.6% and 26.2%, respectively. BM aspirates was poorly representative in 1/3 of cases, 29.7% global hypocellularity, 62.2% more than 5% of blast counts and 14.3% more than 15% of ring sideroblasts. Dysplasia in erythroid, granulocytic and megakaryocytic series was observed in 79.4%, 77.1% and 68.2%, respectively. Twenty two BM biopsies were performed. Global hypocellularity, ALIP and lymphoid nodules were shown in 9.1%, 23.8% and 40.9%. The immunohistochemistry showed more than 1% of CD34+ and CD117+ cells, clusters of CD34+ and CD117+ and immunoexpression of p53 protein in 77.2%, 82.3%, 59%, 29.4% and 33.3%, respectively. Clonal abnormalities were observed in 84.3% of cases with high prevalence of unbalanced (96%) rearrangements. 37% showed monosomy 7 and 44.4% complex karyotypes. The median overall survival was 5.7 for all patients and 40 months for patients treated with allo-HSCT (P=0.007). Hematologic malignancies, low platelet count, serum high LDH and ferritin, detection of CD117+ clusters, positive immunoexpression of p53, abnormal cytogenetics, intermediate-II or high-risk IPSS groups were associated with poor survival. No parameter studied from bone marrow aspirate had impact in survival. p53 expression was associated to abnormal karyotype (P=0.092) and IPSS risk (P=0.054). There was no association between the presence of ALIP, BM blast counts and immunoexpression of CD34+ and CD117+. Our study shows that cytogenetic analysis and BM immunohistochemistry are very important in diagnosis and prognosis, and that allo-HSCT could improve the survival of secondary MDS/MN. More studies with larger numbers of cases should be conducted to confirm the importance of the IPSS for secondary MDS, probably replacing the bone marrow aspirate blast counts by the immunohistochemistry detection of precursor cells