Onze doentes evoluíram para leucemia aguda; estes têm, em média, eritropoietina sérica superior (p < 0,05). Adicionalmente, a eritropoietina sérica acima do limite superior da normalidade associa-se a menor sobrevivência (p = 0,0336). Após ajuste do modelo de regressão de Cox, o valor preditivo da eritropoietina para a sobrevivência global manteve-se (p < 0,001). Em análise multivariada, a eritropoietina sérica demonstrou ser um factor de prognóstico independente (p < 0,001). Discussão: A eritropoietina sérica é um factor preditivo de resposta à terapêutica com eritropoietina subcutânea, sendo que os doentes com síndrome mielodisplásica com valores mais elevados de eritropoietina apresentam uma pior resposta à administração de eritropoietina, mesmo com doses mais elevadas. A nossa amostra demonstra que a eritropoietina sérica apresenta também valor prognóstico, e em todos os subtipos de síndrome mielodisplásica. Além disso, isoladamente ou em associação com outros factores ou índices de prognóstico, poderá melhorar o valor prognóstico de índices como o International Prognostic Scoring System, uma vez que valores elevados de eritropoietina estão associados a progressão para leucemia aguda e, consequentemente, a menor sobrevivência. Conclusão: Os resultados sugerem que o aumento dos níveis séricos de eritropoietina ao diagnóstico pode constituir um factor de mau prognóstico em doentes com síndrome mielodisplásica, associando-se a maior risco de evolução para leucemia aguda e menor sobrevivência global. Palavras-chave: Eritropoietina; Prognóstico; Síndrome Mielodisplásica. ABSTRACT Introduction:This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and β2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System. Material and Methods:Our aim was to analyze serum´s erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology. Results: Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q-syndrome (p < 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p < 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum ery...

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants—SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters’ SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

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Background: Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder associated with a significative risk of evolution to acute leukemia. It can either present as primary disease or secondary to other myeloproliferative neoplasms. It's predominantly a disease of the elderly, with a median age at diagnosis of 65 years. Pharmacological therapy directed at symptom control has not shown to improve survival and, despite therapeutic advances with the Janus-Kinase (JAK) inhibitors, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment. Due to most patients advanced age and comorbidities, increased risk of graft failure, HSCT is challenging and requires specialized teams. Aim: To assess the results of allo-HSCT in myelofibrosis patients in our center and identify prognostic factors. Methods: Observational retrospective study including patients with previous diagnosis of MF (primary or secondary), referred to our center who underwent allo-HSCT between May 2001 and May 2016. Pre-transplant DIPSS, HCT-CI and Lille scores were applied. Neutrophil and platelet engraftment were defined as the first of three and seven consecutive days above 500/μL and 20,000/μL respectively. Correlations between factors were calculated using Spearman's rho (ρ). Survival was estimated using Kaplan-Meyer method. Statistical significance was defined as p<0.05. Results: In time period, 21 patients were transplanted in our center, with a median age of 51 years (21-67y); male:female ratio 1:1.1. Six patients had a previous story of Essential Thrombocytemia (ET). At diagnosis splenomegaly was present in 18 patients, 6 of them having been submitted to splenectomy and 5 of them having achieved spleen reduction with pharmacological therapy (hydroxicarbamide or ruxolitinib). Previous lines of treatment also included best supportive care, erythropoietin, danazol, interferon, and anagrelide. Prognostic score DIPSS was Intermediate-1 in 10 patients and intermediate-2 in the remaining 11. Thirteen had HCT-CI score of zero, 4 of 1 and 3 of 2. Eight patients had a Lille score of zero, 8 of 1, and 3 scored 2 points. Conditioning regimen was applied as follows: 11 patients had fludarabin-busulphan based reduced intensity (RIC) regimen, and the remainder had busulfan-cyclophosphamide based myeloablative (MAC) regimen. All patients underwent allo-HSCT, 18 from matched related donor and 3 from matched unrelated donor. Median time to neutrophil and platelet engraftment was 14.0 days (8;28) and 14.0 days (5;41) respectively. A significant correlation between time to neutrophil engraftment and overall survival (OS) (ρ=-0.589; p=0.006). Ten patients developed chronic GVHD. At present time 12 patients are alive, 11 in hematological remission. Median Karnofsky score is 90% (60-90). Median overall survival is 50 months; survival at 5 year is 90%. Nine patients died (8 due to transplant related complications). No statistical significant difference for OS was found comparing primary vs secondary MF, splenomegaly, JAK2 status, MAC or RIC and DIPSS risk categories. No graft failure occurred. Neither donor lymphocyte infusions nor second transplants were performed. Conclusion: MF remains a very challenging condition to treat with a very poor prognosis. Shorter neutrophil engraftment was correlated with better OS. Often, older patients are not eligible for more aggressive therapies. In our group of patients there were no significant statistical differences in OS between the use of MAC or RIC. No other prognostic factors were found in this analysis, having to be taken into account its small size. Disclosures No relevant conflicts of interest to declare.