Myelodysplastic syndromes in South America: a multinational study of 1080 patients.

There are previously reported data describing differences between Asian and European patients with Myelodysplastic Syndromes (MDS), few direct comparisons based on cancer registration characteristics or using cohorts to validate scoring systems. This is the first study from South-America, which attempts to describe demographic, clinical features, and outcome of MDS patients. We retrospectively analyzed 1,080 patients with de novo MDS from Argentina (635), Brazil (345), and Chile (100). Chilean patients were younger (P = 0.001) with female preponderance (P = 0.071). Brazilian series showed a higher predominance of RARS subtype regarding FAB and WHO classifications (P < 0.001). Hemoglobin levels were significantly lower in Brazilian and Chilean series (P < 0.001), and Chilean series also showed a lower platelet count (P = 0.028), with no differences concerning the neutrophil count, % BM blast, and the distribution of cytogenetic risk groups (P > 0.05). Chilean series depicted a lower overall survival (OS; 35 months vs. 56 months-Argentine; 55 months-Brazil, P = 0.030), which was consistent with a higher predominance of the high-risk group according both to the IPSS and IPSS-R (P = 0.046 and P < 0.001). The IPSS-R system and its variables showed a good reproducibility to predict clinical outcome for the whole South-American population. Epidemiological and clinical characteristics, distribution among prognostic subgroups, the OS, and the access to disease modifying therapies were more similar between Argentinean and Brazilian compared with Chilean MDS series. This will need further analysis in a larger group of patients. Descriptive and comparative studies are necessary to establish epidemiological features useful for public health attitudes to generate suitable therapeutic schemes.

Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib.

Eosinophilia is common in myeloproliferative disorders (MPDs) with abnormalities of chromosome band 5q31-33, including those that present with t(1;5)(q23;q33). With the development of rational drug therapy, characterization of the molecular targets for these translocations could guide treatment and affect patient survival. We cloned the t(1;5)(q23;q33) and showed that it fuses platelet-derived growth factor receptor beta (PDGFRB) to the coiled-coil domains of a novel partner protein, myomegalin. Using two-color interphase fluorescence in situ hybridization (FISH), we also demonstrated that the eosinophils are clonal in these disorders. Imatinib mesylate has recently been shown to be efficacious in MPDs with PDGFR activation. Therefore, following our molecular studies, we were able to redirect this patient's treatment. Although she had refractory and progressive disease, once imatinib was started, complete clinical and hematologic remission, as well as major cytogenetic response, was achieved. Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family.

Fatores de crescimento hemopoéticos nas síndromes mielodisplásicas / Hematopoietic growth factors in myelodysplastic syndromes

Fatores de crescimento hemopoéticos, como a eritropoetina e a associação da eritropoetina com o fator estimulante de colônias de granulócitos (G-CSF) são utilizados para manejo da anemia, particularmente nas síndromes mielodisplásicas de baixo risco (Anemia refratária e Anemia refratária com sideroblastos em anel e mielodisplasias com sistema de escore de prognóstico internacional de risco baixo ou intermediário I). O nível sérico de eritropoetina e a necessidade transfusional pré-tratamento podem identificar pacientes com melhor chance de resposta a essas terapêuticas de alto custo. O uso indiscriminado de G-CSF em portadores de neutropenia crônica não está indicado, devendo ser individualizado.

Treatment with growth factors, particularly erythropoietin (EPO) alone or in association with granulocyte colony-stimulating factor (G-CSF), has been useful in the management of anemia in low-risk patients with myelodysplastic syndromes (refractory anemia, refractory anemia with ringed sideroblasts, low or intermediate-1 IPSS groups). Two pre-treatment variables (serum EPO levels and red blood cell-transfusion needs) can predict erythroid responses to these high cost treatments. The indiscriminate use of G-CSF in neutropenic patients is not recommended although it can be useful in specific situations.

Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas / Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

Agentes imunossupressores, como a globulina antitimocítica (GAL) ou antilinfocítica (GAL) e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR) e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG). É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO).

Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.