Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes
ABSTRACT The aims of this study were to identify the most significant prognostic factors in myelodysplastic syndromes (MDS) taking into account both their values at clinical onset and their changes in time and to develop a dynamic model for predicting survival and leukemic evolution that can be applied at any time during the course of the disease.
We studied a learning cohort of 426 MDS patients diagnosed at the Department of Hematology, San Matteo Hospital, Pavia, Italy, between 1992 and 2004, and a validation cohort of 739 patients diagnosed at the Heinrich-Heine-University Hospital, Düsseldorf, Germany, between 1982 and 2003. All patients were reclassified according to WHO criteria. Univariable and multivariable analyses were performed using Cox models with time-dependent covariates.
The most important variables for the prognostic model were WHO subgroups, karyotype, and transfusion requirement. We defined a WHO classification-based prognostic scoring system (WPSS) that was able to classify patients into five risk groups showing different survivals (median survival from 12 to 103 months) and probabilities of leukemic evolution (P < .001). WPSS was shown to predict survival and leukemia progression at any time during follow-up (P < .001), and its prognostic value was confirmed in the validation cohort.
WPSS is a dynamic prognostic scoring system that provides an accurate prediction of survival and risk of leukemic evolution in MDS patients at any time during the course of their disease. This time-dependent system seems particularly useful in lower risk patients and may be used for implementing risk-adapted treatment strategies.
SourceAvailable from: Parisa Farzam[Show abstract] [Hide abstract]
ABSTRACT: Noninvasive measurement of hemodynamics at the microvascular level may have a great impact on oncology in clinics for diagnosis, therapy planning and monitoring, and, in preclinical studies. To this end, diffuse optics is a strong candidate for noninvasive, repeated, deep tissue monitoring. In this multi-disciplinary, translational work, I have constructed and deployed hybrid devices which are the combination of two qualitatively different methods, near infrared diffuse optical spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS), for simultaneous measurement of microvascular total hemoglobin concentration, blood oxygen saturation and blood flow. In a preclinical study, I applied the hybrid device to monitor the response of renal cell carcinoma in mice to antiangiogenic therapy. The results suggest that we can predict the output of therapy from early hemodynamic changes, which provide us with valuable information for better understanding of the tumor resistance mechanism to antiangiogenic therapies. In two in vivo studies in human volunteers, I have developed protocols and probes to demonstrate the feasibility of noninvasive diffuse optical spectroscopy to investigate the pathophysiology of bone. First study was study on the physiology of the patella microvasculature, the other introduced the manubrium as a site that is rich in red bone mar- row and accessible to diffuse optics as a potential window to monitor the progression of hematological malignancies. Overall, during my Ph.D., I have developed instrumentation, algorithms and protocols and, then, applied this technique for preclinical and clinical investigations. My research is a link between preclinical and clinical studies and it opens new areas of applications in oncology.01/2014, Degree: PhD, Supervisor: Turgut Durduran
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ABSTRACT: Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis. MDS represent a complex hematological problem: differences in disease presentation, progression and outcome have necessitated the use of classification systems to improve diagnosis, prognostication, and treatment selection. However, since a single biological or genetic reliable diagnostic marker has not yet been discovered for MDS, quantitative and qualitative dysplastic morphological alterations of bone marrow precursors and peripheral blood cells are still fundamental for diagnostic classification. In this paper, World Health Organization (WHO) classification refinements and current minimal diagnostic criteria proposed by expert panels are highlighted, and related problematic issues are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies. Although, in the future, morphology should be supplemented with new molecular techniques, the morphological approach, at least for the moment, is still the cornerstone for the diagnosis and classification of these disorders.Mediterranean Journal of Hematology and Infectious Diseases 04/2015; 7(1):e2015035. DOI:10.4084/MJHID.2015.035
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ABSTRACT: Background. Hematologic improvement (HI) occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT) but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC) transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient's course in detail and review the literature on HI with chelation. Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.01/2015; 2015:253294. DOI:10.1155/2015/253294