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.
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ABSTRACT: Azacitidine (AZA) is standard care for patients with myelodysplastic syndrome (MDS) who have not had allogeneic stem cell transplantation. Chromosomal abnormalities (CA) including complex karyotype (CK) or monosomal karyotype (MK) are associated with clinical outcome in patients with MDS. We investigated which prognostic factors including CAs would predict clinical outcomes in patients with International Prognostic Scoring System (IPSS) higher risk MDS treated with AZA, retrospectively. CK was defined as the presence of three or more numerical or structural CAs. MK was defined as the presence of two or more distinct autosomal monosomies or single autosomal monosomy with at least one additional structural CA. A total of 243 patients who treated with AZA, were enrolled. CK was present in 124 patients and MK was present in 90 patients. Bone marrow blasts ≥15% and CK were associated with poorer response (P=0.038, P=0.007) and overall survival (OS) (P<0.001, P<0.001) independently. Although MK in CK group was not associated with prognosis, non-MK status in non-CK group reflected favorable OS (P=0.005). The group including >3 CAs was associated with poorer OS (group including <3 CAs vs. only three CAs, P=0.001; group with >3 CAs vs. only three CAs, P=0.001). CK was an important prognostic parameter associated with worse outcome. MK may predict poor survival in only non-CK status. The higher number of CAs was associated with poorer survival.12/2014; 49(4):234-40. DOI:10.5045/br.2014.49.4.234
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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) represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q)] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q) MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q) lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q) MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS.Hematology Research and Reviews 01/2015; 6:1-16. DOI:10.2147/JBM.S50482