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    ABSTRACT: Abstract The PRAME and WT1 transcript levels were simultaneously measured in 312 bone marrow samples collected from newly diagnosed myelodysplastic syndromes (MDS) patients and 111 samples collected during the treatment of 17 patients. Both the positive rate and the >1-log increase expression frequency of PRAME were similar to those of WT1 (74.4 % vs 77.6%; 51.6% vs 49.0%), and 88.1% of the patients overexpressed at least one marker. Moreover, the frequencies of PRAME expression with higher degrees of increase were significantly higher compared with those of WT1 expression (>2-log increase: 30.8% vs 3.8%; >3-log increase: 9.0% vs 0%; all p<0.001). PRAME had a higher log increase than WT1 in 53.3% of the patients with overexpressed WT1. Both PRAME and WT1 transcript levels generally fluctuated within the normal range after hematopoietic stem cell transplantation in all 10 patients in continuous complete remission. Six out of seven patients were predicted relapse by the combined detection: sustained positivity or significant increase to be positive of both WT1 and PRAME in three patients, earlier by PRAME than WT1 or by PRAME alone in three patients. Thus, the PRAME and WT1 transcripts constitute a good molecular marker combination for monitoring minimal residual disease in MDS.
    Leukemia & lymphoma 10/2012; · 2.61 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic stem cell transplantation is still the only potentially curative treatment for patients with myelodysplastic syndromes. Improvements in donor selection, supportive care and the introduction of reduced-intensity conditioning have led to a decrease in early transplant mortality. However, relapse rates have not changed significantly in recent years. Furthermore, treatment options for patients relapsing after hematopoietic stem cell transplantation are limited and often short-lived. Thus, optimizing the post-transplant outcome by maintenance approaches or minimal residual disease-directed preemptive therapy is an important goal of current clinical research. Further strategies aiming at an improved prevention of graft-versus-host disease are currently under investigation.
    Expert Review of Hematology 12/2011; 4(6):669-80. · 2.38 Impact Factor
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    ABSTRACT: Relapse has become the leading cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Despite improved understanding of the biology that underlies the graft-versus-leukemia/tumor effect the relapse rate did not decrease over the past 20 years. In general, prognosis is poor for patients who relapsed to an allograft since effective treatment options are limited. Here, we review the available and upcoming treatment approaches for relapse. Treatment of relapse after allogeneic HSCT has been rarely investigated systematically and results differ substantially from diseases. Withdrawal of immunosuppressive medication, donor lymphocyte infusions with or without chemotherapy and/or second allogeneic HSCT are the most used options. New specific cellular approaches such as disease-specific T-cells, alloreactive natural killer cells or vaccination strategies are under investigation. Novel agents such as tyrosine-kinase inhibitors, hypomethylating agents, monoclonal antibodies, immunomodulating drugs, or proteasome-inhibitors either alone or in combination with adoptive immunotherapy are upcoming promising options, but valid data are lacking so far. With some exceptions (chronic myeloid leukemia), treatment options for patients who relapse are limited. The results are poor and the majority of patients ultimately die of their disease. More effort and research is needed to prevent and treat relapse after allogeneic HSCT.
    Current opinion in oncology 03/2011; 23(2):203-8. · 4.09 Impact Factor

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May 20, 2014