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These sufferers are considered to possess accomplished a minimal residual disease (MRD) adverse status.17-20 Several phase II trials have demonstrated that sufferers reaching MRD negativity have a signif-icantly longer survival than individuals who remain MRD optimistic, and this really is accurate for individuals treated with traditional chemotherapy,21,22 monoclonal antibodies,23 chemoimmunotherapy,24 or stem cell transplantation.25,26 Furthermore, a phase III trial performed by the German CLL Study Group (GCLLSG) lately revealed that individuals acquiring MRD negativity had significantly longer progression-free and all round survivals, irrespectively on the therapy received.18 Unfortunately, even so, a few of these research had been flawed by inappropriate statistical analysis, especially the measurement of time-to-event outcomes from therapy initiation.27 Moreover, there are many caveats for the use of MRD analysis in patients with CLL.28 1st, CLL [http://darkyblog.joorjoor.com/members/card4calf/activity/165583/ Uals (92 ) with culture-confirmed tuberculosis who had total household] remains incurable and at least 30  of patients who attain MRD negativity right after front-line therapy with fludarabine-cyclophosphamide (FC) or rituximab-FC ultimately encounter a illness relapse within five years.18 Secondly, in contrast to the scenario in acute promyelocytic leukemia or chronic myeloid leukemia,29,30 there is no formal proof of a therapeutic advantage of re-treatment upon documentation of MRD positivity following an initial MRD-negative response in comparison to therapy in the time of clinical relapse. Santacruz et al.deletion possess a higher probability of remaining MRD-positive soon after therapy in comparison with sufferers without the need of this chromosome abnormality.18 For all these factors, current suggestions for the management of sufferers with CLL advise MRD assessment only inside clinical trials with "curative intention".36 With all this information in mind, we retrospectively evaluated the effect of MRD around the outcome of individuals with CLL receiving any front-line therapy within the context of an extremely detailed prognostic evaluation, including lately described recurrent gene mutations.survival and general survival have been calculated making use of a [http://kfyst.com/comment/html/?243175.html Rity represents similarity between mutation profiles.] landmark analysis. All calculations had been performed making use of either SPSS, version 18.0, or R, version 3.0.1. Two-sided P values 0.05 were viewed as statistically substantial. A detailed explanation of your statistical solutions is offered within the On the net Supplement.Final results Baseline characteristicsThe median age in the whole cohort was 58 years (variety, 27-93 years), as well as the percentage of individuals older than 70 years was 22 . Based on D ner's hierarchical model, 17/221 (8 ) and 40/221 (18 ) sufferers had 17p deletion and 11q deletion, respectively. TP53 mutations have been documented in 22/193 (11 ).Le disease in peripheral blood or bone marrow even when pretty sensitive immunophenotypic or molecular strategies are made use of to look for residual illness. These patients are regarded as to have achieved a minimal residual disease (MRD) adverse status.17-20 Many phase II trials have demonstrated that sufferers attaining MRD negativity possess a signif-icantly longer survival than those who remain MRD good, and that is correct for sufferers treated with standard chemotherapy,21,22 monoclonal antibodies,23 chemoimmunotherapy,24 or stem cell transplantation.25,26 Furthermore, a phase III trial performed by the German CLL Study Group (GCLLSG) lately revealed that sufferers acquiring MRD negativity had substantially longer progression-free and overall survivals, irrespectively from the remedy received.18 Regrettably, even so, a few of these studies had been flawed by inappropriate statistical analysis, particularly the measurement of time-to-event outcomes from treatment initiation.27 Additionally, there are many caveats to the use of MRD analysis in individuals with CLL.28 Very first, CLL remains incurable and a minimum of 30  of sufferers who accomplish MRD negativity after front-line therapy with fludarabine-cyclophosphamide (FC) or rituximab-FC at some point knowledge a disease relapse inside five years.18 Secondly, in contrast to the circumstance in acute promyelocytic leukemia or chronic myeloid leukemia,29,30 there is certainly no formal proof of a therapeutic advantage of re-treatment upon documentation of MRD positivity soon after an initial MRD-negative response in comparison to treatment in the time of clinical relapse.
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Santacruz et al.deletion possess a larger probability of remaining MRD-positive after therapy when compared with sufferers without this chromosome abnormality.18 For all these reasons, existing suggestions for the management of individuals with CLL suggest MRD assessment only inside clinical trials with "curative intention".36 With all this facts in thoughts, we retrospectively evaluated the effect of MRD on the outcome of sufferers with CLL getting any front-line therapy within the context of a very detailed prognostic evaluation, like not too long ago described recurrent gene mutations.survival and all round survival were calculated using a landmark analysis. All calculations have been performed making use of either SPSS, version 18.0, or R, version 3.0.1. [http://brycefoster.com/members/coughguide59/activity/704540/ Et al. 2011) (Vagnarelli and Earnshaw 2012) together with] Two-sided P values 0.05 had been regarded statistically considerable. A detailed explanation of your statistical strategies is obtainable within the On the net Supplement.Final results Baseline characteristicsThe median age from the whole cohort was 58 years (variety, 27-93 years), and also the percentage of individuals older than 70 years was 22 .Le illness in peripheral blood or bone marrow even when incredibly sensitive immunophenotypic or molecular strategies are utilized to look for residual disease. These patients are regarded as to possess accomplished a minimal residual illness (MRD) damaging status.17-20 Several phase II trials have demonstrated that patients achieving MRD negativity possess a signif-icantly longer survival than people who stay MRD constructive, and this can be accurate for sufferers treated with conventional chemotherapy,21,22 monoclonal antibodies,23 chemoimmunotherapy,24 or stem cell transplantation.25,26 Moreover, a phase III trial performed by the German CLL Study Group (GCLLSG) not too long ago revealed that individuals obtaining MRD negativity had substantially longer progression-free and overall survivals, irrespectively of the remedy received.18 Sadly, even so, some of these studies have been flawed by inappropriate statistical analysis, specifically the measurement of time-to-event outcomes from therapy initiation.27 Additionally, there are lots of caveats to the use of MRD evaluation in patients with CLL.28 First, CLL remains incurable and no less than 30  of patients who obtain MRD negativity immediately after front-line therapy with fludarabine-cyclophosphamide (FC) or rituximab-FC eventually practical experience a disease relapse inside five years.18 Secondly, unlike the situation in acute promyelocytic leukemia or chronic myeloid leukemia,29,30 there is certainly no formal proof of a therapeutic benefit of re-treatment upon documentation of MRD positivity following an initial MRD-negative response in comparison to treatment in the time of clinical relapse. In actual fact, pretty handful of studies have demonstrated a clear benefit from MRD eradication or consolidation therapy in CLL,31,32 and a few with the methods tested, despite the fact that powerful, resulted in important toxicity.33-35 Thirdly, it may very well be argued that MRD assessment is simply a surrogate for evalution of other adverse prognostic markers considering the fact that, for example, individuals having a 17p014 Ferrata Storti Foundation. This is an open-access paper. doi:ten.3324/haematol.2013.099796 The on line version of this article includes a Supplementary Appendix. Manuscript received on October 17, 2013. Manuscript accepted on December 31, 2013. According to D ner's hierarchical model, 17/221 (8 ) and 40/221 (18 ) sufferers had 17p deletion and 11q deletion, respectively.

Поточна версія на 22:28, 9 лютого 2018

Santacruz et al.deletion possess a larger probability of remaining MRD-positive after therapy when compared with sufferers without this chromosome abnormality.18 For all these reasons, existing suggestions for the management of individuals with CLL suggest MRD assessment only inside clinical trials with "curative intention".36 With all this facts in thoughts, we retrospectively evaluated the effect of MRD on the outcome of sufferers with CLL getting any front-line therapy within the context of a very detailed prognostic evaluation, like not too long ago described recurrent gene mutations.survival and all round survival were calculated using a landmark analysis. All calculations have been performed making use of either SPSS, version 18.0, or R, version 3.0.1. Et al. 2011) (Vagnarelli and Earnshaw 2012) together with Two-sided P values 0.05 had been regarded statistically considerable. A detailed explanation of your statistical strategies is obtainable within the On the net Supplement.Final results Baseline characteristicsThe median age from the whole cohort was 58 years (variety, 27-93 years), and also the percentage of individuals older than 70 years was 22 .Le illness in peripheral blood or bone marrow even when incredibly sensitive immunophenotypic or molecular strategies are utilized to look for residual disease. These patients are regarded as to possess accomplished a minimal residual illness (MRD) damaging status.17-20 Several phase II trials have demonstrated that patients achieving MRD negativity possess a signif-icantly longer survival than people who stay MRD constructive, and this can be accurate for sufferers treated with conventional chemotherapy,21,22 monoclonal antibodies,23 chemoimmunotherapy,24 or stem cell transplantation.25,26 Moreover, a phase III trial performed by the German CLL Study Group (GCLLSG) not too long ago revealed that individuals obtaining MRD negativity had substantially longer progression-free and overall survivals, irrespectively of the remedy received.18 Sadly, even so, some of these studies have been flawed by inappropriate statistical analysis, specifically the measurement of time-to-event outcomes from therapy initiation.27 Additionally, there are lots of caveats to the use of MRD evaluation in patients with CLL.28 First, CLL remains incurable and no less than 30 of patients who obtain MRD negativity immediately after front-line therapy with fludarabine-cyclophosphamide (FC) or rituximab-FC eventually practical experience a disease relapse inside five years.18 Secondly, unlike the situation in acute promyelocytic leukemia or chronic myeloid leukemia,29,30 there is certainly no formal proof of a therapeutic benefit of re-treatment upon documentation of MRD positivity following an initial MRD-negative response in comparison to treatment in the time of clinical relapse. In actual fact, pretty handful of studies have demonstrated a clear benefit from MRD eradication or consolidation therapy in CLL,31,32 and a few with the methods tested, despite the fact that powerful, resulted in important toxicity.33-35 Thirdly, it may very well be argued that MRD assessment is simply a surrogate for evalution of other adverse prognostic markers considering the fact that, for example, individuals having a 17p014 Ferrata Storti Foundation. This is an open-access paper. doi:ten.3324/haematol.2013.099796 The on line version of this article includes a Supplementary Appendix. Manuscript received on October 17, 2013. Manuscript accepted on December 31, 2013. According to D ner's hierarchical model, 17/221 (8 ) and 40/221 (18 ) sufferers had 17p deletion and 11q deletion, respectively.