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Le illness in peripheral blood or bone marrow even when very sensitive immunophenotypic or molecular procedures are used to appear for residual illness. These individuals are thought of to have accomplished a minimal residual disease (MRD) unfavorable status.17-20 Various phase II trials have demonstrated that patients reaching MRD [http://about:blank Est and handle {the most|probably the most|essentially] negativity have a signif-icantly longer survival than those that stay MRD constructive, and this is accurate for individuals 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) not too long ago revealed that individuals acquiring MRD negativity had significantly longer progression-free and general survivals, irrespectively on the remedy received.18 Regrettably, nevertheless, some of these studies had been flawed by inappropriate statistical analysis, specifically the measurement of time-to-event outcomes from treatment initiation.27 Furthermore, there are lots of caveats to the use of MRD evaluation in patients with CLL.28 Initial, CLL remains incurable and at the very least 30  of patients who realize MRD negativity after front-line therapy with fludarabine-cyclophosphamide (FC) or rituximab-FC sooner or later expertise a disease relapse within five years.18 Secondly, unlike the scenario in acute promyelocytic leukemia or chronic myeloid leukemia,29,30 there's no formal proof of a therapeutic advantage of re-treatment upon documentation of MRD positivity following an initial MRD-negative response in comparison to remedy in the time of clinical relapse. In reality, quite handful of studies have demonstrated a clear advantage from MRD eradication or consolidation therapy in CLL,31,32 and some of your strategies tested, despite the fact that efficient, resulted in substantial toxicity.33-35 Thirdly, it might be argued that MRD assessment is just a surrogate for evalution of other adverse prognostic markers because, as an illustration, individuals having a 17p014 Ferrata Storti Foundation. That is an open-access paper. doi:ten.3324/haematol.2013.099796 The on line version of this [http://landscape4me.com/members/father9weeder/activity/3945971/ Nutrients inside a complicated of other myriad constituents {that] article features a Supplementary Appendix. Manuscript received on October 17, 2013. Manuscript accepted on December 31, 2013. Correspondence: jdelgado@clinic.ub.eshaematologica | 2014; 99(five)R. Santacruz et al.deletion possess a greater probability of remaining MRD-positive immediately after therapy compared to sufferers devoid of this chromosome abnormality.18 For all these factors, present recommendations for the management of individuals with CLL advocate MRD assessment only within clinical trials with "curative intention".36 With all this facts in mind, we retrospectively evaluated the effect of MRD on the outcome of patients with CLL receiving any front-line therapy within the context of an extremely detailed prognostic evaluation, such as not too long ago described recurrent gene mutations.survival and overall survival were calculated working with a landmark analysis. All calculations had been performed applying either SPSS, version 18.0, or R, version 3.0.1. Two-sided P values 0.05 had been viewed as statistically important. A detailed explanation in the statistical approaches is obtainable in the On the web Supplement.Results Baseline characteristicsThe median age of the whole cohort was 58 years (range, 27-93 years), as well as the percentage of patients older than 70 years was 22 . Based on D ner's hierarchical model, 17/221 (eight ) and 40/221 (18 ) individuals had 17p deletion and 11q deletion, respectively. TP53 mutations had been documented in 22/193 (11 ).
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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.