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These sufferers are considered to have accomplished a minimal residual illness (MRD) adverse status.17-20 Several phase II trials have demonstrated that individuals reaching MRD negativity possess a signif-icantly longer survival than people that stay MRD optimistic, and this is true for patients treated with standard chemotherapy,21,22 monoclonal antibodies,23 chemoimmunotherapy,24 or stem cell transplantation.25,26 In addition, a phase III trial performed by the German CLL Study Group (GCLLSG) lately revealed that individuals acquiring MRD negativity had considerably longer progression-free and general survivals, irrespectively on the remedy received.18 Sadly, nonetheless, a few of these research had been flawed by inappropriate statistical analysis, specifically the measurement of time-to-event outcomes from therapy initiation.27 Furthermore, there are several caveats for the use of MRD analysis in sufferers with CLL.28 1st, CLL remains incurable and at the very least 30  of sufferers who reach MRD negativity soon after front-line therapy with fludarabine-cyclophosphamide (FC) or rituximab-FC at some point encounter a disease relapse inside 5 years.18 Secondly, unlike the predicament 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 with remedy in the time of clinical relapse. The truth is, really handful of research have demonstrated a clear benefit from MRD eradication or consolidation therapy in CLL,31,32 and a few of the methods tested, although successful, resulted in considerable toxicity.33-35 Thirdly, it may be argued that MRD assessment is simply a surrogate for evalution of other adverse prognostic markers since, for example, sufferers having a 17p014 Ferrata Storti Foundation. That is an open-access paper. doi:10.3324/haematol.2013.099796 The on line version of this 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 have a larger probability of remaining MRD-positive just after therapy when compared with sufferers without the need of this chromosome abnormality.18 For all these causes, present suggestions for the management of patients with CLL advocate MRD assessment only within clinical trials with "curative intention".36 With all this information in thoughts, we retrospectively evaluated the effect of MRD around the outcome of patients with CLL getting any front-line therapy within the context of a very detailed prognostic evaluation, including not too long ago described recurrent gene mutations.survival and overall survival have been calculated working with a landmark analysis. All calculations were performed applying [https://www.medchemexpress.com/RR6.html MedChemExpress RR6] either SPSS, version 18.0, or R, version three.0.1. Two-sided P values 0.05 have been deemed statistically important. A detailed explanation in the statistical approaches is out there within the On line Supplement.Final results Baseline characteristicsThe median age with the entire cohort was 58 years (variety, 27-93 years), plus the percentage of sufferers older than 70 years was 22 . According to D ner's hierarchical model, 17/221 (8 ) and 40/221 (18 ) individuals had 17p deletion and 11q deletion, respectively.Le disease in peripheral blood or bone marrow even when extremely sensitive immunophenotypic or molecular procedures are made use of to appear for residual illness.
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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.