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Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.

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Zeitschriftentitel: Blood
Personen und Körperschaften: Arpinati, Mario, Amabile, Marilina, Bochicchio, maria Teresa, Poerio, Angela, Bandini, Giuseppe, Bonifazi, Francesca, Stanzani, Marta, Castagnetti, Fausto, Rosti, Gianantonio, Martinelli, Giovanni, Baccarani, Michele
In: Blood, 116, 2010, 21, S. 1287-1287
Format: E-Article
Sprache: Englisch
veröffentlicht:
American Society of Hematology
Schlagwörter:
Cell Biology
Hematology
Immunology
Biochemistry
author_facet Arpinati, Mario
Amabile, Marilina
Bochicchio, maria Teresa
Poerio, Angela
Bandini, Giuseppe
Bonifazi, Francesca
Stanzani, Marta
Castagnetti, Fausto
Rosti, Gianantonio
Martinelli, Giovanni
Baccarani, Michele
Arpinati, Mario
Amabile, Marilina
Bochicchio, maria Teresa
Poerio, Angela
Bandini, Giuseppe
Bonifazi, Francesca
Stanzani, Marta
Castagnetti, Fausto
Rosti, Gianantonio
Martinelli, Giovanni
Baccarani, Michele
author Arpinati, Mario
Amabile, Marilina
Bochicchio, maria Teresa
Poerio, Angela
Bandini, Giuseppe
Bonifazi, Francesca
Stanzani, Marta
Castagnetti, Fausto
Rosti, Gianantonio
Martinelli, Giovanni
Baccarani, Michele
spellingShingle Arpinati, Mario
Amabile, Marilina
Bochicchio, maria Teresa
Poerio, Angela
Bandini, Giuseppe
Bonifazi, Francesca
Stanzani, Marta
Castagnetti, Fausto
Rosti, Gianantonio
Martinelli, Giovanni
Baccarani, Michele
Blood
Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
Cell Biology
Hematology
Immunology
Biochemistry
author_sort arpinati, mario
spelling Arpinati, Mario Amabile, Marilina Bochicchio, maria Teresa Poerio, Angela Bandini, Giuseppe Bonifazi, Francesca Stanzani, Marta Castagnetti, Fausto Rosti, Gianantonio Martinelli, Giovanni Baccarani, Michele 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v116.21.1287.1287 <jats:title>Abstract</jats:title> <jats:p>Abstract 1287</jats:p> <jats:sec> <jats:title>Background:</jats:title> <jats:p>Monitoring of minimal residual disease through RT-PCR analysis of bcr-abl transcripts allows early detection of CML relapse after allogeneic HSCT. However, the introduction of more sensitive techniques, such as quantitative PCR, may result in decreased specificity, leading to false positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods:</jats:title> <jats:p>In this study we reviewed the results of molecular analysis of bcr-abl transcripts in all patients with p210+ CML who underwent allogeneic HSCT from 1983 through 2007. Q-PCR analysis was started in 2002. Out of 189 patients, 87 patients had available Q-PCR data; of these, 63 patients with at least three separate Q-PCR data were included in the study. Median time to the 1st Q-PCR analysis was 2196 days (35-7823). Median age was 36 years (13-56), 62%/38% received transplant from a related/unrelated donor, 62% with BM. 32% were in accelerated phase (AP). Patients with at least one positive Q-PCR value (measured as a ratio of bcr-abl to abl of &gt; 0.001) were classified as Major Molecular Remission (MMR) patients. Each event was defined as one or more consecutive positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>60/63 patients are alive after a median follow up of 3693 days (898-9405). 6 have relapsed 2142 (1419-3746) days after transplant. 52 (83%) patients had at least one positive result (28 with a value of &gt;0.01, 24 with a value of &lt;0.01), whereas 11 (17%) had persistent undetectable transcripts. In MMR patients, 94 events occurred. 29 patients had only one event, while 6 had &gt;3 events. In 10 patients, the event occurred within 1 year after transplant, whereas in 28 it occurred after &gt;5 years. 6/52 MMR patients relapsed, as compared to 0/11 with persistent undetectable transcripts (p=0.19). Relapse did not correlate with the Q-PCR value, the number of events or the time to the event. Finally, of 46 MMR patients who did not relapse, 35 had undetectable transcripts at last follow up. Positive Q-PCR had low specificity (19%) and positive predictive value (12%) in predicting relapse after allogeneic HSC transplantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Our data confirm that the detection of low levels of bcr-abl transcripts (as based on Q-PCR) has a poor accuracy in predicting relapse, and it should not be considered as the sole indication to start treatment. It appears that fluctuation of bcr-abl transcript levels is common as late as &gt; 10 yrs after transplant, possibly suggesting the long term persistence of CML stem cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Rosti: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy.</jats:p> </jats:sec> Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT. Blood
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title Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_unstemmed Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_full Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_fullStr Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_full_unstemmed Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_short Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_sort long term study of the impact of quantitative molecular monitoring of bcr-abl transcripts on the risk of relapse of cml after allogeneic hsct.
topic Cell Biology
Hematology
Immunology
Biochemistry
url http://dx.doi.org/10.1182/blood.v116.21.1287.1287
publishDate 2010
physical 1287-1287
description <jats:title>Abstract</jats:title> <jats:p>Abstract 1287</jats:p> <jats:sec> <jats:title>Background:</jats:title> <jats:p>Monitoring of minimal residual disease through RT-PCR analysis of bcr-abl transcripts allows early detection of CML relapse after allogeneic HSCT. However, the introduction of more sensitive techniques, such as quantitative PCR, may result in decreased specificity, leading to false positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods:</jats:title> <jats:p>In this study we reviewed the results of molecular analysis of bcr-abl transcripts in all patients with p210+ CML who underwent allogeneic HSCT from 1983 through 2007. Q-PCR analysis was started in 2002. Out of 189 patients, 87 patients had available Q-PCR data; of these, 63 patients with at least three separate Q-PCR data were included in the study. Median time to the 1st Q-PCR analysis was 2196 days (35-7823). Median age was 36 years (13-56), 62%/38% received transplant from a related/unrelated donor, 62% with BM. 32% were in accelerated phase (AP). Patients with at least one positive Q-PCR value (measured as a ratio of bcr-abl to abl of &gt; 0.001) were classified as Major Molecular Remission (MMR) patients. Each event was defined as one or more consecutive positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>60/63 patients are alive after a median follow up of 3693 days (898-9405). 6 have relapsed 2142 (1419-3746) days after transplant. 52 (83%) patients had at least one positive result (28 with a value of &gt;0.01, 24 with a value of &lt;0.01), whereas 11 (17%) had persistent undetectable transcripts. In MMR patients, 94 events occurred. 29 patients had only one event, while 6 had &gt;3 events. In 10 patients, the event occurred within 1 year after transplant, whereas in 28 it occurred after &gt;5 years. 6/52 MMR patients relapsed, as compared to 0/11 with persistent undetectable transcripts (p=0.19). Relapse did not correlate with the Q-PCR value, the number of events or the time to the event. Finally, of 46 MMR patients who did not relapse, 35 had undetectable transcripts at last follow up. Positive Q-PCR had low specificity (19%) and positive predictive value (12%) in predicting relapse after allogeneic HSC transplantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Our data confirm that the detection of low levels of bcr-abl transcripts (as based on Q-PCR) has a poor accuracy in predicting relapse, and it should not be considered as the sole indication to start treatment. It appears that fluctuation of bcr-abl transcript levels is common as late as &gt; 10 yrs after transplant, possibly suggesting the long term persistence of CML stem cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Rosti: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy.</jats:p> </jats:sec>
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author Arpinati, Mario, Amabile, Marilina, Bochicchio, maria Teresa, Poerio, Angela, Bandini, Giuseppe, Bonifazi, Francesca, Stanzani, Marta, Castagnetti, Fausto, Rosti, Gianantonio, Martinelli, Giovanni, Baccarani, Michele
author_facet Arpinati, Mario, Amabile, Marilina, Bochicchio, maria Teresa, Poerio, Angela, Bandini, Giuseppe, Bonifazi, Francesca, Stanzani, Marta, Castagnetti, Fausto, Rosti, Gianantonio, Martinelli, Giovanni, Baccarani, Michele, Arpinati, Mario, Amabile, Marilina, Bochicchio, maria Teresa, Poerio, Angela, Bandini, Giuseppe, Bonifazi, Francesca, Stanzani, Marta, Castagnetti, Fausto, Rosti, Gianantonio, Martinelli, Giovanni, Baccarani, Michele
author_sort arpinati, mario
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description <jats:title>Abstract</jats:title> <jats:p>Abstract 1287</jats:p> <jats:sec> <jats:title>Background:</jats:title> <jats:p>Monitoring of minimal residual disease through RT-PCR analysis of bcr-abl transcripts allows early detection of CML relapse after allogeneic HSCT. However, the introduction of more sensitive techniques, such as quantitative PCR, may result in decreased specificity, leading to false positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods:</jats:title> <jats:p>In this study we reviewed the results of molecular analysis of bcr-abl transcripts in all patients with p210+ CML who underwent allogeneic HSCT from 1983 through 2007. Q-PCR analysis was started in 2002. Out of 189 patients, 87 patients had available Q-PCR data; of these, 63 patients with at least three separate Q-PCR data were included in the study. Median time to the 1st Q-PCR analysis was 2196 days (35-7823). Median age was 36 years (13-56), 62%/38% received transplant from a related/unrelated donor, 62% with BM. 32% were in accelerated phase (AP). Patients with at least one positive Q-PCR value (measured as a ratio of bcr-abl to abl of &gt; 0.001) were classified as Major Molecular Remission (MMR) patients. Each event was defined as one or more consecutive positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>60/63 patients are alive after a median follow up of 3693 days (898-9405). 6 have relapsed 2142 (1419-3746) days after transplant. 52 (83%) patients had at least one positive result (28 with a value of &gt;0.01, 24 with a value of &lt;0.01), whereas 11 (17%) had persistent undetectable transcripts. In MMR patients, 94 events occurred. 29 patients had only one event, while 6 had &gt;3 events. In 10 patients, the event occurred within 1 year after transplant, whereas in 28 it occurred after &gt;5 years. 6/52 MMR patients relapsed, as compared to 0/11 with persistent undetectable transcripts (p=0.19). Relapse did not correlate with the Q-PCR value, the number of events or the time to the event. Finally, of 46 MMR patients who did not relapse, 35 had undetectable transcripts at last follow up. Positive Q-PCR had low specificity (19%) and positive predictive value (12%) in predicting relapse after allogeneic HSC transplantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Our data confirm that the detection of low levels of bcr-abl transcripts (as based on Q-PCR) has a poor accuracy in predicting relapse, and it should not be considered as the sole indication to start treatment. It appears that fluctuation of bcr-abl transcript levels is common as late as &gt; 10 yrs after transplant, possibly suggesting the long term persistence of CML stem cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Rosti: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy.</jats:p> </jats:sec>
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spelling Arpinati, Mario Amabile, Marilina Bochicchio, maria Teresa Poerio, Angela Bandini, Giuseppe Bonifazi, Francesca Stanzani, Marta Castagnetti, Fausto Rosti, Gianantonio Martinelli, Giovanni Baccarani, Michele 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v116.21.1287.1287 <jats:title>Abstract</jats:title> <jats:p>Abstract 1287</jats:p> <jats:sec> <jats:title>Background:</jats:title> <jats:p>Monitoring of minimal residual disease through RT-PCR analysis of bcr-abl transcripts allows early detection of CML relapse after allogeneic HSCT. However, the introduction of more sensitive techniques, such as quantitative PCR, may result in decreased specificity, leading to false positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and methods:</jats:title> <jats:p>In this study we reviewed the results of molecular analysis of bcr-abl transcripts in all patients with p210+ CML who underwent allogeneic HSCT from 1983 through 2007. Q-PCR analysis was started in 2002. Out of 189 patients, 87 patients had available Q-PCR data; of these, 63 patients with at least three separate Q-PCR data were included in the study. Median time to the 1st Q-PCR analysis was 2196 days (35-7823). Median age was 36 years (13-56), 62%/38% received transplant from a related/unrelated donor, 62% with BM. 32% were in accelerated phase (AP). Patients with at least one positive Q-PCR value (measured as a ratio of bcr-abl to abl of &gt; 0.001) were classified as Major Molecular Remission (MMR) patients. Each event was defined as one or more consecutive positive results.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>60/63 patients are alive after a median follow up of 3693 days (898-9405). 6 have relapsed 2142 (1419-3746) days after transplant. 52 (83%) patients had at least one positive result (28 with a value of &gt;0.01, 24 with a value of &lt;0.01), whereas 11 (17%) had persistent undetectable transcripts. In MMR patients, 94 events occurred. 29 patients had only one event, while 6 had &gt;3 events. In 10 patients, the event occurred within 1 year after transplant, whereas in 28 it occurred after &gt;5 years. 6/52 MMR patients relapsed, as compared to 0/11 with persistent undetectable transcripts (p=0.19). Relapse did not correlate with the Q-PCR value, the number of events or the time to the event. Finally, of 46 MMR patients who did not relapse, 35 had undetectable transcripts at last follow up. Positive Q-PCR had low specificity (19%) and positive predictive value (12%) in predicting relapse after allogeneic HSC transplantation.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Our data confirm that the detection of low levels of bcr-abl transcripts (as based on Q-PCR) has a poor accuracy in predicting relapse, and it should not be considered as the sole indication to start treatment. It appears that fluctuation of bcr-abl transcript levels is common as late as &gt; 10 yrs after transplant, possibly suggesting the long term persistence of CML stem cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Disclosures:</jats:title> <jats:p>Rosti: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy.</jats:p> </jats:sec> Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT. Blood
spellingShingle Arpinati, Mario, Amabile, Marilina, Bochicchio, maria Teresa, Poerio, Angela, Bandini, Giuseppe, Bonifazi, Francesca, Stanzani, Marta, Castagnetti, Fausto, Rosti, Gianantonio, Martinelli, Giovanni, Baccarani, Michele, Blood, Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT., Cell Biology, Hematology, Immunology, Biochemistry
title Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_full Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_fullStr Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_full_unstemmed Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_short Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
title_sort long term study of the impact of quantitative molecular monitoring of bcr-abl transcripts on the risk of relapse of cml after allogeneic hsct.
title_unstemmed Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
topic Cell Biology, Hematology, Immunology, Biochemistry
url http://dx.doi.org/10.1182/blood.v116.21.1287.1287