Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy.

Research output: Contribution to journalArticle

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Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy. / Grimwade, D; Jovanovic, JV; Hills, RK; Nugent, EA; Patel, Y; Flora, R; Diverio, D; Jones, K; Aslett, H; Batson, E; Rennie, K; Angell, R; Clark, RE; Solomon, E; Lo-Coco, F; Wheatley, Keith; Burnett, AK.

In: Journal of Clinical Oncology, 08.06.2009.

Research output: Contribution to journalArticle

Harvard

Grimwade, D, Jovanovic, JV, Hills, RK, Nugent, EA, Patel, Y, Flora, R, Diverio, D, Jones, K, Aslett, H, Batson, E, Rennie, K, Angell, R, Clark, RE, Solomon, E, Lo-Coco, F, Wheatley, K & Burnett, AK 2009, 'Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy.', Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2008.20.1533

APA

Grimwade, D., Jovanovic, JV., Hills, RK., Nugent, EA., Patel, Y., Flora, R., Diverio, D., Jones, K., Aslett, H., Batson, E., Rennie, K., Angell, R., Clark, RE., Solomon, E., Lo-Coco, F., Wheatley, K., & Burnett, AK. (2009). Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2008.20.1533

Vancouver

Author

Grimwade, D ; Jovanovic, JV ; Hills, RK ; Nugent, EA ; Patel, Y ; Flora, R ; Diverio, D ; Jones, K ; Aslett, H ; Batson, E ; Rennie, K ; Angell, R ; Clark, RE ; Solomon, E ; Lo-Coco, F ; Wheatley, Keith ; Burnett, AK. / Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy. In: Journal of Clinical Oncology. 2009.

Bibtex

@article{bcd13e4686cf4be58f54b7b61d953427,
title = "Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy.",
abstract = "PURPOSE: Molecular diagnostics and early assessment of treatment response that use methodologies capable of detecting submicroscopic disease can distinguish subgroups of patients with leukemia at differing relapse risk. Such information is being incorporated into risk-stratified protocols; however, there are few data concerning prospective use of sequential minimal residual disease (MRD) monitoring to identify more precisely those patients destined to experience relapse, which would allow more tailored therapies. METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) assays to detect leukemia-specific transcripts (ie, PML-RARA, RARA-PML) were used to prospectively analyze 6,727 serial blood and marrow samples from 406 patients with newly diagnosed acute promyelocytic leukemia (APL) who were receiving all-trans-retinoic acid and anthracycline-based chemotherapy. RESULTS: MRD monitoring according to the recommended schedule successfully identified the majority of patients subject to relapse and provided the most powerful predictor of relapse-free survival (RFS) in multivariable analysis (hazard ratio, 17.87; 95% CI, 6.88 to 46.41; P <.0001); MRD monitoring was far superior to presenting WBC (hazard ratio, 1.02; 95% CI, 1.00 to 1.03; P = .02), which is currently widely used to guide therapy. In patients who were predicted to experience relapse on the basis of MRD monitoring, early treatment intervention with arsenic trioxide prevented progression to overt relapse in the majority, and the RFS rate at 1 year from molecular relapse was 73%. By using this strategy, 3-year cumulative incidence of clinical relapse was only 5% in the Medical Research Council AML15 trial. CONCLUSION: Rigorous sequential RQ-PCR monitoring provides the strongest predictor of RFS in APL and, when coupled with pre-emptive therapy, provides a valid strategy to reduce rates of clinical relapse. This provides a model for development of a more individualized approach to management of other molecularly defined subtypes of acute leukemia.",
author = "D Grimwade and JV Jovanovic and RK Hills and EA Nugent and Y Patel and R Flora and D Diverio and K Jones and H Aslett and E Batson and K Rennie and R Angell and RE Clark and E Solomon and F Lo-Coco and Keith Wheatley and AK Burnett",
year = "2009",
month = jun,
day = "8",
doi = "10.1200/JCO.2008.20.1533",
language = "English",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",

}

RIS

TY - JOUR

T1 - Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy.

AU - Grimwade, D

AU - Jovanovic, JV

AU - Hills, RK

AU - Nugent, EA

AU - Patel, Y

AU - Flora, R

AU - Diverio, D

AU - Jones, K

AU - Aslett, H

AU - Batson, E

AU - Rennie, K

AU - Angell, R

AU - Clark, RE

AU - Solomon, E

AU - Lo-Coco, F

AU - Wheatley, Keith

AU - Burnett, AK

PY - 2009/6/8

Y1 - 2009/6/8

N2 - PURPOSE: Molecular diagnostics and early assessment of treatment response that use methodologies capable of detecting submicroscopic disease can distinguish subgroups of patients with leukemia at differing relapse risk. Such information is being incorporated into risk-stratified protocols; however, there are few data concerning prospective use of sequential minimal residual disease (MRD) monitoring to identify more precisely those patients destined to experience relapse, which would allow more tailored therapies. METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) assays to detect leukemia-specific transcripts (ie, PML-RARA, RARA-PML) were used to prospectively analyze 6,727 serial blood and marrow samples from 406 patients with newly diagnosed acute promyelocytic leukemia (APL) who were receiving all-trans-retinoic acid and anthracycline-based chemotherapy. RESULTS: MRD monitoring according to the recommended schedule successfully identified the majority of patients subject to relapse and provided the most powerful predictor of relapse-free survival (RFS) in multivariable analysis (hazard ratio, 17.87; 95% CI, 6.88 to 46.41; P <.0001); MRD monitoring was far superior to presenting WBC (hazard ratio, 1.02; 95% CI, 1.00 to 1.03; P = .02), which is currently widely used to guide therapy. In patients who were predicted to experience relapse on the basis of MRD monitoring, early treatment intervention with arsenic trioxide prevented progression to overt relapse in the majority, and the RFS rate at 1 year from molecular relapse was 73%. By using this strategy, 3-year cumulative incidence of clinical relapse was only 5% in the Medical Research Council AML15 trial. CONCLUSION: Rigorous sequential RQ-PCR monitoring provides the strongest predictor of RFS in APL and, when coupled with pre-emptive therapy, provides a valid strategy to reduce rates of clinical relapse. This provides a model for development of a more individualized approach to management of other molecularly defined subtypes of acute leukemia.

AB - PURPOSE: Molecular diagnostics and early assessment of treatment response that use methodologies capable of detecting submicroscopic disease can distinguish subgroups of patients with leukemia at differing relapse risk. Such information is being incorporated into risk-stratified protocols; however, there are few data concerning prospective use of sequential minimal residual disease (MRD) monitoring to identify more precisely those patients destined to experience relapse, which would allow more tailored therapies. METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) assays to detect leukemia-specific transcripts (ie, PML-RARA, RARA-PML) were used to prospectively analyze 6,727 serial blood and marrow samples from 406 patients with newly diagnosed acute promyelocytic leukemia (APL) who were receiving all-trans-retinoic acid and anthracycline-based chemotherapy. RESULTS: MRD monitoring according to the recommended schedule successfully identified the majority of patients subject to relapse and provided the most powerful predictor of relapse-free survival (RFS) in multivariable analysis (hazard ratio, 17.87; 95% CI, 6.88 to 46.41; P <.0001); MRD monitoring was far superior to presenting WBC (hazard ratio, 1.02; 95% CI, 1.00 to 1.03; P = .02), which is currently widely used to guide therapy. In patients who were predicted to experience relapse on the basis of MRD monitoring, early treatment intervention with arsenic trioxide prevented progression to overt relapse in the majority, and the RFS rate at 1 year from molecular relapse was 73%. By using this strategy, 3-year cumulative incidence of clinical relapse was only 5% in the Medical Research Council AML15 trial. CONCLUSION: Rigorous sequential RQ-PCR monitoring provides the strongest predictor of RFS in APL and, when coupled with pre-emptive therapy, provides a valid strategy to reduce rates of clinical relapse. This provides a model for development of a more individualized approach to management of other molecularly defined subtypes of acute leukemia.

U2 - 10.1200/JCO.2008.20.1533

DO - 10.1200/JCO.2008.20.1533

M3 - Article

C2 - 19506161

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

ER -