Addressing the room for improvement in management of acute promyelocytic leukemia

Jan M. Nørgaard*, Lone S. Friis, Jørgen S. Kristensen, Marianne T. Severinsen, Ingolf Mølle, Claus W. Marcher, Peter Møller, Claudia Schoellkopf, Ove J. Nielsen, Birgitte S. Preiss, Mette K. Andersen, Eigil Kjeldsen, Bruno C. Medeiros, Lene S.G. Østgård, for the Danish Acute Leukemia Group

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population.

OBJECTIVES AND METHODS: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long-term clinical outcome in APL between 2000 and 2014.

RESULTS: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables.

CONCLUSIONS: The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Haematology
Vol/bind102
Udgave nummer6
Sider (fra-til)479-485
Antal sider7
ISSN0902-4441
DOI
StatusUdgivet - jun. 2019

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Acute Promyelocytic Leukemia
Clinical Trials
Leukemia
Mortality
Intracranial Hemorrhages
Disseminated Intravascular Coagulation
Tretinoin
Registries
Sepsis
Incidence
Therapeutics
Population

Citer dette

Nørgaard, J. M., Friis, L. S., Kristensen, J. S., Severinsen, M. T., Mølle, I., Marcher, C. W., ... for the Danish Acute Leukemia Group (2019). Addressing the room for improvement in management of acute promyelocytic leukemia. European Journal of Haematology, 102(6), 479-485. https://doi.org/10.1111/ejh.13229
Nørgaard, Jan M. ; Friis, Lone S. ; Kristensen, Jørgen S. ; Severinsen, Marianne T. ; Mølle, Ingolf ; Marcher, Claus W. ; Møller, Peter ; Schoellkopf, Claudia ; Nielsen, Ove J. ; Preiss, Birgitte S. ; Andersen, Mette K. ; Kjeldsen, Eigil ; Medeiros, Bruno C. ; Østgård, Lene S.G. ; for the Danish Acute Leukemia Group. / Addressing the room for improvement in management of acute promyelocytic leukemia. I: European Journal of Haematology. 2019 ; Bind 102, Nr. 6. s. 479-485.
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title = "Addressing the room for improvement in management of acute promyelocytic leukemia",
abstract = "Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population.OBJECTIVES AND METHODS: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long-term clinical outcome in APL between 2000 and 2014.RESULTS: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0{\%}, whereas clinical trial participants had an EDR of 6.7{\%}. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables.CONCLUSIONS: The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL.",
keywords = "acute promyelocytic leukemia, diagnostic awareness, early death, prognosis",
author = "N{\o}rgaard, {Jan M.} and Friis, {Lone S.} and Kristensen, {J{\o}rgen S.} and Severinsen, {Marianne T.} and Ingolf M{\o}lle and Marcher, {Claus W.} and Peter M{\o}ller and Claudia Schoellkopf and Nielsen, {Ove J.} and Preiss, {Birgitte S.} and Andersen, {Mette K.} and Eigil Kjeldsen and Medeiros, {Bruno C.} and {\O}stg{\aa}rd, {Lene S.G.} and {for the Danish Acute Leukemia Group}",
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Nørgaard, JM, Friis, LS, Kristensen, JS, Severinsen, MT, Mølle, I, Marcher, CW, Møller, P, Schoellkopf, C, Nielsen, OJ, Preiss, BS, Andersen, MK, Kjeldsen, E, Medeiros, BC, Østgård, LSG & for the Danish Acute Leukemia Group 2019, 'Addressing the room for improvement in management of acute promyelocytic leukemia', European Journal of Haematology, bind 102, nr. 6, s. 479-485. https://doi.org/10.1111/ejh.13229

Addressing the room for improvement in management of acute promyelocytic leukemia. / Nørgaard, Jan M.; Friis, Lone S.; Kristensen, Jørgen S.; Severinsen, Marianne T.; Mølle, Ingolf; Marcher, Claus W.; Møller, Peter; Schoellkopf, Claudia; Nielsen, Ove J.; Preiss, Birgitte S.; Andersen, Mette K.; Kjeldsen, Eigil; Medeiros, Bruno C.; Østgård, Lene S.G.; for the Danish Acute Leukemia Group.

I: European Journal of Haematology, Bind 102, Nr. 6, 06.2019, s. 479-485.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Addressing the room for improvement in management of acute promyelocytic leukemia

AU - Nørgaard, Jan M.

AU - Friis, Lone S.

AU - Kristensen, Jørgen S.

AU - Severinsen, Marianne T.

AU - Mølle, Ingolf

AU - Marcher, Claus W.

AU - Møller, Peter

AU - Schoellkopf, Claudia

AU - Nielsen, Ove J.

AU - Preiss, Birgitte S.

AU - Andersen, Mette K.

AU - Kjeldsen, Eigil

AU - Medeiros, Bruno C.

AU - Østgård, Lene S.G.

AU - for the Danish Acute Leukemia Group

N1 - © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2019/6

Y1 - 2019/6

N2 - Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population.OBJECTIVES AND METHODS: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long-term clinical outcome in APL between 2000 and 2014.RESULTS: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables.CONCLUSIONS: The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL.

AB - Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population.OBJECTIVES AND METHODS: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long-term clinical outcome in APL between 2000 and 2014.RESULTS: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables.CONCLUSIONS: The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL.

KW - acute promyelocytic leukemia

KW - diagnostic awareness

KW - early death

KW - prognosis

U2 - 10.1111/ejh.13229

DO - 10.1111/ejh.13229

M3 - Journal article

VL - 102

SP - 479

EP - 485

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 6

ER -