Risk-adapted treatment of acute promyelocytic leukemia: Results from the international consortium for childhood APL

Anna Maria Testi, Andrea Pession, Daniela Diverio, David Grimwade, Brenda Gibson, Amilcar Cardoso de Azevedo, Lorena Moran, Guy Leverger, Sarah Elitzur, Henrik Hasle, Jutte van der Werff ten Bosch, Owen Smith, Marisa de Rosa, Alfonso Piciocchi, Francesco Lo Coco, Robin Foà, Franco Locatelli, Gertjan J. L. Kaspers

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Abstract

Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 3 109/L or ‡10 3 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.
Original languageEnglish
Pages (from-to)405-412
JournalBlood
Volume132
Issue number4
DOIs
Publication statusPublished - 2018

Cite this

Testi, Anna Maria ; Pession, Andrea ; Diverio, Daniela ; Grimwade, David ; Gibson, Brenda ; Cardoso de Azevedo, Amilcar ; Moran, Lorena ; Leverger, Guy ; Elitzur, Sarah ; Hasle, Henrik ; van der Werff ten Bosch, Jutte ; Smith, Owen ; de Rosa, Marisa ; Piciocchi, Alfonso ; Lo Coco, Francesco ; Foà, Robin ; Locatelli, Franco ; Kaspers, Gertjan J. L. / Risk-adapted treatment of acute promyelocytic leukemia: Results from the international consortium for childhood APL. In: Blood. 2018 ; Vol. 132, No. 4. pp. 405-412.
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title = "Risk-adapted treatment of acute promyelocytic leukemia: Results from the international consortium for childhood APL",
abstract = "Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 3 109/L or ‡10 3 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97{\%} of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6{\%} and 79.9{\%}, respectively; they were 98.4{\%} and 89.4{\%} in SR patients and 84.3{\%} and 74.2{\%} in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.",
author = "Testi, {Anna Maria} and Andrea Pession and Daniela Diverio and David Grimwade and Brenda Gibson and {Cardoso de Azevedo}, Amilcar and Lorena Moran and Guy Leverger and Sarah Elitzur and Henrik Hasle and {van der Werff ten Bosch}, Jutte and Owen Smith and {de Rosa}, Marisa and Alfonso Piciocchi and {Lo Coco}, Francesco and Robin Fo{\`a} and Franco Locatelli and Kaspers, {Gertjan J. L.}",
year = "2018",
doi = "10.1182/blood-2018-03-836528",
language = "English",
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Testi, AM, Pession, A, Diverio, D, Grimwade, D, Gibson, B, Cardoso de Azevedo, A, Moran, L, Leverger, G, Elitzur, S, Hasle, H, van der Werff ten Bosch, J, Smith, O, de Rosa, M, Piciocchi, A, Lo Coco, F, Foà, R, Locatelli, F & Kaspers, GJL 2018, 'Risk-adapted treatment of acute promyelocytic leukemia: Results from the international consortium for childhood APL' Blood, vol. 132, no. 4, pp. 405-412. https://doi.org/10.1182/blood-2018-03-836528

Risk-adapted treatment of acute promyelocytic leukemia: Results from the international consortium for childhood APL. / Testi, Anna Maria; Pession, Andrea; Diverio, Daniela; Grimwade, David; Gibson, Brenda; Cardoso de Azevedo, Amilcar; Moran, Lorena; Leverger, Guy; Elitzur, Sarah; Hasle, Henrik; van der Werff ten Bosch, Jutte; Smith, Owen; de Rosa, Marisa; Piciocchi, Alfonso; Lo Coco, Francesco; Foà, Robin; Locatelli, Franco; Kaspers, Gertjan J. L.

In: Blood, Vol. 132, No. 4, 2018, p. 405-412.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Risk-adapted treatment of acute promyelocytic leukemia: Results from the international consortium for childhood APL

AU - Testi, Anna Maria

AU - Pession, Andrea

AU - Diverio, Daniela

AU - Grimwade, David

AU - Gibson, Brenda

AU - Cardoso de Azevedo, Amilcar

AU - Moran, Lorena

AU - Leverger, Guy

AU - Elitzur, Sarah

AU - Hasle, Henrik

AU - van der Werff ten Bosch, Jutte

AU - Smith, Owen

AU - de Rosa, Marisa

AU - Piciocchi, Alfonso

AU - Lo Coco, Francesco

AU - Foà, Robin

AU - Locatelli, Franco

AU - Kaspers, Gertjan J. L.

PY - 2018

Y1 - 2018

N2 - Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 3 109/L or ‡10 3 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.

AB - Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 3 109/L or ‡10 3 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/29789356

U2 - 10.1182/blood-2018-03-836528

DO - 10.1182/blood-2018-03-836528

M3 - Article

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SP - 405

EP - 412

JO - Blood

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SN - 0006-4971

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