Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL
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...
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| Veröffentlicht in: | Blood 2018-07, Vol.132 (4), p.405-412 |
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| creator | Testi, Anna Maria Pession, Andrea Diverio, Daniela Grimwade, David Gibson, Brenda de Azevedo, Amilcar Cardoso Moran, Lorena Leverger, Guy Elitzur, Sarah Hasle, Henrik ten Bosch, Jutte van der Werff Smith, Owen De Rosa, Marisa Piciocchi, Alfonso Lo Coco, Francesco Foà, Robin Locatelli, Franco Kaspers, Gertjan J.L. |
| description | 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 ( |
| doi_str_mv | 10.1182/blood-2018-03-836528 |
| format | Article |
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•Risk-adapted therapy allowed achieving remarkable cure rates in an international trial on childhood APL.•Reduction of the anthracycline cumulative dose coupled with ATRA extended use does not compromise the outcome of children with APL.
[Display omitted]</description><identifier>ISSN: 0006-4971</identifier><identifier>ISSN: 1528-0020</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2018-03-836528</identifier><identifier>PMID: 29789356</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Anthracyclines - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Child ; Child, Preschool ; Daunorubicin - administration & dosage ; Female ; Humans ; Idarubicin - administration & dosage ; Infant ; International Agencies ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - pathology ; Male ; Remission Induction ; Risk Factors ; Treatment Outcome ; Tretinoin - administration & dosage ; Young Adult</subject><ispartof>Blood, 2018-07, Vol.132 (4), p.405-412</ispartof><rights>2018 American Society of Hematology</rights><rights>2018 by The American Society of Hematology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-ea5e4f1bbece96d5f9b032f65373c71bfba342d7eca359da252c60775b5c485e3</citedby><cites>FETCH-LOGICAL-c408t-ea5e4f1bbece96d5f9b032f65373c71bfba342d7eca359da252c60775b5c485e3</cites><orcidid>0000-0002-0379-9562 ; 0000-0003-0494-7165 ; 0000-0002-1354-3659</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29789356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Testi, Anna Maria</creatorcontrib><creatorcontrib>Pession, Andrea</creatorcontrib><creatorcontrib>Diverio, Daniela</creatorcontrib><creatorcontrib>Grimwade, David</creatorcontrib><creatorcontrib>Gibson, Brenda</creatorcontrib><creatorcontrib>de Azevedo, Amilcar Cardoso</creatorcontrib><creatorcontrib>Moran, Lorena</creatorcontrib><creatorcontrib>Leverger, Guy</creatorcontrib><creatorcontrib>Elitzur, Sarah</creatorcontrib><creatorcontrib>Hasle, Henrik</creatorcontrib><creatorcontrib>ten Bosch, Jutte van der Werff</creatorcontrib><creatorcontrib>Smith, Owen</creatorcontrib><creatorcontrib>De Rosa, Marisa</creatorcontrib><creatorcontrib>Piciocchi, Alfonso</creatorcontrib><creatorcontrib>Lo Coco, Francesco</creatorcontrib><creatorcontrib>Foà, Robin</creatorcontrib><creatorcontrib>Locatelli, Franco</creatorcontrib><creatorcontrib>Kaspers, Gertjan J.L.</creatorcontrib><title>Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL</title><title>Blood</title><addtitle>Blood</addtitle><description>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 × 109/L or ≥10 × 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.
•Risk-adapted therapy allowed achieving remarkable cure rates in an international trial on childhood APL.•Reduction of the anthracycline cumulative dose coupled with ATRA extended use does not compromise the outcome of children with APL.
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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 × 109/L or ≥10 × 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.
•Risk-adapted therapy allowed achieving remarkable cure rates in an international trial on childhood APL.•Reduction of the anthracycline cumulative dose coupled with ATRA extended use does not compromise the outcome of children with APL.
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| subjects | Adolescent Adult Anthracyclines - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Child Child, Preschool Daunorubicin - administration & dosage Female Humans Idarubicin - administration & dosage Infant International Agencies Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - pathology Male Remission Induction Risk Factors Treatment Outcome Tretinoin - administration & dosage Young Adult |
| title | Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL |
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