Cited by 363Retinoids in leukemia and cellular processesAcute Myeloid Leukemia ResearchAcute Lymphoblastic Leukemia research

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Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors

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Montesinos, Pau, Bergua, Juan M., Vellenga, Edo, Rayón, Chelo, Parody, Ricardo, de la Serna, Javier, León, Angel, Esteve, Jordi, Milone, Gustavo, Debén, Guillermo, Rivas, Concha, González, Marcos, Tormo, Mar, Díaz-Mediavilla, Joaquín, González, Jose D., Negri, Silvia, Amutio, Elena, Brunet, Salut, Lowenberg, Bob, Sanz, Miguel A.·2009·Blood

DOI 10.1182/blood-2008-07-168617

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Abstract

Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 × 109/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).

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Authors: Montesinos, P., Bergua, J. M., Vellenga, E., Rayón, C., Parody, R., de la Serna, J., León, A., Esteve, J., Milone, G., Debén, G., Rivas, C., González, M., Tormo, M., Díaz-Mediavilla, J., González, J. D., Negri, S., Amutio, E., Brunet, S., Lowenberg, B., & Sanz, M. A.
Affiliations: Universitat Autònoma de Barcelona (ES)
Hospital San Pedro de Alcántara (ES)
University Medical Center Groningen (NL)
Hospital Universitario Central de Asturias (ES)
Hospital Universitario Virgen del Rocío (ES)
Hospital 12 de Octubre, Madrid, Spain;
Hospital General, Jerez de la Frontera, Spain;
Hospital Clínic de Barcelona (ES)
Fundaleu, Buenos Aires, Argentina;
Hospital Juan Canalejo, La Coruña, Spain;
Hospital General Universitario de Alicante Doctor Balmis (ES)
Hospital Universitario, Salamanca, Spain;
Hospital Clínico Universitario de Valencia (ES)
Hospital Clínico San Carlos, Madrid, Spain;
Hospital Insular, Las Palmas, Spain;
Hospital Carlos Haya, Málaga, Spain;
Hospital de Cruces (ES)
Hospital de Sant Pau (ES)
Erasmus University Medical Center, Rotterdam, The Netherlands
Hospital Universitario La Fe, Valencia, Spain;
ORCID: Montesinos, Pau
Bergua, Juan M.
Vellenga, Edo
Esteve, Jordi
González, Marcos
Tormo, Mar
Negri, Silvia
Brunet, Salut
Venue: Blood
Publisher: American Society of Hematology
Published: 2009-01-22
Volume: 113
Issue: 4
Pages: 775-783
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2008-07-168617
OpenAlex: W1982745688
Cited by: 362
References: 42
Citations by year: 2026: 19 · 2025: 22 · 2024: 31 · 2023: 23 · 2022: 21 · 2021: 33 · 2020: 33 · 2019: 22 · 2018: 23 · 2017: 19 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 8 · 2012: 11
FWCI: 6.58
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
Keywords: differentiation syndrome, acute promyelocytic leukemia, all-trans retinoic acid, idarubicin, anthracycline chemotherapy, prognostic factors, mortality, relapse-free survival, dexamethasone prophylaxis, serum creatinine, white blood cell count
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prognosis, Recurrence, Risk Factors, Syndrome, Time Factors, Tretinoin, Leukemia, Promyelocytic, Acute, Disease-Free Survival, Anthracyclines

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Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors

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