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Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis.

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Date

2009-09

Authors

Montesinos, Pau
Díaz-Mediavilla, Joaquín
Debén, Guillermo
Prates, Virginia
Tormo, Mar
Rubio, Vicente
Pérez, Inmaculada
Fernández, Isolda
Viguria, Maricruz
Rayón, Chelo

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Ferrata Storti Foundation
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Abstract

BACKGROUND The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. DESIGN AND METHODS Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. RESULTS Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. CONCLUSIONS This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.

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Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't;

MeSH Terms

Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antibiotics, Antineoplastic
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Anthracyclines::Daunorubicin::Idarubicin
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Acyclic::Alkenes::Polyenes::Carotenoids::Retinoids
Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent

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Keywords

Acute promyelocytic leukemia, Central nervous system relapse, All-trans retinoic acid, Idarubicin, Prognostic factors, Neoplasias del sistema nervioso central, Antibióticos antineoplásicos, Leucemia promielocítica aguda

Citation

Montesinos P, Díaz-Mediavilla J, Debén G, Prates V, Tormo M, Rubio V, et al. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis. Haematologica. 2009; 94(9):1242-9