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1. 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

Author

Pau Montesinos, Joaquín Díaz-Mediavilla, Guillermo Debén, Virginia Prates, Mar Tormo, Vicente Rubio, Inmaculada Pérez, Isolda Fernández, Maricruz Viguria, Chelo Rayón, José González, Javier de la Serna, Jordi Esteve, Juan M. Bergua, Concha Rivas, Marcos González, Jose D. González, Silvia Negri, Salut Brunet, Bob Lowenberg, and Miguel A. Sanz

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
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.

Published
2009
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2. 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

Author

Concha Rivas, José González, Marcos González, Miguel A. Sanz, Guillermo Deben, Jordi Esteve, Javier de la Serna, Pau Montesinos, Inmaculada Pérez, Salut Brunet, Isolda Fernández, Joaquín Díaz-Mediavilla, Chelo Rayon, Silvia Negri, Mar Tormo, José D. González, Vicente Rubio, Maricruz Viguria, Virginia Prates, Juan Bergua, Bob Löwenberg, Hematology, [Montesinos,P, Sanz, MA] Hospital Universitario La Fe, Valencia, Spain. [Díaz-Mediavilla,J] Hospital Clínico San Carlos, Madrid, Spain. [Debén,G] Hospital Juan Canalejo, La Coruña, Spain. [Prates,V] Instituto de Trasplante de Médula Ósea, Buenos Aires, Argentina. [Tormo,M] Hospital Clínico Universitario, Valencia, Spain. [Rubio,V] Hospital General, Jerez de la Frontera, Spain. [Pérez,I] Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Fernández,I] Fundaleu, Buenos Aires, Argentina. [Viguria,M] Hospital de Navarra, Pamplona, Spain. [Rayón,C] Hospital Central de Asturias, Oviedo, Spain. [González,J] Hospital Universitario Virgen del Rocío, Sevilla, Spain.[Serna,J de la] Hospital 12 de Octubre, Madrid, Spain. [Esteve,J] Hospital Clinic, Barcelona, Spain. [Bergua,JM] Hospital San Pedro de Alcántara, Cáceres, Spain. [Rivas,C] Hospital General, Alicante, Spain. [González,M] Hospital Universitario, Salamanca, Spain. [González,JD] Hospital Insular, Las Palmas, Spain. [Negri,S] Hospital Carlos Haya, Málaga, Spain. [Brunet,S] Hospital Sant Pau, Barcelona, Spain. [Lowenberg,B] Erasmus University Medical Center, Rotterdam, The Netherlands., and This study was supported in part by the Fundación para la Investigación hospital Universitario La Fe-Ayudas Bancaja (grant 2006/0137), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0031).

Subjects
Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Anthracyclines::Daunorubicin::Idarubicin [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings], Male, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], idarubicin, Gastroenterology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Central Nervous System Neoplasms, Leukemia, Promyelocytic, Acute, Recurrence, Risk Factors, Cumulative incidence, Antibiotics, Antineoplastic, Hematology, Middle Aged, all-trans retinoic acid, Leukemia, medicine.anatomical_structure, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Female, medicine.drug, Acute promyelocytic leukemia, Adult, central nervous system relapse, medicine.medical_specialty, Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [Medical Subject Headings], Anthracycline, Adolescent, Central nervous system, Check Tags::Male [Medical Subject Headings], Tretinoin, Neoplasias del sistema nervioso central, Central nervous system disease, Internal medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Idarubicin, Humans, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Letters to the Editor, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Acyclic::Alkenes::Polyenes::Carotenoids::Retinoids [Medical Subject Headings], Leucemia promielocítica aguda, Aged, Antibióticos antineoplásicos, business.industry, prognostic factors, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antibiotics, Antineoplastic [Medical Subject Headings], acute promyelocytic leukemia, medicine.disease, Surgery, Diseases::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], business
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.

Published
2009

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