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

Fecha de publicación: 01/09/2009

Autores de IIS La Fe

Pau Montesinos Fernández

Autor
Miguel Ángel Sanz Alonso

Autor

Participantes ajenos a IIS La Fe

Diaz-Mediavilla, Joaquin
Deben, Guillermo
Prates, Virginia
Tormo, Mar
Rubio, Vicente
Perez, Inmaculada
Fernandez, Isolda
Viguria, Maricruz
Rayon, Chelo
Gonzalez, Jose
de la Serna, Javier
Esteve, Jordi
Bergua, Juan M.
Rivas, Concha
Gonzalez, Marcos
Gonzalez, Jose D.
Negri, Silvia
Brunet, Salut
Lowenberg, Bob

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

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.