Published online 16 July 2009
Haematologica, Vol 94, Issue 9, 1242-1249 doi:10.3324/haematol.2009.007872
Copyright © 2009 by Ferrata Storti Foundation
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Acute Promyelocytic Leukemia

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

Pau Montesinos1, Joaquín Díaz-Mediavilla2, Guillermo Debén3, Virginia Prates4, Mar Tormo5, Vicente Rubio6, Inmaculada Pérez7, Isolda Fernández8, Maricruz Viguria9, Chelo Rayón10, José González11, Javier de la Serna12, Jordi Esteve13, Juan M. Bergua14, Concha Rivas15, Marcos González16, Jose D. González17, Silvia Negri18, Salut Brunet19, Bob Lowenberg20, Miguel A. Sanz1

1 Hospital Universitario La Fe, Valencia, Spain
2 Hospital Clínico San Carlos, Madrid, Spain
3 Hospital Juan Canalejo, La Coruña, Spain
4 Instituto de Trasplante de Médula Ósea, Buenos Aires, Argentina
5 Hospital Clínico Universitario, Valencia, Spain
6 Hospital General, Jerez de la Frontera, Spain
7 Hospital Universitario Virgen de la Victoria, Málaga, Spain
8 Fundaleu, Buenos Aires, Argentina
9 Hospital de Navarra, Pamplona, Spain
10 Hospital Central de Asturias, Oviedo, Spain
11 Hospital Universitario Virgen del Rocío, Sevilla, Spain
12 Hospital 12 de Octubre, Madrid, Spain
13 Hospital Clinic, Barcelona, Spain
14 Hospital San Pedro de Alcántara, Cáceres, Spain
15 Hospital General, Alicante, Spain
16 Hospital Universitario, Salamanca, Spain
17 Hospital Insular, Las Palmas, Spain
18 Hospital Carlos Haya, Málaga, Spain
19 Hospital Sant Pau, Barcelona, Spain
20 Erasmus University Medical Center, Rotterdam, The Netherlands

Correspondence: Miguel A. Sanz, MD, PhD, Hematology Department, Hospital Universitario La Fe, Avda. Campanar 21, CP 46009, Valencia, Spain. E-mail:msanz{at}uv.es

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.

Key words: acute promyelocytic leukemia, central nervous system relapse, all-trans retinoic acid, idarubicin, prognostic factors.




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