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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3395-3402.
Prepublished online as a Blood First Edition Paper on January 14, 2008; DOI 10.1182/blood-2007-07-100669.
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Submitted July 10, 2007
Accepted January 10, 2008
Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin
Javier de la Serna, Pau Montesinos, Edo Vellenga, Chelo Rayon, Ricardo Parody, Angel Leon, Jordi Esteve, Juan M Bergua, Gustavo Milone, Guillermo Deben, Concha Rivas, Marcos Gonzalez, Mar Tormo, Joaquin Diaz-Mediavilla, Jose D Gonzalez, Silvia Negri, Elena Amutio, Salut Brunet, Bob Lowenberg, and Miguel A. Sanz*
Hematology Service, Hospital 12 de Octubre, Madrid, Spain
Hematology Service, Hospital Universitario La Fe, Valencia, Spain
Hematology Department, University Hospital Groningen, Groningen, Netherlands
Hematology Service, Hospital Central de Asturias, Oviedo, Spain
Hematology Service, Hospital Universitario Virgen del Rocio, Sevilla, Spain
Hematology Service, Hospital General, Jerez de la Frontera, Spain
Hematology Service, Hospital Clinic, Barcelona, Spain
Hematology Service, Hospital San Pedro de Alcantara, Caceres, Spain
Hematology Service, Fundaleu, Buenos Aires, Argentina
Hematology Service, Hospital Juan Canalejo, La Coruna, Spain
Hematology Service, Hospital General, Alicante, Spain
Hematology Service, Hospital Universitario, Salamanca, Spain
Hematology Service, Hospital Clinico Universitario, Valencia, Spain
Hematology Service, Hospital Clinico San Carlos, Madrid, Spain
Hematology Service, Hospital Insular, Las Palmas, Spain
Hematology Service, Hospital Carlos Haya, Málaga, Spain
Hematology Service, Hospital de Cruces, Baracaldo, Spain
Hematology Service, Hospital Sant Pau, Barcelona, Spain
Hematology Department, Erasmus University Medical Center, Rotterdam, Netherlands
* Corresponding author; email: msanz{at}uv.es.
Understanding of the prognostic factors associated with the various forms of induction mortality in patients with acute promyelocytic leukemia (APL) has remained remarkably limited. This study reports the incidence, time of occurrence, and prognostic factors of the major categories of induction failure in a series of 732 newly diagnosed patients with APL of all ages (range, 2 to 83 years) who received ATRA plus idarubicin as induction therapy in two consecutive studies of the PETHEMA Group. Complete remission was attained in 666 patients (91%). All the 66 induction failures were due to induction death. Hemorrhage was the most common cause of induction death (5%), followed by infection (2.3%) and differentiation syndrome (1.4%). Multivariate analysis identified specific and distinct pretreatment characteristics to correlate with an increased risk of death caused by hemorrhage (abnormal creatinine level, increased peripheral blast counts, and presence of coagulopathy), infection (age > 60 years, male gender, and fever at presentation), and differentiation syndrome (ECOG score >1 and low albumin levels), respectively. These data furnish clinically relevant information that might be useful for designing more appropriately risk-adapted treatment protocols aimed at reducing the considerable problem of induction mortality in APL.
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