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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.
CLINICAL TRIALS AND OBSERVATIONS Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin1 Hospital 12 de Octubre, Madrid, Spain; 2 Hospital Universitario La Fe, Valencia, Spain; 3 University Hospital, Groningen, The Netherlands; 4 Hospital Central de Asturias, Oviedo, Spain; 5 Hospital Universitario Virgen del Rocío, Sevilla, Spain; 6 Hospital General, Jerez de la Frontera, Spain; 7 Hospital Clinic, Barcelona, Spain; 8 Hospital San Pedro de Alcántara, Cáceres, Spain; 9 Fundaleu, Buenos Aires, Argentina; 10 Hospital Juan Canalejo, La Coruña, Spain; 11 Hospital General, Alicante, Spain; 12 Hospital Universitario, Salamanca, Spain; 13 Hospital Clínico Universitario, Valencia, Spain; 14 Hospital Clínico San Carlos, Madrid, Spain; 15 Hospital Insular, Las Palmas, Spain; 16 Hospital Carlos Haya, Málaga, Spain; 17 Hospital de Cruces, Baracaldo, Spain; 18 Hospital Sant Pau, Barcelona, Spain; and 19 Erasmus University Medical Center, Rotterdam, The Netherlands An 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 patients of all ages (range, 2-83 years) with newly diagnosed APL who received all-trans retinoic acid (ATRA) plus idarubicin as induction therapy in 2 consecutive studies of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (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 sex, and fever at presentation), and differentiation syndrome (Eastern Cooperative Oncology Group [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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| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||