Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin

Author:

de la Serna Javier1,Montesinos Pau1,Vellenga Edo2,Rayón Chelo3,Parody Ricardo4,León Angel5,Esteve Jordi6,Bergua Juan M.7,Milone Gustavo8,Debén Guillermo9,Rivas Concha10,González Marcos11,Tormo Mar12,Díaz-Mediavilla Joaquín13,González Jose D.14,Negri Silvia15,Amutio Elena16,Brunet Salut17,Lowenberg Bob18,Sanz Miguel A.19

Affiliation:

1. Hospital 12 de Octubre, Madrid, Spain;

2. University Hospital, Groningen, The Netherlands;

3. Hospital Central de Asturias, Oviedo, Spain;

4. Hospital Universitario Virgen del Rocío, Sevilla, Spain;

5. Hospital General, Jerez de la Frontera, Spain;

6. Hospital Clinic, Barcelona, Spain;

7. Hospital San Pedro de Alcántara, Cáceres, Spain;

8. Fundaleu, Buenos Aires, Argentina;

9. Hospital Juan Canalejo, La Coruña, Spain;

10. Hospital General, Alicante, Spain;

11. Hospital Universitario, Salamanca, Spain;

12. Hospital Clínico Universitario, Valencia, Spain;

13. Hospital Clínico San Carlos, Madrid, Spain;

14. Hospital Insular, Las Palmas, Spain;

15. Hospital Carlos Haya, Málaga, Spain;

16. Hospital de Cruces, Baracaldo, Spain;

17. Hospital Sant Pau, Barcelona, Spain; and

18. Erasmus University Medical Center, Rotterdam, The Netherlands

19. Hospital Universitario La Fe, Valencia, Spain;

Abstract

Abstract 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference24 articles.

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5. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy.;Mandelli;Blood,1997

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