TY - JOUR
T1 - Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors
AU - Montesinos, Pau
AU - Bergua, Juan M.
AU - Vellenga, Edo
AU - Rayón, Chelo
AU - Parody, Ricardo
AU - De La Serna, Javier
AU - León, Angel
AU - Esteve, Jordi
AU - Milone, Gustavo
AU - Debén, Guillermo
AU - Rivas, Concha
AU - González, Marcos
AU - Tormo, Mar
AU - Joaquín, Díaz Mediavilla
AU - González, Jose D.
AU - Negri, Silvia
AU - Amutio, Elena
AU - Brunet, Salut
AU - Lowenberg, Bob
AU - Sanz, Miguel A.
PY - 2009/1/22
Y1 - 2009/1/22
N2 - Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- acteristics, prognostic factors, and out- come of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Espanol de Tratamientos en Hematologíc [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) ex- perienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 109/L and an abnor- mal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic pred- nisone prophylaxis (LPA99 trial) in con- trast to those receiving selective prophy- laxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Pa- tients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial. © 2009 by The American Society of Hematology.
AB - Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- acteristics, prognostic factors, and out- come of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Espanol de Tratamientos en Hematologíc [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) ex- perienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 109/L and an abnor- mal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic pred- nisone prophylaxis (LPA99 trial) in con- trast to those receiving selective prophy- laxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Pa- tients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial. © 2009 by The American Society of Hematology.
U2 - 10.1182/blood-2008-07-168617
DO - 10.1182/blood-2008-07-168617
M3 - Review article
SN - 0006-4971
VL - 113
SP - 775
EP - 783
JO - Blood
JF - Blood
IS - 4
ER -