BACKGROUND: FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL). PROCEDURE: Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n = 50). RESULTS: Forty-two of the 104 patients (40%) had either FLT3/ITD (n = 28, 27%) or FLT3/ALM (n = 15, 14%). Median diagnostic WBC count was 23,400 cells/µl vs. 3,600 cells/µl for those with and without FLT3/Mut (P < 0.001), and similar results for the cohort of 50 patients treated on C9710 (P < 0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P = 0.004), microgranular variant histology (P = 0.035), and a lower remission rate (P = 0.009). In patients who received ATRA (C9710 or CCG-2911, n = 8), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P = 0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WT patients (47% vs. 0%, P = 0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy. CONCLUSIONS: FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease.
BACKGROUND:FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL). PROCEDURE: Diagnostic specimens from 104 pediatric APLpatients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n = 50). RESULTS: Forty-two of the 104 patients (40%) had either FLT3/ITD (n = 28, 27%) or FLT3/ALM (n = 15, 14%). Median diagnostic WBC count was 23,400 cells/µl vs. 3,600 cells/µl for those with and without FLT3/Mut (P < 0.001), and similar results for the cohort of 50 patients treated on C9710 (P < 0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P = 0.004), microgranular variant histology (P = 0.035), and a lower remission rate (P = 0.009). In patients who received ATRA (C9710 or CCG-2911, n = 8), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WTpatients (P = 0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WTpatients (47% vs. 0%, P = 0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy. CONCLUSIONS:FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APLpatients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease.
Authors: Michelle M Le Beau; Elizabeth M Davis; Bhumi Patel; Vernon T Phan; Jastinder Sohal; Scott C Kogan Journal: Blood Date: 2003-04-10 Impact factor: 22.113
Authors: Christian Thiede; Christine Steudel; Brigitte Mohr; Markus Schaich; Ulrike Schäkel; Uwe Platzbecker; Martin Wermke; Martin Bornhäuser; Markus Ritter; Andreas Neubauer; Gerhard Ehninger; Thomas Illmer Journal: Blood Date: 2002-06-15 Impact factor: 22.113
Authors: Y Yamamoto; H Kiyoi; Y Nakano; R Suzuki; Y Kodera; S Miyawaki; N Asou; K Kuriyama; F Yagasaki; C Shimazaki; H Akiyama; K Saito; M Nishimura; T Motoji; K Shinagawa; A Takeshita; H Saito; R Ueda; R Ohno; T Naoe Journal: Blood Date: 2001-04-15 Impact factor: 22.113
Authors: Bayard L Powell; Barry Moser; Wendy Stock; Robert E Gallagher; Cheryl L Willman; Richard M Stone; Jacob M Rowe; Steven Coutre; James H Feusner; John Gregory; Stephen Couban; Frederick R Appelbaum; Martin S Tallman; Richard A Larson Journal: Blood Date: 2010-08-12 Impact factor: 22.113
Authors: P D Kottaridis; R E Gale; M E Frew; G Harrison; S E Langabeer; A A Belton; H Walker; K Wheatley; D T Bowen; A K Burnett; A H Goldstone; D C Linch Journal: Blood Date: 2001-09-15 Impact factor: 22.113
Authors: M A Sanz; F Lo Coco; G Martín; G Avvisati; C Rayón; T Barbui; J Díaz-Mediavilla; G Fioritoni; J D González; V Liso; J Esteve; F Ferrara; P Bolufer; C Bernasconi; M Gonzalez; F Rodeghiero; D Colomer; M C Petti; J M Ribera; F Mandelli Journal: Blood Date: 2000-08-15 Impact factor: 22.113
Authors: Wing Y Au; Alvin Fung; Chor S Chim; Albert K Lie; Raymond Liang; Edmond S K Ma; Cheuk H Chan; Kit F Wong; Yok L Kwong Journal: Br J Haematol Date: 2004-05 Impact factor: 6.998
Authors: Louise M Kelly; Jeffrey L Kutok; Ifor R Williams; Christina L Boulton; Sonia M Amaral; David P Curley; Timothy J Ley; D Gary Gilliland Journal: Proc Natl Acad Sci U S A Date: 2002-06-11 Impact factor: 11.205
Authors: Fabiana Ostronoff; Megan Othus; Robert B Gerbing; Michael R Loken; Susana C Raimondi; Betsy A Hirsch; Beverly J Lange; Stephen Petersdorf; Jerald Radich; Frederick R Appelbaum; Alan S Gamis; Todd A Alonzo; Soheil Meshinchi Journal: Blood Date: 2014-08-21 Impact factor: 22.113
Authors: L Zhang; A Samad; M S Pombo-de-Oliveira; G Scelo; M T Smith; J Feusner; J L Wiemels; C Metayer Journal: Blood Rev Date: 2014-09-30 Impact factor: 8.250
Authors: Xavier Poiré; Barry K Moser; Robert E Gallagher; Kristina Laumann; Clara D Bloomfield; Bayard L Powell; Gregory Koval; Kabir Gulati; Nicholas Holowka; Richard A Larson; Martin S Tallman; Frederick R Appelbaum; Dorie Sher; Cheryl Willman; Elisabeth Paietta; Wendy Stock Journal: Leuk Lymphoma Date: 2014-02-04
Authors: Marianna Greco; Giovanni Caocci; Antonio Ledda; Adriana Vacca; Marcella Arras; Ivana Celeghini; Giorgio La Nasa Journal: Case Rep Hematol Date: 2013-07-07
Authors: Anna Maria Testi; Mariella D'Angiò; Franco Locatelli; Andrea Pession; Francesco Lo Coco Journal: Mediterr J Hematol Infect Dis Date: 2014-04-15 Impact factor: 2.576