title: Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hematopoietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis.
abstract: OBJECTIVE
  Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain.
  
  
  METHODS
  We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning.
  
  
  RESULTS
  Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 × 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; ± standard deviation) was higher (30% ± 5% v 16% ± 5%; P = .006) and leukemia-free survival (LFS) lower (58% ± 5% v 71% ± 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR.
  
  
  CONCLUSIONS
  FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain. sbrunet@santpau.cat
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Jan
authors.initials: J
authors.lastname: Cornelissen
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.forename: Anna P
authors.initials: AP
authors.lastname: Iori
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3