title: The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia.
abstract: FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD-positive AML compared with what has been reported in those treated with chemotherapy alone.
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Tal
authors.initials: T
authors.lastname: Schechter
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Gassas
authors.affiliation: Department of Biostatistics Vanderbilt University, Nashville, Tennessee.
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pollard
authors.affiliation: Department of Pediatrics, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.affiliation: Department of Pediatrics, Rambam Medical Center, Haifa, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Zaidman
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Johann
authors.initials: J
authors.lastname: Hitzler
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelhaleem
authors.affiliation: Division of Pediatric Hematology/Oncology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennesee.
authors.forename: Richard
authors.initials: R
authors.lastname: Ho
authors.affiliation: Division of Pediatric Hematology/Oncology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennesee.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Domm
authors.affiliation: Department of Pediatrics, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.affiliation: Division of Pediatric Hematology/Oncology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennesee. Electronic address: Haydar.Frangoul@vanderbilt.edu.
authors.forename: Haydar
authors.initials: H
authors.lastname: Frangoul
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D058674:Chromosome Duplication; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014916:Whole-Body Irradiation; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myelogenous leukemia; Children; FLT3 internal tandem duplication (FLT3/ITD)