Sorafenib Therapy for Pediatric Acute Myeloid Leukemia with FMS-like Tyrosine Kinase 3-internal Tandem Duplication Mutations: 2 Case Reports

Published on May 1, 2017in Journal of Pediatric Hematology Oncology1.289
路 DOI :10.1097/MPH.0000000000000672
Shinya Osone12
Estimated H-index: 12
,
Toshihiko Imamura23
Estimated H-index: 23
+ 9 AuthorsHajime Hosoi31
Estimated H-index: 31
Source
Abstract
Sorafenib is a promising agent for treating pediatric refractory acute myeloid leukemia (AML) exhibiting FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD); however, its optimal use needs to be established. We report 2 cases of refractory pediatric FLT3-ITD-positive AML treated with sorafenib. Case 1 underwent stem cell transplantation (SCT) without entering remission, despite the use of chemotherapy. This patient relapsed despite receiving post-SCT sorafenib. Chemotherapy combined with sorafenib successfully achieved complete remission in case 2. This patient received post-SCT sorafenib and remains in complete remission. The combination of pre-SCT and post-SCT sorafenib may thus be effective for pediatric refractory FLT3-ITD-positive AML.
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References14
Newest
#1C. Michel Zwaan (EUR: Erasmus University Rotterdam)H-Index: 20
#2Edward A. Kolb (DuPont)H-Index: 7
Last. Gertjan J.L. KaspersH-Index: 77
view all 23 authors...
Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worl...
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#1Katherine Tarlock (Boston Children's Hospital)H-Index: 11
#2Bill H. Chang (OHSU: Oregon Health & Science University)H-Index: 28
Last. Jessica A. Pollard (Maine Medical Center)H-Index: 19
view all 18 authors...
Background FLT3/ITD is associated with poor outcomes in adult and pediatric acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) can improve cure rates, however relapse is still common. Recent studies demonstrate the activity of FLT3 inhibitors, including sorafenib, in targeting the underlying mutation. Procedure We conducted a retrospective study of 15 pediatric patients with FLT3/ITD+ AML treated with sorafenib within 18 months after receiving HSCT. Sorafenib...
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#1Yi-Bin Chen (Harvard University)H-Index: 28
#2Shuli Li (Harvard University)H-Index: 27
Last. Robert J. Soiffer (Harvard University)H-Index: 127
view all 22 authors...
Abstract The fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation is associated with a high relapse rate for patients with acute myeloid leukemia (AML) even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is a tyrosine kinase inhibitor, which inhibits the FLT3 tyrosine kinase and has shown encouraging activity in FLT3-ITD AML. We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML (ClinicalTrials.gov NCT0139...
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#1Mitsuru Miyachi (Kyoto Prefectural University of Medicine)H-Index: 12
#2Eri Watanabe (UTokyo: University of Tokyo)H-Index: 8
Last. Hajime Hosoi (Kyoto Prefectural University of Medicine)H-Index: 31
view all 9 authors...
Loss of mismatched HLA is a cause of relapse following HLA-mismatched allo-SCT. We directly detected the loss of mismatched HLA alleles in relapsed leukemic cells at a MRD level using HLA typing by multicolor FACS (HLA-Flow) in combination with FISH in the BM of two patients with MLL-AF9-positive AML, at 6 and 10聽months after mismatched allo-SCT. HLA-Flow with FISH analysis detected relapsed leukemic cells not expressing a mismatched HLA allele and harboring the MLL rearrangement. Simultaneously...
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#1Sharyn D. Baker (St. Jude Children's Research Hospital)H-Index: 74
#2Eric I. Zimmerman (St. Jude Children's Research Hospital)H-Index: 15
Last. Hiroto Inaba (St. Jude Children's Research Hospital)H-Index: 37
view all 13 authors...
Purpose: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment. Experimental Design: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate...
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#1Daisuke Tomizawa (Tokyo Medical and Dental University)H-Index: 29
#2Akio TawaH-Index: 27
Last. Souichi Adachi (Kyoto University)H-Index: 42
view all 20 authors...
Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children
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#1Michael R. Grunwald (Johns Hopkins University)H-Index: 13
#2Mark J. Levis (Johns Hopkins University)H-Index: 76
Since the Food and Drug Administration approval of imatinib for treatment of chronic myeloid leukemia in 2001, tyrosine kinase inhibitors (TKIs) have become a mainstay in the care of many malignancies. In acute myeloid leukemia (AML), activating mutations in the FMS-like tyrosine kinase 3 (FLT3) gene result in survival and proliferation of leukemic blasts and are associated with adverse prognosis. Therefore, the FLT3 receptor is an appealing target for inhibition. Multiple small molecule TKIs ar...
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#1Hiroto Inaba (St. Jude Children's Research Hospital)H-Index: 37
#2Jeffrey E. RubnitzH-Index: 90
Last. Sharyn D. BakerH-Index: 74
view all 15 authors...
Purpose To assess the toxicity, pharmacokinetics, and pharmacodynamics of multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in children with relapsed/refractory leukemia. Patients and Methods Twelve patients with acute leukemia (11 with acute myeloid leukemia [AML]) received sorafenib on days 1 to 7 and then concurrently with cytarabine (1 g/m2) and clofarabine (stratum one: 40 mg/m2, n = 10; stratum two [recent transplantation or fungal infection]: 20 mg/m2, n = 2) ...
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#1Shuiying Hu (St. Jude Children's Research Hospital)H-Index: 30
#2Hongmei NiuH-Index: 2
Last. Sharyn D. BakerH-Index: 74
view all 14 authors...
null mice was determined by pharmacokinetic studies using high performance liquid chromatography with tandem mass spectrometric detection, and steadystate concentrations were estimated by the fit of a one-compartment pharmacokinetic model to concentration鈥 time data. The antitumor activity of sorafenib alone (60 mg/kg) twice daily, cytarabine alone (6.25 mg/kg administered intraperitoneally), or sorafenib once or twice daily plus cytarabine was evaluated in NOD-SCIDIL2Rg null mice bearing AML xe...
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#1Hisayuki Yokoyama (Tohoku University)H-Index: 17
#2Andreas Lundqvist (NIH: National Institutes of Health)H-Index: 34
Last. Richard Childs (NIH: National Institutes of Health)H-Index: 73
view all 4 authors...
To the editor: We read with interest the article by Metzelder et al showing sorafenib had antileukemic activity and could be given safely to patients with FLT-3 mutated AML relapsing after allogeneic stem cell transplantation (ASCT).1 Because sorafenib delays progression of renal cell carcinoma, we administered this drug to patients who had progression of metastatic kidney cancer after an ASCT. Besides the classic sorafenib hand-foot syndrome, we also observed new-onset, biopsy-confirmed chronic...
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Cited By1
Newest
#1Arkadiusz Z. Dudek (HealthPartners)H-Index: 38
#2Kate A BaxstromH-Index: 1
Last. Maya Viner (UIC: University of Illinois at Chicago)H-Index: 2
view all 10 authors...
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