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Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation
Authors:Iku Kamitani  Takeshi Saito  Hiroki Yokoyama  Aya Nakano  Hiroto Ishii  Susumu Tanoue  Daiki Hattori  Sayaka Oshima  Shoko Ishii  Tadahiro Gunji  Ryoko Fukushima  Atsushi Katsube  Takaki Shimada  Kaichi Nishiwaki  Nobuaki Dobashi  Shingo Yano
Affiliation:1. Division of Clinical Oncology/Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Japan;2. Division of Clinical Oncology/Hematology, The Jikei University Kashiwa Hospital, Japan;3. Division of Clinical Oncology/Hematology, The Jikei University Daisan Hospital, Japan;1. Department of Pediatrics, Wakayama Medical University, Wakayama City, Wakayama, Japan;2. Department of Medical Safety Promotion, Wakayama Medical University, Wakayama City, Wakayama, Japan;3. Department of Ophthalmology, Wakayama Medical University, Wakayama City, Wakayama, Japan;1. Department of Dermatology, Stanford University School of Medicine, Stanford, California;2. Department of Pathology, Stanford University School of Medicine, Stanford, California;3. Department of Pathology, University of Virginia School of Medicine, UVA Health System, Charlottesville, Virginia;4. Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California;1. Department of Dermatology, University of California, Irvine, California;2. Department of Dermatology, Brigham and Women''s Hospital, Boston, Massachusetts;3. Division of Hematology/Oncology, University of California, Irvine, California;1. School of Medicine, The University of Texas Medical Branch, Galveston, Texas;2. Department of Dermatology, The University of Texas Medical Branch, Galveston, Texas;1. University of Pennsylvania-Abramson Comprehensive Cancer Center, Philadelphia, PA, USA;2. Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA;3. MD Anderson Cancer Center, Houston, TX, USA;4. Department of Leukemia, University of California at San Francisco, San Francisco, CA, USA;5. Mayo Clinic, Rochester, MN, USA;6. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA;7. Penn State Milton S Hershey Medical Center, Hershey, PA, USA;8. Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA;9. Astellas Pharma Global Development, Northbrook, IL, USA;10. Hackensack University Medical Center, Hackensack, NJ, USA;11. Columbia University Medical Center, New York, NY, USA;12. Department of Medicine, University of Chicago, Chicago, IL, USA;13. Weill Cornell Medical College, New York, NY, USA;14. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;15. Virginia Cancer Specialists, Fairfax, VA, USA;p. Vanderbilt-Ingram Cancer Center, Nashville, TN, USA;q. Mayo Clinic, Scottsdale, AZ, USA;r. Department of Internal Medicine, Julius Maximilians University, Würzburg, Germany;s. Department of Internal Medicine, University of Minnesota, Minneapolis, MN, USA;t. Roswell Park Cancer Institute, Buffalo, NY, USA;u. Medical University of South Carolina-Hollings Cancer Center, Charleston, SC, USA;v. Department of Internal Medicine, Universitätsklinikum TU Dresden, Dresden, Germany;w. Department of Internal Medicine, Universitätsklinikum Giessen und Marburg, Marburg, Germany;x. “L e A Seragnoli”, University of Bologna, Bologna, Italy;y. Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
Abstract:The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 109/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but ‘stable disease’ status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.
Keywords:FLT3-ITD  Giltertinib  Transplantation
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