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Value and pitfalls of assessing bone marrow morphologic findings to predict response in patients with myelofibrosis who undergo hematopoietic stem cell transplantation
Affiliation:1. Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;2. Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;3. Department of Pathology and the Hematological Malignancies Program, St. Jude Children''s Research Hospital, Memphis, TN, USA;1. Department of Otolaryngology-Head and Neck Surgery, University of Missouri, Columbia, MO, USA;2. Department of Biochemistry, University of Missouri, Columbia, MO, USA;3. Department of Bond Life Sciences Center, University of Missouri, Columbia, MO, USA;4. School of Dentistry and Department of Dermatology, University of Utah, Salt Lake City, UT, USA;1. Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA;2. University of Alabama at Birmingham, 619 19th St S, Birmingham, AL 35233, USA;3. Penn State Health Milton S. Hershey Medical Center, 500 University Dr., Hershey, PA 17033, USA;1. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States of America;2. Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America;3. Department of Medicine, University of Washington, Seattle, WA, United States of America;1. Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China;2. Department of Special Inspection, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou 510000, China;1. São Paulo State University, Botucatu, SP, Brazil;2. Pathology Institute of Araçatuba, Araçatuba, SP, Brazil;3. School of Medicine, Centro Universitário Católico Salesiano Auxilium (Unisalesiano), Araçatuba, SP, Brazil;1. Clinical Research Unit, Centre Henri Becquerel, Rouen 76038, France;2. Department of Clinical Haematology, Centre Henri Becquerel, Rouen 76038, France;3. Department of Pathology, Centre Henri Becquerel, Rouen 76038, France
Abstract:BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with myelofibrosis (MF). Bone marrow (BM) morphologic evaluation of myelofibrosis following allo-HSCT is known to be challenging in this context because resolution of morphologic changes is a gradual process.Patients and methodsWe compared BM samples of patients with myelofibrosis who underwent first allo-HSCT and achieved molecular remission by day 100 with BM samples of patients who continued to have persistent molecular evidence of disease following allo-HSCT.ResultsThe study group included 29 patients: 17 primary MF, 7 post-polycythemia vera (PV) MF, and 5 post-essential thrombocythemia (ET) MF. In this cohort there were 18 JAK2 p.V617F, 8 CALR; 1 MPL, and 2 patients had concurrent JAK2 p.V617F and MPL mutations. The control group included 5 patients with primary MF, one with post-PV MF, one with post-ET MF (5 JAK2 p.V617F; 2 CALR). Following allo-HSCT, both groups showed reduction in BM cellularity and number of megakaryocytes. The study cohort also less commonly had dense megakaryocyte clusters and endosteal located megakaryocytes and showed less fibrosis. There was no statistical difference in BM cellularity, presence of erythroid islands, degree of osteosclerosis, or megakaryocyte number, size, nuclear lobation, presence of clusters or intrasinusoidal location.ConclusionsFollowing allo-HSCT at 100 days, morphologic evaluation of BM in patients with MF cannot reliably predict persistence versus clearance of molecular evidence of MF. Disappearance of BM MF, dense megakaryocyte clusters, and endosteal localization of megakaryocytes are suggestive of disease response.
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