High concordance in grading reticulin fibrosis and cellularity in patients with myeloproliferative neoplasms.
The myeloproliferative neoplasms primary myelofibrosis, polycythemia vera, and, rarely, essential thrombocythemia are characterized by variable degrees of bone marrow fibrosis, either at presentation or upon progression. The increasing use of emerging therapies that may alter disease biology and morphology demands accurate and reproducible assessment of fibrosis grade. To assess concordance of hematopoietic cellularity and fibrosis grading, three hematopathologists independently evaluated a total of 728 bone marrow biopsies from 261 patients with myeloproliferative neoplasms on three clinical trials using fedratinib (SAR302503), a JAK2 inhibitor, including 249 taken at baseline and 479 on therapy. Concordance between the pathologists was evaluated by Pearson correlation coefficient (cellularity) and unweighted kappa statistic (fibrosis grade). There was high correlation of cellularity assessment (r=0.92) and fibrosis grading (kappa=0.83) between the three pathologists. Concordance with World Health Organization (WHO) grade 3 samples was higher compared with grades 0, 1, and 2. Concordance of fibrosis grading in pretreatment samples was superior to that of post-treatment samples (kappa=0.83 and 0.79, respectively, P=0.023). Our analysis suggests that the updated 2008 WHO reticulin fibrosis grading system is highly reproducible, even in patients undergoing JAK2 inhibitor therapy. This system is practically applicable to establish baseline fibrosis grade as well as changes in fibrosis in subsequent samples on therapy.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Olga
O
Pozdnyakova
Sanofi Oncology, Cambridge, MA, USA.
Kaida
K
Wu
Sanofi Oncology, Cambridge, MA, USA.
Abhay
A
Patki
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Scott J
SJ
Rodig
University of Cologne, Cologne, Germany.
Juergen
J
Thiele
Department of Pathology, WRN244, Massachusetts General Hospital, Boston, MA, USA.
Robert P
RP
Hasserjian
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D001856:Bone Marrow Examination; D005355:Fibrosis; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D060787:Neoplasm Grading; D015588:Observer Variation; D011087:Polycythemia Vera / Q000473:pathology; D011237:Predictive Value of Tests; D055728:Primary Myelofibrosis / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D015203:Reproducibility of Results; D012155:Reticulin / Q000378:metabolism*; D013449:Sulfonamides / Q000627:therapeutic use; D013920:Thrombocythemia, Essential / Q000473:pathology; D016896:Treatment Outcome; D000096926:Benzenesulfonamides
D000970:Antineoplastic Agents; D053614:Janus Kinase 2; D047428:Protein Kinase Inhibitors; D011759:Pyrrolidines; D012155:Reticulin; D013449:Sulfonamides; C528327:fedratinib; D000096926:Benzenesulfonamides; C507924:JAK2 protein, human