MPN-402: Delayed Resolution of Bone Marrow Morphological Changes of Myelofibrosis Following Successful Stem Cell Transplant and Molecular Clearance of Disease: A Cautionary Tale

Abstract

Context: Allogeneic stem cell transplant (allo-SCT) is a curative option for patients with myelofibrosis (MF). Reversal of the bone marrow (BM) morphologic features of MF often lags following allo-SCT and may create diagnostic challenges in disease surveillance. Objective: To determine which morphologic parameters could determine the disease persistence in patients with BM fibrosis following allo-SCT. Design: We compared the morphologic features typically associated with myelofibrosis in pre-transplant and post-transplant BM samples in a cohort of patients with BM fibrosis who achieved complete clearance of JAK2, MPL, and/or CALR mutations following allo-SCT. Setting: MDACC. Patients or other participants: Patients with primary or secondary MF and a driver mutation in a pre-transplant BM sample who achieved a molecular clearance after allo-SCT. Interventions: N/A. Main outcome measures: N/A. Results: Patients (n=27) included 12 men and 15 women with a median age of 63 years (range 42-76 years) diagnosed with primary myelofibrosis (n=17), post-essential thrombocythemia (post-ET) MF (n=5), and post-polycythemia vera (post-PV) MF (n=5). Driver mutations included JAK2 p.V617F (n=18), MPL (n=4), and CALR (n=7). Two patients with post-PV-MF had concurrent JAK2 and MPL mutations. Compared to pre-transplant samples, post-transplant samples demonstrated significantly fewer megakaryocytes (p Conclusion: Reversal of BM morphologic features following allo-SCT for MF lags behind molecular clearance. Re-appearance of erythroid islands, normalization of BM cellularity and disappearance of high-grade BM fibrosis and endosteal localization of megakaryocytes represent reassuring findings in evaluation of a response or recurrence.