Improved donor chimerism in relapse myelofibrosis post allogenic stem cell transplant with azacitidine and oral decitabine—First case report

Abstract

To date, allogenic stem cell transplant (ASCT) remains the only potential curative option for patients with primary myelofibrosis (PMF). However, relapse rates and associated mortality remain a concern. A second ASCT may not be feasible due to advancing age, declined functional status, donor unavailability, toxicities associated with a second ASCT. Herein, we report the first case of utilizing initially azacitidine and subsequently oral decitabine + cedazuridine (decitabine), in the context of relapsed PMF post-ASCT. Utilizing both hypomethylating agents provided disease control and improved donor/myeloid lineage chimerism levels, and the patient also remained transfusion independent, with preserved functional status and quality of life. K E Y W O R D S allogenic stem cell transplant, hypomethylating agent, myeloid lineage chimerism, primary myelofibrosis Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) driven by clonal disorders of hematopoietic progenitor cells with a risk of transformation to acute myeloid leukemia (AML) [1]. Despite advances in allogenic stem cell transplant (ASCT), relapse following ASCT for MF remains concerning [1, 2]. The type of donor such as a haploidentical-donor can have an impact on outcomes such as nonrelapse mortality and graft failure [3, 4]. However, once disease relapse (DR) occurs post-ASCT, treatment options are limited to donor lymphocyte infusion (DLI) and second ASCT; and overall survival (OS) is poor [1-4].Studies have demonstrated an association between decrease donor chimerism (DC)/myeloid lineage chimerism (MLC) and relapse [3,[5][6][7].Studies also show hypomethylating agents (HAs), that is, azacitidine and decitabine, are effective as salvage therapy (ST) in the setting of post-ASCT relapse by inducing immune response and improving MLC levels [8][9][10][11][12][13][14][15].