Early Mixed Lymphoid Donor/Host Chimerism is Associated with Improved Transplant Outcome in Patients with Primary or Secondary Myelofibrosis

Abstract

We investigated risk factors for the development of mixed chimerism in 131 patients who underwent transplantation for myelofibrosis and determined the impact of lymphoid (CD3+) and myeloid (CD33+) chimerism on transplant outcome. Disease risk included DIPSS plus categories low to high. The median patient age was 58 years. Patients were conditioned with high-intensity (myeloablative) or low/reduced-intensity (nonmyeloablative) regimens and received a transplant from a related or unrelated donor. Mixed CD3⁺ chimerism was observed earlier after HCT, whereas CD33⁺ chimerism occurred later. Mixed chimerism was more frequent with low-intensity regimens than with high- intensity regimens. Mixed CD3⁺ chimerism did not lead to graft failure and was associated with a reduced incidence of acute GVHD and improved overall survival (OS) and relapse-free survival, whereas mixed CD33⁺ chimerism was associated with an increased incidence of relapse and reduced OS and relapse-free survival, independent of the CD34⁺ cell dose transplanted. Thus, mixed CD3⁺ chimerism in patients with myelofibrosis had a favorable impact on transplantation outcome and does not require therapeutic interventions.

Keywords: Conditioning intensity; GVHD; Mixed chimerism; Myelofibrosis; Relapse; Transplantation.