Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis

Abstract

Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events occur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged <45 years and 33% (13-53%) in patients aged ≥65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.

Figure 1.

Outcome of myelofibrosis patient from landmark time. (Left) Overall survival (OS; solid line) and disease-free survival (DFS: dashed line) from landmark time. (Right) Incidence of relapse (solid line) and non-relapse mortality (NRM) (dashed line). N: number; Tx: transplant.

Figure 2.

Mortality in myelofibrosis compared to the general population. (Top) Plots show mortality of the disease-free survivors (black line) and of the general population (gray line). (Middle) Plots show mortality of the myelofibrosis patients according to sex (black solid line: female; dashed line: male) and mortality in the general population (gray lines). (Bottom) Plots show mortality of disease-free survivors (black lines) and general population (gray lines) according to age categories. Tx: transplantation.

Figure 3.

Hazard rate for excess risk of mortality over time post transplant. Curves show hazard rates for two reference patients, based on the Cox model for the excess hazard. They were both 50 years (y) of age at time of hematopoietic stem cell transplantation (Tx), had primary myelofibrosis, received standard conditioning, did not receive total body irradiation, had a matched sibling donor, marrow was source of stem cells, and had no previous graft-versus-host disease. Solid line: male patient; dashed line: female patient.