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M. Robin et al.
to Cox model (variables from Table 4) transplanted at the age of 50 years; the hazards are given for men and for women separately. We can see that there is a decline in hazard of excess mortality over time post HSCT, but after three years (5 years post-transplant), there is a plateau.
Discussion
This EBMT report of 1,055 patients alive and in remis- sion at two years after HSCT is the largest study of long- term post-transplant outcome in patients with MF. Results indicate that survival ten years after transplanta- tion in these 2-year survivors is 74%, but also that the
mortality rate does not decrease to that expected in the general population. This is the first long-term study in MF using LM analytical methods. It had previously been reported in other diseases that long-term outcome in transplanted patients remains lower than expected in the general population (except in aplastic anemia).20,21 Our results can be considered disappointing as compared to previous publications, especially from the Center for International Blood and Marrow Transplant Research,20 but the median age was two decades higher in our cohort, which could explain the higher long-term mortal- ity. Indeed, we could confirm that in a subgroup of patients aged under 45 years, OS was very good at 86% ten years after transplantation. Two additional recent long-term analyses in patients with chronic malignancies [chronic lymphocytic leukemia (CLL) and myelodysplas- tic syndrome (MDS)] from the EBMT registry included patients with a median age closer to MF patients estimat- ed, with long-term survival lower than in this MF cohort.27,24 Similar risk factors for mortality were found with a better OS in women and in younger24 patients. The reason for the higher risk in male recipients is not clear but it is usually thought to be due to behaviors which place the patient at higher risk, and also to a higher propensity towards comorbidities such as cardio-vascular disease.28 In contrast, an EBMT study of patients with acute myeloid leukemia did not show age or sex to be predictors for OS.29
Like in other malignant disorders, late relapse was the leading cause of death in MF patients following HSCT.19- 22,24,29 Incidence of relapse at ten years after transplant in the long-term survivors is 21%, in agreement with that expected in other malignant disorders. This highlights the fact that, even if the relapse risk decreases over time, it
Table 4. A multivariable Cox proportional hazards model for excess mortality in the period between two and ten years after hematopoietic stem cell transplantation for patients alive and disease-free at two years after hematopoietic stem cell transplantation.
Hazard ratio
Patient sex
Male 1
95% confidence interval
0.41 - 0.93
1.08 - 1.69
1.18 - 2.78
0.74 - 1.82 0.75 - 2.08
0.75 - 1.63
0.48 - 1.44
0.44 - 0.96
P
0.022
0.008
0.007
0.527 0.384
0.623
0.515
Female
0.62
1.81
Age (per decades)
1.35 Primary myelofibrosis 1
Disease
Secondary myelofibrosis
Conditioning regimen
Standard 1
Reduced intensity regimen NoTBI 1
TBI in regimen
1.25
1.16
Donor
Matched sibling donor 1
GvHD
No 1 Any 0.65
1.1 Marrow 1
0.83
Other donor
Source of stem cells Blood
TBI: total body irradiation; GvHD: graft-versus-host disease.
0.031
1786
haematologica | 2019; 104(9)
A
B
C
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 cat- egories. Tx: transplantation.