Page 106 - 2019_09-HaematologicaMondo-web

M. Robin et al.
Table 1. Patients’ and transplant characteristics.
Whole cohort 2-year landmark N%N%
Total number of patients 2459 1055
Disease at time of transplant
Primary myelofibrosis 1904 78 Secondary myelofibrosis 421 17 Transformation into acute leukemia 134 5
837 79 188 18 30 3
Median age at HSCT, years 55 53.5
<45years 355 14 45-54years 729 30 55-64 years 1137 46 ≥65years 238 10
193 19 351 33 426 40 85 8
Interval primary diagnosis and transplant, median 26.7
308 29
747 71
645 63 378 37 191 18 855 82
150 14
905 86
471 45
565 55
<12months 743 30
≥12months 1716 70
Conditioning regimen
Reduced intensity 1502 63 Standard 877 37 Total body irradiation, Yes 423 17 No 2015 83
Source of stem cells
Marrow 332 14 Blood 2127 86
Donor type
HLA matched sibling donor 1022 43 Other 1379 57
N: number; HSCT: hematopoietic stem cell transplantation. Unreported data found for regimen and type of donor but always < 4%.
Outcome and predictors for outcome
In the entire cohort (2459 patients, without LM), OS and DFS at ten years were 41% (95%CI: 39-44) and 32% (95%CI: 30-35). Median follow up in the LM population was 49.7 months (95%CI: 47-52). In the 1,055 long-term survivors, 166 deaths were registered within ten years after HSCT. For all time periods, the most common cause of death was relapse of MF, followed by GvHD and infec- tion, with a higher occurrence of infection-related deaths between 2- and 5-years post-transplant (Table 2). In the LM population, secondary cancers occurred in 34 patients before the landmark and in 87 patients after the land- mark. This translated into a cumulative incidence in the LM population without cancer before the LM at ten years of 14% (11-18) ten years after the transplantation. The most frequent cancer was solid tumor (70%, of whom 3 breast cancers), followed by acute leukemia or myelodys- plastic syndrome (17%) and lymphoma (9%).
Grade 2-4 acute GvHD had occurred in 23% of the LM patients (n=245). Before LM, 56% (576 patients) of the patients in the LM population had chronic GvHD of whom 263 patients had an extensive chronic GvHD. Among patients without chronic GvHD before the 2-year LM, cumulative incidence of chronic extensive and limit- ed GvHD were 13% (8-18) and 9% (5-12%), respectively. Ten-year OS and DFS for 2-year survivors were 74% (71- 78%) and 64% (60-68%), respectively (Figure 1). In these patients, relapse incidence and non-relapse mortality ten years after transplant were estimated at 21% (17-24%) and 15% (12-18%) (Figure 1). Risk factors for mortality, DFS and relapse are shown in Table 3. Older age (P<0.001), type of myelofibrosis (higher risk for second- ary myelofibrosis, P=0.01), male sex (P=0.004) and no
Table 2. Causes of mortality after two years.
Years from transplant
Relapse/progression
Secondary malignancy* GvHD
Infection
Organ damage/toxicity Unknown
Total
2-5 y N%N%
>5-10 y
33 41
9 11 18 22 17 21 4 5 28
109
30 61
8 16 9 19 2 4
8
57
y: years; N: number; GvHD: graft-versus-host disease. *Including post-transplant lym- phoproliferative disease.
GvHD before LM (P=0.02) were associated with a signif- icantly higher risk of mortality. Older age (P=0.033), reduced intensity conditioning (RIC) (P=0.017), male sex (P=0.003), donor other than an HLA-matched related donor (P=0.01) and no GvHD before landmark were asso- ciated significantly with lower DFS. Use of a donor other than HLA-matched related donor (P=0.008), RIC (P=0.042) and no GvHD occurrence before the landmark (P<0.001) significantly increased the risk of relapse.
Comparison to general population
The excess mortality of the two-year landmark MF cohort was 21% (18-25%) at ten years; its population mortality was 4% (4-4.2%) (Figure 2). Excess mortality was lower in younger patients and in female gender recipients but remained considerably greater than the
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haematologica | 2019; 104(9)