Page 150 - 2019_06-Haematologica-web

M. Robin et al.
Results
Patients and transplant characteristics
The main patient, disease and transplant characteristics are described in Table 1. The median age of the partici- pants was 56.9 years [interquartile range (IQR), 50.6-61.5 years], the minimum was 22.1 years and the maximum was 75.5 years. There was a majority of male patients (68%). Patients who were not given ATG (n=152) and those who were (n=135) had similar characteristics regarding age, gender, and type of myelofibrosis (primary or secondary) but differed for other characteristics includ- ing splenectomy before transplant (38% versus 9%), DIPSS classification (intermediate-2 or high: 59% versus 68%), conditioning regimen (Table 1) and source of stem cells (bone marrow 17% versus 2%). More patients in the ATG group received calcineurin inhibitors alone (26% versus 7%). Concerning pre-transplant therapy, five patients in the non-ATG cohort and 14 in the ATG cohort received the JAK inhibitor ruxolitinib (Novartis Pharmaceuticals, Geneva, Switzerland). Regarding the brand of ATG used in the ATG group, 37 patients received Grafalon®, 96 received Thymoglobulin® and the brand was undeter- mined for two patients.
Engraftment
Six patients had primary graft rejection (3 in the ATG group and 3 in the non-ATG group). Four of these patients received a second HSCT and three of them were alive and in remission at the time of last reported follow-up. The cumulative incidences of neutrophil engraftment at day 60 were 96.3% [95% confidence interval (95% CI): 90.9%- 98.5%] and 94.1% (95% CI: 88.7%-96.9%) for the groups not given or given ATG, respectively (P=0.35). The corre- sponding cumulative incidences of platelet recovery at 6 months were 68.4% (95% CI: 60.3%-75.2%) and 80.3% (95% CI: 72.3%-86.1%) (P=0.09). Twenty-four patients (14 in the ATG group and 10 in the non-ATG group) had a secondary rejection at a median time of 9 months fol- lowing HSCT and all but one had disease progression. Half of them received a second HSCT, which failed to achieve a remission.
Outcomes
The median time to onset of acute GvHD was 36 days. The cumulative incidence of grade II-IV acute GvHD was significantly higher in the group of patients who did receive ATG than in the group of patients who did not: 41.4% (95% CI: 33.1%-49.5%) versus 26.2% (95% CI: 18.7%-34.3%) (P=0.0067) whereas the incidence of grade III-IV GvHD was similar in both groups (Figure 1). The median time to develop chronic GvHD was 198 days. The incidence of chronic GVHD was high (>50%) in both groups of patients (Figure 1) without there being signifi- cant differences according to whether or not ATG was administered. Rates of chronic extensive GvHD were also similar in the two groups. The cumulative incidence of relapse was 24.4% (95% CI: 16.5%-33.1%) after ATG and 18.6% (95% CI: 12.1%-26.1%) without ATG (P=0.083). The rate of non-relapse mortality was 32.5% (95% CI: 24.4%-40.7%) with ATG versus 31% (95% CI: 20.9%- 41.6%) without ATG. During the follow-up period, a total of 65 patients in the non-ATG group and 44 in the ATG group died. The primary cause of death was related to myelofibrosis progression in 34% non-ATG patients and
Table 1. Patient, disease and transplant characteristics. No ATG
P value 0.07
0.53
0.13
0.07
0.02
<0.0001
0.58
0.018
< 0.0001
<0.0001
0.90
0.11 <0.0001
<0.0001
0.38
0.27
Total number
Median age, years (IQR)
Recipient gender Male (%) Female (%)
Median time from diagnosis
to transplant in months (IQR)
Disease
Primary myelofibrosis (%) Secondary myelofibrosis (%) Transformation into AML (%)
Date of transplantation Before 2010
2010 and after
Splenectomy before transplant (%)
Lille score Low
Intermediate
High
DIPSS score Low
Intermediate-1 Intermediate-2 High
Missing
Conditioning regimen TBI-cyclophosphamide or fludarabine Busulfan-cyclophosphamide Fludarabine-busulfan±other Fludarabine-melphalan±other FLAMSA
Fludarabine-thiotepa
GvHD prophylaxis
Calcineurin inhibitor alone
Calcineurin inhibitor and methotrexate Calcineurin inhibitor and MMF
Other
Missing
152
56 (50-61)
100 (66) 52 (34)
41 (15-120)
97 (64) 44 (29) 11 (7)
52 (34)
100 (66) 42 (38)
30 (20) 78 (51) 44 (29)
21 (18) 27 (23) 45 (39) 23 (20) 36
30 (20) 18 (12) 37 (24) 62 (41) 3 (2)
2 (1)
8 (5) 63 (42) 75 (49) 4 (3) 1 (0.6)
95 (63) 57 (37) 0
115 (76) 39 (26)
26 (17)
126 (83)
37 (24) 63 (41) 21 (14) 31 (20)
90 [80-100]
142/147 (96%)
ATG
135
58 (51-62)
94 (70) 41 (30)
30 (9-84)
83 (61) 50 (37) 3 (2)
29 (21)
106 (79) 12 (9)
31 (23) 58 (43) 46 (34)
6 (6) 24 (25) 32 (34) 32 (34) 41
2 (1.5)
2 (1.5) 110 (81) 14 (10) 7 (5) 0
39 (29) 47 (35) 46 (34) 3 (2)
0
82 (61) 52 (39) 1
113 (84) 3 (2)
3 (2)
132 (98)
44 (32) 50 (37) 20 (15) 21 (16)
90 (80-100]
116/124 (93%)
Recipient CMV serostatus Positive
Negative
Missing
Conditioning regimen Reduced intensity TBI-based
Source of stem cells Marrow
Blood
Gender
Male recipient / female donor Male recipient / male donor Female recipient / female donor Female recipient / male donor
Karnosfsky score, median [range]
80% or more, n (%)
ATG: antilymphocyte globulin; IQR: interquartile range; AML: acute myeloid leukemia; DIPSS: Dynamic International Prognostic Scoring System; TBI: total body irradiation; FLAMSA: fludara- bine, cytarabine and amascrine reduced intensity conditioning; GvHD: graft-versus-host disease; MMF: mycophenolate mofetil; CMV: cytomegalovirus.
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haematologica | 2019; 104(6)