01.12.2019 | Research | Ausgabe 1/2019 Open Access

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients
- Zeitschrift:
- Journal of Hematology & Oncology > Ausgabe 1/2019
Publisher’s Note
Background
Patients and methods
Inclusion and exclusion criteria
Donors
Transplant procedures
Definitions and statistical analysis
Study design
End points
Statistical analyses
Characteristics
|
ATG-PTCy cohort (
n = 114)
|
ATG cohort (
n = 125)
|
P value
|
---|---|---|---|
Recipient age (year, median, range)
|
27 (5–52)
|
24 (4–65)
|
0.004
|
HLA-matching (A, B, DR)
|
0.001
|
||
3/6
|
94 (82%)
|
78 (62%)
|
|
4/6 or 5/6
|
20 (18%)
|
47 (38%)
|
|
Recipient gender
|
0.35
|
||
Male
|
63 (55%)
|
77 (62%)
|
|
Female
|
51 (45%)
|
48 (38%)
|
|
Disease type
|
0.99
|
||
Acute myeloid leukemia (AML)
|
55 (48%)
|
59 (47%)
|
|
Acute lymphoblastic leukemia (ALL)
|
47 (41%)
|
52 (42%)
|
|
Myelodysplastic syndromes (MDS)
|
9 (8%)
|
11 (9%)
|
|
Chronic myeloid leukemia (CML)
|
3 (3%)
|
3 (2%)
|
|
Disease risk index
|
0.20
|
||
Low/intermediate
|
101 (88%)
|
103 (83%)
|
|
High/very high
|
13 (12%)
|
22 (17%)
|
|
Minimal residual disease at transplant
|
0.86
|
||
Negative
|
93 (82%)
|
104 (83%)
|
|
Positive
|
21 (18%)
|
21 (17%)
|
|
Donor source
|
0.19
|
||
Mother
|
80 (70%)
|
98 (78%)
|
|
Collateral relatives
|
34 (30%)
|
27 (22%)
|
|
Donor gender male vs female
|
27 vs 7
|
20 vs 7
|
|
Donor age (year, median, range)
|
46 (12–67)
|
42 (10–61)
|
|
Maternal vs paternal line
|
20 vs 14
|
19 vs 8
|
|
Donor gender
|
0.15
|
||
Male
|
27 (24%)
|
20 (16%)
|
|
Female
|
87 (76%)
|
105 (84%)
|
|
Donor-recipient pair
|
0.20
|
||
Female to male
|
68 (60%)
|
64 (51%)
|
|
Others
|
46 (40%)
|
61 (49%)
|
|
Donor age (year, median, range)
|
46 (12–67)
|
42 (10–61)
|
0.002
|
Blood type matching
|
0.020
|
||
Match
|
51 (45%)
|
75 (60%)
|
|
Mismatch
|
63 (55%)
|
50 (40%)
|
|
Median mononuclear cell (range, 10
8/kg)
|
8.2 (3.3–11.8)
|
10.4 (3.8–26.1)
|
< 0.001
|
Median CD34
+ cells (range, 10
6/kg)
|
1.9 (0.5–14.1))
|
3.4 (1.6–21.2)
|
< 0.001
|
Median CD3
+ cells (range, 10
8/kg)
|
1.4 (0.3–5.7)
|
1.5 (0.3–11.1)
|
0.63
|
Year of transplant
|
0.006
|
||
April 2015 to August 2016
|
40 (35%)
|
66 (53%)
|
|
September 2016 to June 2018
|
74 (65%)
|
59 (47%)
|
|
Median follow-up (range, days)
|
587 (57–1399)
|
682 (3–1448)
|
0.20
|
Median follow-up in survivors (range, days)
|
661 (128–1399)
|
859 (230–1448)
|
0.007
|
Results
Study population
Low-dose PTCy significantly reduced acute and chronic GvHD
Outcome
|
Hazard ratio (95% CI)
|
P value
|
---|---|---|
ANC recovery
|
||
Cohort ATG-PTCy vs ATG
|
0.29 (0.21–0.41)
|
< 0.001
|
Other significant factors
|
||
Mononuclear cell count
|
1.09 (1.04–1.14)
|
< 0.001
|
CD34
+ cell count
|
1.08 (1.01–1.15)
|
0.012
|
Platelet recovery
|
||
Cohort ATG-PTCy vs ATG
|
0.30 (0.21–0.42)
|
< 0.001
|
Other significant factors
|
||
Mononuclear cell count
|
1.06 (1.01–1.11)
|
0.008
|
Acute GvHD ≥ grade 2
|
||
Cohort ATG-PTCy vs ATG
|
0.58 (0.35–0.96)
|
0.036
|
Acute GvHD ≥ grade 3
|
||
Cohort ATG-PTCy vs ATG
|
0.28 (0.11–0.69)
|
0.006
|
Total chronic GvHD
|
||
Cohort ATG-PTCy vs ATG
|
0.60 (0.38–0.99)
|
0.047
|
Non-relapse mortality
|
||
Cohort ATG-PTCy vs ATG
|
0.26 (0.08–0.75)
|
0.014
|
Disease risk index
|
||
Low/int vs high
|
0.28 (0.12–0.68)
|
0.005
|
Relapse
|
||
Cohort ATG-PTCy vs ATG
|
0.65 (0.28–1.50)
|
0.31
|
Disease-free survival
|
||
Cohort ATG-PTCy vs ATG
|
0.44 (0.22–0.86)
|
0.016
|
Disease risk index
|
||
Low/int vs high
|
0.51 (0.27–0.99)
|
0.048
|
Overall survival
|
||
Cohort ATG-PTCy vs ATG
|
0.47 (0.22–1.01)
|
0.055
|
Disease risk index
|
||
Low/int vs high
|
0.48 (0.23–0.99)
|
0.048
|
GVHD and relapse-free survival
|
||
Cohort ATG-PTCy vs ATG
|
0.59 (0.38–0.92)
|
0.021
|
Hematopoietic recovery, infection, and transplant outcomes
Cause of death
|
ATG-PTCy cohort (
n = 16)
|
ATG cohort (
n = 27)
|
---|---|---|
Relapse
|
9 (56%)
|
8 (30%)
|
GVHD
|
0
|
7(26%)
|
Infection other than CMV/EBV
|
5 (31%)
|
10 (37%)
|
CMV disease
|
1 (6%)
|
0
|
Organ failure
|
1 (6%)
|
2 (7%)
|