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P.A. Carpenter et al.
Table 2. Chronic graft-versus-host disease characteristics.
continued from the previous column
Two drugsa Three drugs N=72(%) N=66(%)
Two drugsa Three drugs N=72(%) N=66(%)
Time from transplant to enrollment in months, median (range)
Time from diagnosis of chronic GvHD to
enrollment in days, median (range)
Chronic GvHD risk statusa High
Standard
Category of chronic GvHD diagnosis relative to enrollment
Treatment naïveb
Early inadequate respondersc
Chronic GvHD presentation Overlap acute and chronic GvHD Classic chronic GvHD
Chronic GvHDs severityd Mild
Moderate
Severe
Chronic GvHD onset
De-novo
Quiescent Progressive
Skin score 0
1 2 3
Mouth score 0
1 2 3
Gastro-intestinal tract score 0
1 2 3
Eye score 0
1 2 3
Joints and fascia score 0
1 2 3
Genital tract score 0
1 2 3
Lung score 0
1 2 3
Liver score 0
1
7.3 (3.4, 28.6)
7.0 (0.0, 202.0)
37 (51.4) 35 (48.6)
49 (68)
23 (32)
36 (50.0) 36 (50.0)
16 (22.2) 45 (62.5) 11 (15.3)
30 (41.7) 10 (13.9) 32 (44.4)
14 (19.7) 16 (22.5) 22 (31.0) 19 (26.8)
20 (27.8) 31 (43.1) 18 (25.0) 3 (4.2)
40 (56.3) 17 (23.9) 12 (16.9) 2 (2.8)
33 (46.5) 25 (35.2) 9 (12.7) 4 (5.6)
53 (74.6) 10 (14.1) 7 (9.9) 1 (1.4)
43 (89.6) 3 (6.3) 2 (4.2) 0 (0.0)
62 (86.1) 8 (11.1) 1 (1.4) 1 (1.4)
19 (26.4) 14 (19.4)
7.7 (2.5, 42.4)
10.0 (0.0, 310.0)
32 (48.5) 34 (51.5)
36 (54.5)
30 (46.5)
34 (53.1) 30 (46.9)
13 (20.6) 45 (71.4) 5 (7.9)
24 (36.4) 14 (21.2) 28 (42.4)
19 (29.7) 11 (17.2) 20 (31.3) 14 (21.9)
16 (25.0) 26 (40.6) 17 (26.6) 5 (7.8)
33 (51.6) 21 (32.8) 8 (12.5) 2 (3.1)
29 (45.3) 24 (37.5) 10 (15.6) 1 (1.6)
49 (76.6) 11 (17.2) 4 (6.3) 0 (0.0)
28 (73.7) 8 (21.1) 0 (0.0) 2 (5.3)
54 (84.4) 6 (9.4) 3 (4.7) 1 (1.6)
21 (31.8) 23 (34.9)
2 3
Acute GvHD prior to enrollment Yes
No
22 (30.6) 17 (23.6)
42 (58.3)
30 (41.7)
14 (21.2) 8 (12.1)
42 (63.6)
24 (36.4)
continued in the next column
b
nisone ≥0.5 mg/kg/day (or equivalent) at the time of chronic GvHD diagnosis. Treatment-naïve:
newly diagnosed for <14 days. cEarly inadequate responders: previously treated and not responding ≤16 weeks from time of first diagnosis of chronic GvHD.dChronic GvHD severity was defined as per the NIH Consensus criteria.31
because of steroid use,23 and did not differ significantly at day 180 between patients in whom treatment had or had not been successful by day 180. Among patients in whom treatment was successful, the median baseline BAFF lev- els were slightly higher, 1.6 ng/mL (range, 0.2-17.7) versus 1.2 ng/mL (range, 0.1-19.4; P=0.046). BAFF/B-cell ratios were not significantly different between study arms or between patients in whom treatment was or was not suc- cessful.
Quality of life
Health-related quality of life was measured by self- report instruments, including the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT- BMT), Short Form-36 (SF-36). and Lee symptom scale. Figure 4 shows significantly better scores, at 2 and 6 months, with two drugs versus three drugs for the SF-36 Physical Component Summary, adjusted for baseline scores (P=0.02 and P=0.04), and demonstrated further by SF-36 Physical Functioning sub-scores (P=0.007 and P=0.001). Unadjusted, seven-item FACT-BMT Physical Well-Being scores were higher at 2 months with two drugs, but this observation did not hold when adjusted for baseline scores (P=0.27, graph not shown). Lee symptom scale scores did not differ between arms (data not shown).
Toxicity and adverse events
The proportion of patients with grade 3-5 toxicities was similar, 63.9% for those in the two-drug arm versus 56.1% in the three-drug arm. Thrombotic microangiopathy was observed in one patient (1.4%) in the two-drug arm and in three (4.5%) in the three-drug arm. The mean (standard deviation) increase in serum creatinine from baseline to 2 months was significantly higher with three drugs, 0.1 (0.3) mg/dL than with two drugs, 0 (0.2) mg/dL (P=0.002). The proportion of patients with serum creatinine >1.5 times baseline was significantly higher among patients treated with three drugs than among those treated with two drugs at both 2 months (11.7% versus 1.5%, P=0.025), and at 6 months (24.0% versus 7.8%, P=0.016). Twenty-seven subjects in the two-drug arm versus 27 in the three-drug arm (40.9% versus 37.5%, P=0.682) experienced severe to life-threatening/fatal infection episodes with slightly more infection episodes occurring in the three-drug arm (80 ver- sus 52). One patient in the two-drug arm and another three in the three-drug arm developed non-infectious pneumonitis.
Two drugs: prednisone/sirolimus; three drugs: prednisone/sirolimus/calcineurin-inhibitor; GvHD: graft-versus-host disease. aChronic GvHD risk status was defined as high-risk in patients with platelets <100,000,>50% skin involvement,bronchiolitis obliterans or those receiving pred-
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haematologica | 2018; 103(11)