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Severity of chronic GvHD after alternative donor HCT
(Figure 1B). The median follow-up times after the onset of chronic GvHD were 48 (range, 4-121) months for UCB, 60 (range, <1-123) for Haplo/PTCY, and 46 (range, 4-131) for 1-mMUD HCT. The median time from HCT to diagnosis of chronic GvHD was shorter in the UCB recipients than in 1-mMUD HCT recipients [3.9 (range, 2.6-18.2) versus 7.8 (range, 2.7-38.2) months, P=0.001]. As shown in Table 2, the incidence frequencies of overlap chronic GvHD
Table 1. Characteristics of the study population according to alternative donor group.
(>80%) and of prior acute GvHD (>70%) were high in all three groups. These findings are consistent with the fre- quent diagnosis of upper gastrointestinal GvHD at our center.8 The severity of chronic GvHD at diagnosis was significantly lower in the UCB group than in the 1-mMUD group (P=0.008) (Table 2), but the severity of GvHD man- ifestations at the onset of chronic GvHD did not differ between the Haplo/PTCY and the 1-mMUD groups (P=0.74) (Table 2). According to the National Institutes of Health Global Severity scale, the incidence of moderate or severe chronic GvHD at diagnosis was 62% in the UCB group, 76% in the Haplo/PTCY group and 83% in the 1- mMUD group. Table 2 displays additional characteristics of the chronic GvHD according to the alternative donor HCT groups.
Sites of chronic GvHD and the presence of eosinophilia at any time during the course of chronic GvHD among the three alternative donor HCT groups are displayed in Figure 2. Mouth and skin were the most common sites of chronic GvHD in the three groups (>80%). Eyes were affected by chronic GvHD of any degree at any time in 75% of the 1-mMUD, 52% of the Haplo/PTCY, and 34% of the UCB HCT recipients. The same pattern was identi- fied for hepatic involvement at any time (56% of 1-
A
B
Figure 1. The cumulative incidence of chronic graft-versus-host disease is high- er in the mismatched unrelated donor group than in the cord blood or HLA-hap- loidentical groups, but survival does not differ between the groups. Cumulative incidence of (A) chronic graft-versus-host disease and (B) progression-free sur- vival after transplant according to alternative donor hematopoietic cell trans- plant group. NIH: National Institutes of Health; cGVHD: chronic graft-versus-host disease; URD Mism: mismatched unrelated donor; Cord: umbilical cord blood; Haplo: haplorelated bone marrow or peripheral blood; PFS: progression-free sur- vival.
Characteristic
Age at transplant (years), median (range)
Female, n. (%)
Race, n. (%)* White Other
Recipient CMV seropositive,
n. (%)**
Diagnosis, n. (%)
Acute myeloid leukemia Myelodysplastic syndrome Acute lymphocytic leukemia Chronic lymphocytic leukemia Chronic myeloid leukemia Hodgkin lymphoma Non-Hodgkin lymphoma1 Multiple myeloma2
Others3
Conditioning regimen, n. (%)4 Non-myeloablative/reduced intensity Myeloablative
GvHD prophylaxis, n. (%)
CNI and MMF
CNI and MTX
Cy posttransplant plus CNI and MMF Other
Graft source, n. (%) Peripheral blood Bone marrow Umbilical cord blood
Double units infused HLA-match, n. (%)
7/8
4-6/8
5-6/6 0 35 (21) 0
Alternative donor group Unrelated Umbilical Related
mismatched cord blood haploidentical (N=145) (N=163) (N=88)
55 (22-77)
54 (37)
113 (82) 24 (18)
90 (62)
53 (37) 31 (28) 17 (12) 9 (6) 11 (8) 1 (1) 12 (8) 8 (6)
3 (2)
69 (48)
76 (52)
145 (100) -
-
-
42 (18-73)
83 (51)
85 (56) 68 (44)
103 (64)
82 (50) 23 (14) 37 (23) 2 (1)
7 (4) 0
7 (4) 0
5 (3)
43 (26)
120 (74)
163 (100)
0
0
3(2) 0 1(1)
48 (18-75)
35 (40)
59 (69) 26 (31)
52 (59)
21 (24) 6 (7) 5 (6) 3 (3) 2 (2) 25 (28) 21 (24) 4 (5) 1 (1)
71 (81)
17 (19)
71 (49) 71 (49) 0
0
31 (35) 57 (65) -
-
0
87 (99)
-
-
163 (100) 157 (96)
4/6 3/6
Follow-up after HCT (months),
Median, (range)
0
0 92(56) 1(1)
0 36(22) 80 (91)
46 (4-131) 48 (4-121) 60 (<1-123)
145 (100)
0 0 6(7)
1 (1)
**Unknown for 21 patients. **Unknown for three patients. 1Includes four cases of prolympho- cytic leukemia. 2Includes two cases with plasma cell leukemia. 3Includes mycosis fungoides (n=2), polycythemia vera (n=2), and one each of the following diagnoses: immune deficiency disorder, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic sclerosis and unspec- ified neoplasm. 4Myeloablative conditioning regimens contained total body irradiation ≥5 Gy single dose or ≥8 Gy fractioned or busulfan >8 mg/kg orally or intravenous equivalent.Non-mye- loablative or reduced intensity conditioning consisted of fludarabine + total body irradiation (200-400 cGy) ± cyclophosphamide. CMV: cytomegalovirus; GvHD: graft-versus-host disease; CNI: calcineurin inhibitor; MMF: mycophenolate mofetil; MTX: methotrexate; Cy: cyclophos- phamide.
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