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R. Ram et al.
acute GvHD. In multivariate analysis, only use of ATG had a statistically significant impact on the incidence of acute GvHD (HR 0.327, 95%CI: 0.13-0.82; P=0.02).
Median time for the development of chronic GvHD was 9.4 (range, 2.5-12.4) months. At two years post HCT, the cumulative incidence of overall and moderate-severe chronic GvHD were 61% (95%CI: 47-72%) and 42% (95%CI: 34-51%), respectively (Figure 1B). In univariate analysis, ATG administration was associated with lower incidence of overall chronic GvHD, while prior acute GvHD was associated with an increased incidence of chronic GvHD (Table 2). Following multivariate analysis, only prior acute GvHD was associated with a statistically significant impact on chronic GvHD (HR: 1.96, 95%CI: 1.12-3.42; P=0.04).
Non-relapse mortality
Ten patients died because of non-relapse mortality. In six patients, death was preceded either by acute or chronic GvHD. There were three deaths within 30 days from HCT: one patient developed grade 3 acute GvHD, one patient who underwent HCT due to transformed chronic myelomonocytic leukemia (CMML) into AML with pre- transplant hepato-splenomegaly developed severe SOS, and one patient developed sepsis. The cumulative inci- dences of NRM at 30 days, three months, one year, and three years were 6%, 6% and 13%, and 16%, respectively (Figure 2A). There were three cases of late (>3 years after transplant) mortality: two patients had prior severe chron- ic GvHD, while the third, a 73-year old patient, died at the age of 78 with no transplant-associated toxicities. There was no difference between the three protocols in terms of NRM. Because of the low number of events, we did not perform regression analyses for NRM.
Disease response and relapse incidence
Response analysis performed on day 30 showed that only one patient (2% of the 48 patients who survived the
Table 1. Patients' characteristcs.
Domain
Sex, n male (%)
Age, median, range (years) Median days to HCT, range
Cytogenetics
Normal karyotype Complex karyotype Other
Molecular FLT3-ITD
JAK2 BCRABL FLT3-TKD MLL RUNX1
Prior Chemotherapy TAD/HAM
sHAM
7+3 only
7+3 plus salvage Azacitidine only
% blasts in marrow prior to HCT (range)
Preparative regimen FLAMSA-TBI-based FLAMSA-Treo-based FITCy-TBI-based
ATG
Donor
Matched-related Mismatched-related Matched-unrelated Mismatched-unrelated Female-to-male
CMV status (D/R) +/+
+/- -/+ -/-
Graft characteristics
Peripheral blood (%)
CD34, median, range (x106/kg) CD3, median, range (x108/kg)
All Cohort (n=51)
22 (43%)
54, 18-73 84 (25-183)
28 (55%) 13 (26%) 10 (19%)
14 (28%) 2 (4%) 1 (2%) 6 (12%) 1 (2%) 3 (6%)
7 (14%) 23 (45%) 11 (22%) 8 (13%) 3 (6%)
24 (5-93) %
13 (26%) 17 (33%) 21 (41%) 30 (59%)
19 (37%) 1 (2%) 26 (51%) 5 (10%) 12 (24%)
28 (54%) 5 (10%) 8 (16%) 10 (20%)
50 (98%) 6 (2.6-14.6) 1.9 (1-4.9)
A
Acute GvHD
B
Chronic GvHD
N: number; HCT: hematopoietic cell transplantation; TBI: total body irradiation; D/R: donor/recipient; ATG: anti-thymocyte globulin; CMV: cytomegalovirus.
Figure 1. Incidence of graft-versus-host disease (gvHD). (A) Grade 2-4 and grade 3-4 acute GvHD. (B) Overall and moderate-severe chronic GvHD. HCT: hematopoietic cell transplantation.
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