Page 156 - 2020_11-Haematologica-web

M.M. Cuadrado et al.
lance continued in a subset of patients at risk of late re- activation (e.g., patients with GvHD, prior multiple re- activations). Twenty-three recipients shared a CMV seronegative status with the donor and did not have CMV reactivation. Of the remaining 39 patients, 35 (92%) had CMV re-activation before the CD34+-selected infusion. No patients had CMV re-activation following infusion. The relationship between complete or partial recovery and CMV serostatus correlated with CMV re-activation, with 23/35 (66%) of patients who had CMV re-activation showing a response versus 24/27 (89%) of those who did not have CMV re-activation (P=0.04). However, other variables related to the severity of CMV infection includ- ing earlier re-activation, higher peak CMV viremia, longer duration of antiviral drug treatment, higher number of CMV re-activations, active CMV infection at the time of infusion and CMV disease did not correlate with worse recovery (Online Supplementary Table S4).
Table 3. Multivariate analysis for recovery after CD34+- selected infusion.
Graft-versus-host disease
Acute GvHD following CD34+- selected infusion
occurred in a total of seven patients (11%) at a median of 15 days (range, 7-26 days; 3 patients had acute GvHD grade I-II and 4 patients had grade III-IV).
Chronic GvHD was seen in five patients (8%) who sur- vived for more than 100 days following CD34+-selected infusion (1 patient had mild, 1 had moderate and 3 had severe chronic GvHD). Of the six patients who received co-transfer of donor T cells, two developed acute GvHD grade III-IV and two developed mild and severe chronic GvHD.
Survival
At a median follow up of 6.4 years (range, 2.8-9.9), 29 patients (11/15 non-responding [73%], 7/8 with partial recovery [87%] and 11/39 with complete recovery [28%]) had died. The causes of death included infection (38%), relapse (34%), GvHD (16%), secondary malignancies (3%) and others (9%). The median overall survival for all patients was 5.4 years (95% confidence interval [95% CI]: 1.3-9.4). One and 5-year overall survival rates were 70% (95% CI: 58-82) and 54% (95% CI: 41-68), respectively. In
+
patients with complete recovery after CD34 -selected
infusion, the overall survival rates at 1 and 5 years were 86.7% (95% CI: 76-98) and 74.4% (95% CI: 59-89), respectively, while those in patients with partial recovery were 62.5% (95% CI: 28-97) and 16.7% (95% CI: 3-46) respectively. Patients showing no response had poor out- comes with overall survival rates of 33.3% (95% CI: 9-58) and 22.2% (95% CI: 5-47) at 1 and 5 years respectively (Figure 2A). Of the 15 patients who did not recover, three (20%) remain alive: one patient had red cell aplasia and is currently on periodic red cell transfusions with iron chela- tion; a second patient underwent second allogeneic SCT; and the third patient with trilineage poor graft function is requiring ongoing transfusional support and growth fac- tors. The remaining patients without response died, pri-
Active infection at the time of CD34+-selected infusion
Yes
No
Missing values 2
N OR (95% CI)
P-value
0.002
0.02
0.008
24 1.0
36 38.9 (3.9-388.3)
R/D CMV status Other
Negative/negative
37 1.0
23 16.8 (1.4-195.8)
Missing values 2
R/D sex
Unmatched
Matched
Missing values 2
R/D: recipient/donor; CMV: cytomegalovirus.
31 1.0
29 24.4 (2.3-254.5)
AB
Figure 2. Kaplan-Meier estimate of overall survival after CD34+-selected stem cell infusion. (A) Survival curves according to type of recovery; complete, partial or no recovery. (B) Survival curves in patients who recovered after CD34+-selected infusion, according to whether they had poor graft function in one or two lineages or poor graft function in all three lineages. CR: complete recovery; PR: partial recovery; NR: no recovery.
2644
haematologica | 2020; 105(11)