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Predictors of recovery from poor graft function
Table 2A. Univariate analysis of pre-transplant variables as predictors of recovery after CD34+-selected infusion.
Table 2B. Univariate analysis of post-transplant variables as predictors of recovery after CD34+-selected infusion.
N
HCT-CI
Low risk 45 Intermediate risk 15 High risk 2
R/D sex
Unmatched 31 Matched 31
Donor type
Related donor 28 Matched unrelated donor 18 Mismatched unrelated donor 16
ABO status
No incompatibility 35 Major incompatibility 14 Minor incompatibility 13
CMV status (R/D)
Other 39 Negative/negative 23
EBMT Risk Score*
Early 19 Intermediate 28 Advanced 9 Non-malignant 6
Recovery, N (%)
P-value
P-value 20 12 (75%) 0.9
37 29 (78%) 11 11 (64%) 9 8 (89%)
3 3 (100%) 0.06
2 0
21 15 (71%)
41 32 (78%) 0.6
43 31 (72%)
19 16 (84%) 0.3
18 14 (78%)
23 18 (78%) 0.9
21 15 (71%)
20 17 (85%) 0.3
35 (78%)
11 (73%) 0.6
42 32 (76%)
Acute GvHD after allo-SCT Grades 0-I
Grades II-IV
Chronic GvHD after allo-SCT None
Mild Moderate Severe
Not evaluable*
Poor GF Primary
Secondary
Poor GF
3 lineages
1 or 2 lineages
Time from engraftment to secondary poor GF (median)
<130 days ≥130 days
Time from secondary poor GF to CD34+-infusion (median)
Time from allo-SCT to CD34+- infusion (median) <15 months 31 ≥15 months 31
CD34+- infusion dose (median)**
<3.18 31 ≥3.18 31
CD3+- infusion dose (median)***
<4.3 31 ≥4.3 31
Addition of T cells at the time of CD34+- infusion
No addition and full donor chimerism 22 Addition and mixed donor chimerism 6 No addition and mixed donor chimerism 25 Missing values 9
Recipient age at CD34+- infusion (median)
Age <50 years 31 Age ≥50 years 31
+
Donor age at CD34 -infusion (median)
N Recovery, N (%)
1 (50%)
19 (61%)
28 (90%)
0.008
22 (79%)
13 (72%)
12 (75%) 0.9
28 (80%)
10 (71%) 0.7
9 (69%)
26 (67%)
21 (91%) 0.03
15 (79%)
25 (89%) 0.02
4 (44%)
3 (50%)
<88 days
≥88 days
HCT-CI: Hematopoietic Cell Transplantation-specific Comorbidity Index; R/D: recipi- ent/donor; CMV: cytomegalovirus; EBMT: European Group for Blood and Marrow Transplantation. *EBMT Risk Score: early disease stage includes acute leukemia (AL) transplanted in first complete remission (CR),myelodysplastic syndrome (MDS) trans- planted untreated or in first CR; intermediate disease stage includes AL in second CR, chronic myeloid leukemia (CML) in all other stages than first chronic phase or blast crisis, MDS in second CR or in partial remission (PR), lymphoma and multiple myelo- ma in second CR, in PR or stable disease; late disease stage includes AL in all other dis- ease stages, CML in blast crisis, MDS in all other disease stages and lymphoma and multiple myeloma in all disease stages other than those defined as early or intermedi- ate. Stage is not applicable for aplastic anemia, primary immunodeficiencies and sick- le cell disease.
Finally, patients with early or intermediate stage disease had better recovery rates than patients with advanced dis- ease (15/19 [79%] and 25/28 [89%] versus 4/9 (44%), respectively; P=0.02). In multivariate analysis, only CMV serostatus, recipient-donor sex matching and infection remained statistically significant (Table 3). The type of poor graft function (primary or secondary), type of donor (related, matched or mismatched unrelated donor), ABO incompatibility, patient’s age, previous or active acute or chronic GvHD, CD34+ and CD3+ cell dose of the top-up infusion, CMV reactivation, full versus mixed donor chimerism and the interval from the initial allogeneic SCT to CD34+-selected infusion had no impact on the achieve- ment of complete or partial recovery (Table 2A, B). Chimerism status (available for 87% of patients in the 60 days prior to infusion) categorized into full donor or mixed chimerism also did not predict response. A subset of six patients with mixed chimerism received co-infusion of T cells at the time of CD34+-selected top-up. The co- transfer of donor T cells had no impact on recovery (5/6 [83%] who received co-infusion of T cells versus 16/22 [73%] who did not receive T cells showed complete or partial recovery; P=0.6).
Cytomegalovirus serostatus as a predictor of recovery
CMV monitoring by polymerase chain reaction was performed twice a week for the first 3 months and surveil-
Age <39 years 33
21 (68%)
26 (84%) 0.1
24 (77%)
23 (74%) 0.8
24 (77%)
23 (74%) 0.8
18 (82%)
5 (83%) 0.7
16 (73%)
22 (71%)
25 (81%) 0.4
22 (67%)
25 (86%) 0.07 12 (50%)
Age ≥39 years 29 +
Active infection at the time of CD34 - infusion Yes 24 No 36 Missing values 2
33 (92%)
GvHD (acute/chronic) at the time of CD34+- infusion
Yes 15
No 46 36(78%) 0.4 Missing values 1
<0.001
10 (67%)
Immunosuppression at the time of CD34+- infusion Yes 39 No 23
Chimerism before CD34+- infusion
Donor 21 Mixed 32 Missing values 9
29 (74%)
18 (78%) 0.7
17 (81%)
25 (78%) 0.8
GvHD: graft-versus-host disease; allo-SCT: allogeneic stem cell transplantation; GF: graft func- tion. *Patients died within 100 days after allo-SCT. **Cell dose x 106/kg recipient weight. ***Cell dose x 103/kg recipient weight.
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