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F. Bernaudin et al.
Table 2. Matched-sibling donor hematopoietic stem cell transplantation (MSD-SCT) procedure and outcome in sickle cell anemia patients trans- planted in France.
Period
Number of Patients
Conditioning regimen ATG dose
0 mg/kg, n (%)
5-15 mg/kg, n (%)
20 mg/kg, n (%)
not recorded, n (%) Stem cell source
Bone Marrow (BM), n (%) Cord Blood (CB), n (%) CB+BM, n (%)
PBC, n (%)
Outcome
Median Follow-up (range) Non-Engraftment, n (%) Rejection, n (%)
Deaths, n (%)
Nov 1988-Dec 2004 Blood Paper 2007
83
Busulfan/Cyclophosphamide Rabbit ATG
17 (20.5%)
18 (21.7%)
40 (48.2%)
8 (9.6%)
70 (84.3%) 11 (13.3%) 1 (1.2%) 1 (1.2%)
13.8 years (0.1-27.6)
1 (1.2%)
6 (7.2%)
5 (6.0%)
II (n=11), III (n=4), IV (n=2) mild (n=7), extensive (n=2)
7.5% (1.5-13.5%)
6.0% (0.8-11.2%) 86.9% (79.5-94.3%) 20.4% (11.6-29.2%) 11.2% (4.2-18.2%)
15 (18.1%)
6 (7.2%)
0 (0%)
18 (21.7%)
Jan 2005- Dec 2012 New cohort
151
3 (2.0%) 18 (11.9%) 124 (82.1%) 6 (4.0%)
125 (82.8%) 19 (12.6%) 7 (4.6%) 0 (0%)
6.8 years (0.4-13.2)
1 (0.7%)
0 (0%)
2 (1.3%)
II (n=24), III (n=5), IV (n=1) mild (n=11), extensive (n=4)
0.7% (0-2.1%)
1.4% (0-3.4%) 97.9% (95.5-100%) 20.0% (13.4-26.6%) 10.1% (5.1-15.1%)
1 (0.7%)
8 (5.3%)
2 (1.3%)
38 (25.2%)
Nov 1988-Dec 2012 Overall cohort
234
20 (8.5%) 36 (15.4%) 164 (70.1%) 14 (6.0%)
195 (83.3%) 30 (12.8%) 8 (3.4%) 1 (0.4%)
7.9 years (0.1-27.6)
2 (0.9%)
6 (2.6%)
7 (3.0%)
II (n=35), III (n=9), IV (n=3) mild (n=18), extensive (n=6)
3.1% (0.7-5.5%)
3.0% (0.8-5.2%) 93.9% (90.7-97.1%) 20.1% (14.9-25.3%) 10.5% (6.5-14.5%)
16 (6.8%)
14 (6.0%)
2 (0.9%)
56 (23.9%)
Acute GvHD, grade (n)
Chronic GvHD,
Cumulative Incidences (95%CI) Non-Engraftment/Rejection at 5 years Transplant Related Mortality at 5 years Event-Free Survival at 5 years
Acute GVHD ≥ II at Day 100 Chronic GVHD at 5 years
Other post-SCT complications Seizures, n (%)
Hemorrhagic cystitis, n (%) Veno-occlusive disease, n (%)
CMV replication
Cytomegalovirus (CMV) donor status,available in 217,was positive in 133 patients (61%).ABO compatibility was available in 212 donor-recipient couples,and major and minor incompatibility was present in 34 (16%) and 36 patients (17%), respectively. There was donor/recipient sex mismatch in 120 cases (FM: 61; MF 59).
All the boys who were pre-pubertal at transplant and of pubertal age at the last visit developed normal puberty with normal testosterone, FSH and LH levels, in keeping with their bone age and pubertal status. At last visit, 19 males were over 25 years of age. Three of them who had been transplanted 11, 12 and 20 years ago fathered spon- taneously. Pre-transplant sperm cryopreservation was per- formed in all pubertal males and pre-transplant testicular tissue cryopreservation has been systematically per- formed since year 2010 in prepubertal boys (n=25) (medi- an age: 7.5 years; range: 3.4-10.2). However, so far, no patient has requested testicular fragment autografting (median age at last visit: 13.7 years; range: 5.8-21.2).
Chimerism studies
Chimerism was assessable in 208 patients and was cat- egorized as full donor chimerism (>95% donor cells), rejection (<5% donor cells), and low (5-50% donor cells) or high (50-95% donor cells) mixed chimerism. At one year, full donor chimerism was present in 112 patients
(54%), while 92 patients (44%) had mixed chimerism (83 high, and 9 low), and 4 (2%) had <5% donor cells (the 2 patients with no-engraftment and 2 who rejected the graft at 0.5 and 0.9 years).
Multivariate logistic regression analysis showed that the ATG dose (OR=1.06 per 1 mg/kg increase, 95%CI:1.01- 1.12; P=0.017) and recipient’s age (OR=0.94 per year increase, 95%CI: 0.88-0.99; P=0.041) were independently inversely associated with the presence of mixed chimerism at one year. Moreover, cGvHD was signifi- cantly more frequent (P=0.018) in patients with full donor chimerism (18 of 112; 16.1%) than in those with mixed chimerism (5 of 92; 5.5%), These five patients all had donor cell% >75%. No significant association was found between ABO compatibility and chimerism.
Chimerism on separated populations (CD3+ and CD3–) was assessed in 103 patients. Whole blood donor cell chimerism was more significantly correlated with the CD3– (r=0.917, P<1x10-128) than with the CD3+ (r=0.418, P<1x10-15) population. During the first two years post
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