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Myeloablative MSD-SCT for SCA: long-term outcome
Table 1. Characteristics of sickle cell anemia patients transplanted in France with matched-sibling donors and myeloablative conditioning regi- men.
Period
PATIENTS’ CHARACTERISTICS Number
Phenotype, n
Sex (F/M)
Median age (range) years Age > 15 years, n (%)
Transfusion number: median (range) Ferritin: median (range) ng/ml
Pre-transplant SCA-complications
Nov 1988-Dec 2004 Blood Paper 2007
83
81 SS, 2 Sb0 37/46
8.8 (2.2-22) 9 (10.8%) 15 (2-119) 462 (13-3820)
Jan 2005- Dec 2012 New cohort
151
147 SS, 2 Sb0, 2 SDPunjab 73/78
8.1y (3-28.9)
23 (15.2%)
16.5 (2-108)
970 (8-6208)
Nov 1988-Dec 2012 Overall cohort
234
228 SS, 4 Sb0, 2 SDPunjab 109/125
8.4y (2.2-28.9)
32 (13.7%)
16 (2-61)
804 (8-6208)
Stroke+TIA,n(%) 30+3(39.8%) 20+3(15.2%) 50+6(23.9%)
Ischemic lesions, n (%) Silent infarcts , n (%) Stenoses, n (%)
Moya, n (%)
History of abnormal TCD, n (%) Abnormal TCD at transplant, n (%) ≥3VOCperyear,n(%) ≥2ACS,n(%)
Multiple osteonecroses, n (%)
Red cell alloimmunization (≥ 2), n (%) Rare erythroid group, n (%)
TRJV >= 2.7m/s, n (%)
Severe anemia, n (%)
Priapism, n (%)
Splenectomized total/partial, n (%)
Seizures, n (%)
48 (57.8%) 16 (19.3%) 30 (36.1%) 9 (10.8%) 8 (9.6%) 10 (12.0%) 28 (33.7%) 13 (15.7%) 13 (15.7%) 2 (2.4%)
3 (3.6%) 0 (0%) 10 (12.0%)
4 (4.8%)/0
7 (8.4%)
57 (37.7%) 34 (22.5%) 44 (29.1%) 7 (4.6%) 57 (37.7%) 8 (5.3%) 46 (30.5%) 36 (23.8%) 5 (3.3%)
5 (3.3%)
3 (2.0%)
5 (3.3%)
7 (4.6%)
5 (3.3%)
12 (7.6%%)/ 6 (4.0%)
4 (2.6%)
105 (44.9%) 50 (21.4%) 74 (31.6%) 16 (6.8%) 65 (27.8%) 18 (7.7%) 74 (31.6%) 49 (20.9%) 18 (7.7%)
7 (3.0%)
6 (2.6%)
5 (2.1%)
17 (7.3%)
5 (2.1%)
16 (6.8%) /6 (2.6%)
11 (4.7%)
Cytomegalovirus status in recipient at transplant was available in 219 of these patients and was positive in 167 (76%). Exclusion criteria were not defined in the protocol, but patients were always discussed in multidisciplinary meetings, and the final decision was left to the physician in charge of the patient. Patients with severe sequelae post-stroke were excluded,but several patients,for example those with hemiparesis,were transplanted.The main issue was to evaluate if the child could withstand the 4-6 weeks hospital- ization in the transplant unit.
years). All survivors had at least five years of follow up and results are presented in Table 2.
Engraftment
Two non-engraftments were observed, with rapid autologous reconstitution, in two patients transplanted with cord blood (CB) (Table 3). The first one, a patient who was transplanted 20 years ago, has not experienced any further SCA-related crisis since transplant, but still has 21% fetal Hb (HbF) (vs. <2% before SCT) and was still anemic (Hb 7 g/dL) at last visit. The second one, trans- planted 12 years ago, is currently on HU therapy because of recurrent crises. For the other 232 patients, the time to absolute neutrophil count >0.5x109/L was significantly shorter after bone marrow transplantation (BMT) com- pared to CB transplantation (CBT) [mean±Standard Deviation (SD); 20.7±5.7 vs. 32.0±10.0, respectively; P<0.001]. Similarly, platelets reached 50x109/L sooner after BMT (day 26.5±12.2) than after CBT (day 44.6±18.3; P=0.001).
Rejection
Rejection was defined as donor chimerism <5%. Despite initial successful donor engraftment, six rejections
were observed 0.5, 0.9, 1.2, 2.0, 2.3 and 9-years post trans- plant in patients transplanted before year 2005, as previ- ously reported.22 Five of them did not receive ATG as part of the preparative CR, and only one rejection occurred despite CR including ATG. Taking into account the two patients with non-engraftment and the six patients with rejection, the cumulative incidence of rejection for the overall cohort was 3.1% (95%CI: 0.7-5.5%) at five years; this was 20.0% (95%CI: 3.0-37.0%) in patients not pre- pared with ATG versus only 1.4% (95%CI: 0.0-3.0%) in those who received ATG (P<0.001). However, the ATG dose had no impact on the rejection risk (Figure 2A).
Transplant-related mortality
Seven deaths occurred after MSD-SCT. Five occurred in patients transplanted before year 2005, as previously reported.22 Two deaths occurred at 0.5 and 2.5 years post transplant in the second cohort, because of adenoviral encephalitis30 and GvHD-related obliterans bronchiolitis, respectively. The cumulative incidence of TRM at five years was 3.0% (95%CI: 0.8-5.2%) and significantly decreased with time from 6.0% (95%CI: 0.8-11.2%) before January 2005 to only 1.4% (95%CI: 0-3.4%) for the 151 patients transplanted since January 2005 (P=0.045).
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