Donors other than matched siblings and low-intensity conditioning regimens are increasingly
used in haematopoietic stem cell transplantation. We aimed to compare the relative
risk of donor type and conditioning regimen intensity on the transplantation outcomes
of in patients with sickle cell disease.
For this retrospective cohort study, we collected data from 90 US centres reported
to the Center for International Blood and Marrow Transplant Research. Eligible patients
were younger than 50 years, had genetically confirmed sickle cell disease (Hb SS)
or sickle beta thalassemia (Hb Sβ), and underwent allogeneic haematopoietic cell transplantation
between Jan 15, 2008, and Dec 28, 2017. We considered transplants from donor-recipient
pairs matched at the allele-level (
HLA-A, HLA-B, HLA-C, and
HLA-DRB1), including HLA-matched sibling donors, haploidentical related donors, matched unrelated
donors, or mismatched unrelated donors. The main outcome was event-free survival.
The effect of donor type, conditioning regimen intensity (myeloablative, non-myeloablative,
and reduced-intensity regimens), age (≤12 or 13-49 years), sex, performance score,
comorbidity index, recipient cytomegalovirus serostatus, graft type (bone marrow,
peripheral blood, or umbilical cord blood), and transplantation period (2008–12 and
2013–17) on outcomes was studied using Cox regression models.
Of 996 patients with sickle cell disease and who underwent transplantation in 2008–17,
910 (91%) were included (558 [61%] patients had HLA-matched sibling donors, 137 [15%]
haploidentical related donors, 111 [12%] matched unrelated donors, and 104 [11%] mismatched
unrelated donors). The median follow-up was 36 months (IQR 18–60) after transplantation
from HLA-matched siblings, 25 months (12–48) after transplantation from haploidentical
related donors, 37 months (23–60) after transplantation from HLA-matched unrelated
donors, and 47 months (24–72) after transplantation from mismatched unrelated donors.
Event-free survival was worse in recipients aged 13 years or older than in those younger
than 13 years (hazard ratio 1·74, 95% CI 1·24–2·45; p=0·0014) and in those who received
a transplant from haploidentical related donors (5·30, 3·17–8·86; p<0·0001), matched
unrelated donors (3·71, 2·39–5·75; p<0·0001), and mismatched unrelated donors (4·34,
2·58–7·32; p<0·0001) than in patients who received a transplant from matched siblings.
There was no significant difference in event-free survival between recipients of transplants
from non-sibling donors: haploidentical related donors (1·43, 0·81–2·50; p=0·21) or
mismatched unrelated donors (1·17, 0·67–2·05; p=0·58) versus HLA-matched unrelated
donors, or mismatched unrelated donors versus haploidentical related donors (1·22,
0·65–2·27; p=0·98). Event-free survival was also worse in patients conditioned with
reduced-intensity regimens (1·97, 1·15–3·36; p=0·013) than in those conditioned with
non-myeloablative regimens, but did not differ between those who received myeloablative
compared with non-myeloablative regimens (1·57, 0·95–2·61; p=0·079). Interpretation
Our data suggest that event-free survival is improved in patients with sickle cell
disease who receive an allogenic transplantation at age 12 years or younger and those
with an HLA-matched sibling donor. For patients without a matched sibling available
for transplantation, our data do not favour one alternative donor type over another
in this setting.
National Institutes of Health and US Health Services Research Administration, Department
of Health and Human Services.