小児造血細胞移植における半数一致ドナー選択の最適化

Critical guidance on selecting haploidentical donors for pediatric patients is lacking. It is unclear whether parents, siblings, and extended family affect acute and chronic graft-versus-host disease (aGVHD and cGVHD) differently.

We analyzed 1,069 pediatric (<19 years) recipients of hematopoietic cell transplant during 2013-2019. Primary end points were aGVHD frequency at 100 days and cumulative incidence of cGVHD at 2 years, assessed by donor age (<18 years, 18-35, >35 years) and donor relationship, with multivariable analysis.

Donor age: Increased grade II-IV aGVHD occurred with older donors: >35 years (31%, odds ratio [OR], 1.7 [95% CI, 1.0 to 2.8]; P = .05) and 18-35 years (23%, OR, 2.5 [95% CI, 1.5 to 4.2]; P = .0003), versus < 18 years (15%, reference OR, 1). Increased cGVHD occurred in older donors: >35 years (incidence 30% [95% CI, 28 to 32]; hazard ratio [HR], 2.2 [95% CI, 1.3 to 3.9]; P = .004) and 18-35 years (incidence 26% [95% CI, 23 to 29]; HR, 2.1 [95% CI, 1.3 to 3.5]; P = .0028) compared with <18 years (incidence 16% [95% CI, 12 to 20]; reference HR, 1). Donor relationship: Patients with parental donors had higher aGVHD risk than siblings (mother: OR, 1.9 [95% CI, 1.3 to 2.8]; P = .001; father: OR, 1.7 [95% CI, 1.1 to 2.5]; P = .009). Patients with maternal donors had a significantly higher risk of cGVHD than paternal (HR, 2.3 [95% CI, 1.6 to 3.3]; P < .0001) and sibling donors (HR, 2.3 [95% CI, 1.7 to 3.4]; P < .0001). Age-relationship interaction: Maternal donors were associated with more GVHD than siblings, regardless of age (aGVHD II-IV, mothers >35 years, HR, 2.53 [95% CI, 1.46 to 4.41]; mothers 18-35 years, HR, 2.05 [95% CI, 1.14 to 3.69]) (cGVHD: mothers >35 years, HR, 3.10 [95% CI, 1.72 to 5.60]; mothers 18-35 years, HR, 3.35 [95% CI, 1.8 to 6.25]).

Donors <18 years are associated with reduced aGVHD and cGVHD, whereas maternal donors are associated with increased cGVHD risk. For pediatric patients, sibling donors should be considered to reduce GVHD.