Optimizing Haploidentical Donor Selection for Pediatric Hematopoietic Cell Transplant

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.