Unrelated Hematopoietic Stem Cell Donor Matching Probability and Search Algorithm

Table 3

Unrelated donor search algorithm for high, intermediate, and low probability categories aiming at the identification of 12/12, 10/10, or 9/10 matched donors. This algorithm is based on requesting blood sample from BMDW registries, and histocompatibility testing in the laboratory serving the transplant center(s). Alternatively HLA typing can be performed by the laboratory linked to each registry at the request of the transplant center. Intermediate resolution typing must resolve the main allele groups, for example, B*44:02 versus B*44:03 groups or C*07:01 versus 07:02 groups.

Probability	Steps	Procedure
High	1	Urgent transplant:
		(i) select 2–4 donors (incl. “back-up donor”) according to age, sex, CMV status, blood group
		(ii) type for HLA-A, B, C, DRB1/B3/B5, DQB1 at a high resolution level^(1)
	2	Nonurgent transplant: consider DPB1 matching (a 12/12 match is possible for >1/3 patients)
		(i) type for HLA-A, B, C, and DRB1, DQB1 at an intermediate resolution level
		(ii) type for DRB3 if DRB3 MM risk (i.e. DRB1*13:01 haplotypes)^(1)
		(iii) if DPB1 matched donor found: complete high resolution typing for all HLA loci
Interm	1	Select 4–6 potential donors and type for HLA-A, B, C, DRB1, and DQB1 at an intermediate level
		>1 potentially matched donor identified: select according non HLA criteria and complete high resolution typing
	2	no matched donor identified and urgent transplant: select according non HLA criteria and complete high resolution typing
	3	no matched donor identified and non-urgent transplant: request another set of 4–6 donors
Low	1	Consider a mismatch early in the search and request 4–6 donors:
		(i) type for HLA-A, B, C, DRB1/B3/B5, DQB1 at an intermediate resolution level
	2	No matched donor identified and urgent transplant:
		(i) select a donor among potential donors with single MM and complete high resolution typing
	3	No matched donor identified and nonurgent transplant:
		(i) request another 4–6 donors and type for HLA-A, B, C, DRB1/B3/B5, and DQB1 at an intermediate resolution level
	4	If no potential donors available in BMDW:
		(i) select donor(s) with a mismatch located at the locus where the patient’s rare allele is found
		(ii) if B MM: select donors with B MM associated with same HLA-C (e.g., B35:08 versus B*53:01 or B*13:01 versus B*57:01)
		(iii) if DRB1 MM : select donors with DRB1 mismatches associated with same DQB1 allele (e.g., DRB1*11:03 versus DRB1*12:01)
	5	If no mismatch accepted consider another HSC source (cord blood, haplo-identical donor) or a nontransplant protocol

⁽¹⁾HLA-A, B, C, DRB1, and DQB1 testing is performed by PCR-SSO on microbeads arrays (luminex technology, OneLambda HD reagents) by PCR-SSP (Genovision), and by mono-allelic PCR-SBT (Protrans). HLA-DRB3, DRB5, and DPB1 typing is performed by PCR-SSP.
MM : mismatches.