How do you find a match for a bone marrow transplant?

Finding a Match for Bone Marrow Transplant

The search for a bone marrow transplant donor begins with high-resolution HLA typing of the patient at HLA-A, -B, -C, and -DRB1 loci, followed by a hierarchical search starting with siblings (25% match probability), then proceeding to unrelated adult donors through registries like the National Marrow Donor Program, and finally considering cord blood units or haploidentical donors if no 8/8 matched donor is identified. 1, 2

Step 1: HLA Typing of the Patient

• Obtain high-resolution HLA typing for HLA-A, -B, -C, and -DRB1 as these are the critical loci for matching 1, 2
• Additional loci (HLA-DQB1, DRB3/4/5, DPB1) can assist in search strategy design but are optional 1
• Use molecular genotyping methods rather than serological typing to avoid mistyping, particularly important in African American patients 2, 3

Step 2: Search for HLA-Matched Sibling Donors

• HLA-matched siblings are the preferred donor choice due to complete HLA matching, lower graft-versus-host disease rates, and superior transplant-related mortality outcomes 2, 4
• The probability of finding a full HLA match among siblings is only 25% based on Mendelian inheritance patterns 1, 4
• Test all available siblings for HLA compatibility first before proceeding to unrelated donor searches 4

Step 3: Search Unrelated Adult Donor Registries

When no matched sibling is available:

• Access the National Marrow Donor Program (NMDP) in the United States, which serves as the single point of access to nearly 9.5 million donors plus an additional 13 million through World Marrow Donor Association Search and Match 1
• The NMDP's HapLogic algorithm uses allele and haplotype frequency data to predict the probability of high-resolution matches, which is particularly helpful when many potential donors exist 1

Optimal Matching Criteria for Unrelated Donors:

• Seek 8/8 matched donors (high-resolution match at HLA-A, -B, -C, and -DRB1) whenever possible, as this maximizes post-transplantation survival 1, 2
• Each HLA mismatch is associated with approximately 10% lower survival in low-risk disease patients and 5% lower survival in high-risk disease patients 1
• If an 8/8 match is unavailable, a 7/8 matched donor (single-locus mismatch) can be used with acceptable transplant-related mortality risk 1
• Mismatches at HLA-B and -C may be less detrimental than those at HLA-A and -DRB1, though this is not conclusive 1

Search Timeline Considerations:

• For patients with common HLA phenotypes, a suitable donor can usually be identified on the first match run 1
• For patients with uncommon or rare HLA phenotypes who cannot find a match in the worldwide registry pool, waiting for newly recruited donors is not recommended as the likelihood of finding a match is very low 1
• Use search prognosis tools to predict search difficulty early and determine whether to pursue alternative donor sources 1

Step 4: Consider Cord Blood Units

When no adequately matched adult donor is identified:

• Cord blood requires ≥4/6 loci matched for malignant hematological diseases 2
• Cell dose requirements are critical: Total nucleated cells >2.5-4.0 × 10^7/kg and CD34+ cells >1.2-2.0 × 10^5/kg 2
• For adult and larger pediatric patients, cell dose frequently takes priority over HLA match 1, 2
• For children with nonmalignant diagnoses, higher cell doses (≥5 × 10^7/kg) should be selected and HLA matching can take priority 1
• If no adequate single-unit graft is available, a double-unit cord blood transplant is recommended, with units matched at minimum 4/6 loci 1
• Mismatching at 2 or more loci compounds mortality risk, with HLA-C and DRB1 mismatches carrying the highest risk 2

Step 5: Additional Donor Selection Factors

When multiple potential donors exist at the same HLA match level:

• Younger donor age is associated with better overall survival 1
• Consider donor-recipient age ratio, gender matching, ABO compatibility, and CMV IgG serological status 2
• For patients with anti-HLA antibodies and a mismatched allograft, perform antibody specificity analysis or crossmatching prior to transplantation 1

Step 6: Crossmatching Requirements

• Use flow cytometry or complement-dependent cytotoxicity assay for all patients 2
• A positive crossmatch against either T cell or B cell donor targets is a contraindication to transplantation 2

Critical Pitfalls to Avoid

• Non-white patients have lower chances of finding fully matched unrelated donors due to genetic heterogeneity and underrepresentation in donor registries 1, 4
• Do not rely on serological HLA typing alone, as it misses many immunologically functional mismatches identified by high-resolution DNA-based methods 3
• Do not wait indefinitely for a perfect match in patients with rare HLA phenotypes—consider alternative donor sources (cord blood, haploidentical donors) early 1
• For cord blood transplants, balancing cell dose against HLA match is crucial and context-dependent based on patient size and diagnosis 1, 2