What is HLA (Human Leukocyte Antigen) typing in the context of a patient with severe leukopenia, bone marrow failure, and severe thrombocytopenia?

What is HLA Typing?

HLA typing is a laboratory test that identifies specific genetic markers (Human Leukocyte Antigens) on cell surfaces to match donors and recipients for hematopoietic stem cell transplantation, and in patients with severe cytopenias, it serves two critical purposes: identifying potential transplant donors and selecting compatible platelet products for those requiring frequent transfusions. 1

Primary Clinical Applications in Bone Marrow Failure

For Transplant Evaluation

• All patients with newly diagnosed bone marrow failure syndromes who are potential transplant candidates should undergo HLA typing immediately 1
• For patients with myelodysplastic syndrome (MDS) at intermediate-1, intermediate-2, or high IPSS risk who are eligible for allogeneic stem cell transplant, HLA typing is recommended 1
• HLA typing should be performed for patients aged under 65 years with bone marrow failure to assess transplant eligibility 1
• The test identifies whether a fully HLA-matched sibling donor exists, which represents the optimal donor source for potentially curative transplantation 1

For Platelet Transfusion Management

• For patients requiring platelet transfusions due to severe thrombocytopenia, HLA typing (specifically HLA-A and HLA-B) helps prevent platelet refractoriness from alloimmunization 1
• This is particularly important when patients need repeated platelet transfusions, as HLA antibodies can develop and render standard platelet transfusions ineffective 1, 2

Technical Specifications

Standard Testing Protocol

• Patients and potential donors should be typed by DNA-based methods at high resolution for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DPB1 loci 1
• High-resolution typing (also called allele-level or 2-field typing) discriminates among HLA genes that encode proteins differing in amino acid sequences of their antigen recognition domains 1
• Additional loci (HLA-DQB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DPA1) may assist in efficient donor searches and selection among multiple similar donors 1

For Family Member Evaluation

• HLA typing of siblings and family members should be performed early to identify matched sibling donors 1
• For patients up to age 80 years (or per institutional practice) without favorable-risk cytogenetics, tissue typing should be broadened to include alternative donor searches 1
• Less than 33% of patients have an HLA-matched sibling donor, making early typing of all potential family donors critical 2

Clinical Decision Points

When to Order HLA Typing

• Immediately at diagnosis for any patient with severe bone marrow failure (severe leukopenia, thrombocytopenia, or aplastic anemia) who is under 65-80 years old 1
• Before initiating multiple platelet transfusions in patients with severe thrombocytopenia to enable HLA-matched platelet selection if refractoriness develops 1
• During induction chemotherapy for patients with non-favorable risk disease, rather than waiting for remission 1

Impact on Transplant Outcomes

• HLA-mismatching between donors and recipients is consistently associated with inferior recipient survival, increased graft-versus-host disease, and higher transplant-related mortality 1
• An 8/8 HLA match (HLA-A, B, C, DRB1) represents the optimal donor selection criterion 1
• Even single allele mismatches significantly impact outcomes, making precise high-resolution typing essential 1

Common Pitfalls to Avoid

• Do not delay HLA typing until after initial treatment response is assessed—typing should occur at diagnosis for any transplant-eligible patient 1
• Do not use low-resolution typing methods—only high-resolution DNA-based typing provides adequate precision for modern transplant matching 1, 3
• Do not forget to type all siblings simultaneously—sequential typing delays donor identification and transplant timing 1
• Avoid ordering HLA typing for platelet matching in patients unlikely to need repeated transfusions, as the cost may not be justified 1