Foundations of Transplant · 3 min read
Human Leukocyte Antigen System · Pretransplant Evaluation
The human leukocyte antigen (HLA) system encodes cell surface proteins crucial for immune recognition. HLA genes located on chromosome 6 exhibit extensive polymorphism, making matched donors rare outside identical siblings.
HLA Classes
Class I molecules (HLA-A, HLA-B, HLA-C) present intracellular peptides to CD8+ cytotoxic T cells. Class II molecules (HLA-DR, HLA-DQ, HLA-DP) present extracellular peptides to CD4+ helper T cells. Both classes influence transplant outcomes through alloreactivity.
HLA Typing
Modern typing uses molecular methods including polymerase chain reaction and next-generation sequencing. High-resolution typing identifies specific alleles rather than antigen groups, improving match accuracy. Standard matching evaluates HLA-A, HLA-B, HLA-C, and HLA-DRB1, with 8/8 matching considered optimal for unrelated donors.
Matching Considerations
Each individual inherits one HLA haplotype from each parent, giving 25% probability of HLA-identical sibling donors. Unrelated donor searches through registries like the National Marrow Donor Program identify matches for approximately 70% of Caucasian patients but lower percentages for minority populations.
HLA mismatch increases GVHD, graft failure, and mortality risk. Single antigen or allele mismatches may be acceptable when matched donors are unavailable, with careful consideration of mismatch permissiveness and directional effects.
Comprehensive evaluation ensures transplant candidacy and identifies potential complications. Evaluation encompasses disease assessment, organ function, psychosocial factors, and infectious disease screening.
Disease Assessment
Disease status significantly impacts transplant outcomes. Complete remission generally predicts better survival than active or refractory disease. Evaluation includes bone marrow biopsy, cytogenetics, molecular studies, minimal residual disease testing, and imaging studies appropriate to the diagnosis.
Organ Function Assessment
Cardiac evaluation includes electrocardiogram, echocardiogram measuring ejection fraction, and possibly stress testing for patients with cardiac risk factors. Left ventricular ejection fraction typically must exceed 45-50% for transplant eligibility.
Pulmonary function testing measures forced expiratory volume, forced vital capacity, and diffusing capacity for carbon monoxide. Significant pulmonary impairment increases regimen-related toxicity risk. Adjustments to conditioning intensity or agents may be necessary.
Hepatic evaluation includes liver function tests, hepatitis serologies, and assessment for iron overload in heavily transfused patients. Renal function assessment uses serum creatinine, calculated glomerular filtration rate, and urinalysis.
Infectious Disease Screening
Comprehensive serologic testing identifies latent infections requiring prophylaxis or monitoring. Standard screening includes cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella-zoster virus, hepatitis B and C, HIV, syphilis, and toxoplasmosis. Endemic fungal and parasitic infections are screened based on geographic exposure.
CMV serostatus of donor and recipient significantly impacts posttransplant management. CMV-seronegative recipients receiving CMV-seronegative grafts have lowest reactivation risk. CMV-seropositive recipients require intensive monitoring and preemptive therapy.
Psychosocial Assessment
Social work evaluation assesses support systems, caregiver availability, housing, transportation, financial resources, and insurance coverage. Psychological evaluation identifies depression, anxiety, cognitive impairment, or substance abuse requiring intervention.
Adequate social support correlates with improved adherence, reduced complications, and better survival. Caregiver education addresses the demanding posttransplant period requiring around-the-clock support.
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