Transplantation and Cellular Therapies: HLA, Collection, Manufacturing, and Indications
Core concepts
HLA matching determines transplant compatibility. Class I (A, B, C) on all nucleated cells; Class II (DR, DQ, DP) on antigen-presenting cells. Typing by molecular methods (SSP, SSO, NGS) is standard. Crossmatch (complement-dependent cytotoxicity or flow) detects donor-specific antibodies. HLA antibody screening identifies sensitized patients; virtual crossmatch predicts compatibility.
Hematopoietic stem cell sources: bone marrow, peripheral blood after mobilization (G-CSF), and cord blood. Donor selection considers HLA match, CMV status, age, and weight. Graft-versus-host disease prophylaxis and engraftment monitoring are key.
Cellular therapy manufacturing follows FACT standards and CGMP: collection, processing (washing, volume reduction, cryopreservation with DMSO), labeling (ISBT 128), and storage (vapor-phase nitrogen). Chain of identity and chain of custody are critical. Indications include hematologic malignancies, aplastic anemia, and immune deficiencies.
Traps
- HLA matching stringency differs by transplant type (kidney vs stem cell).
- DMSO toxicity can cause infusion reactions; washing reduces it.
- Cord blood has lower cell dose but less stringent matching.
Rule of thumb
For stem cell transplant, high-resolution HLA matching at A, B, C, DRB1, and DQB1 is standard for unrelated donors; mismatches increase GVHD risk.