HSCT Explained: Fully Matched, Haploidentical, and Unrelated Donors

Hematopoietic Stem Cell Transplantation (HSCT) is an effective treatment for malignant hematological tumors. One key factor determining its success is Human Leukocyte Antigen (HLA) matching. If the HLA of the donor and the recipient do not match, severe rejection may occur, even endangering life.

I. What Are Hematopoietic Stem Cells?

Hematopoietic Stem Cells (HSCs) are immature cells that serve as the origin of all blood and immune cells. They can differentiate into red blood cells, white blood cells, and platelets, and even cross-system differentiate into cells of various tissues and organs. HSCs have three key potentials: self-renewal, multi-directional differentiation, and homing (directional migration to hematopoietic tissues and organs). Because of their high self-renewal capacity and multi-directional differentiation potential, they are multifunctional stem cells, medically known as "universal cells" and the progenitor cells of the human body.

II. What Is Hematopoietic Stem Cell Transplantation?

HSCT rebuilds the patient's normal hematopoietic and immune systems through intravenous infusion of hematopoietic stem and progenitor cells. It replaces the patient's damaged stem cells with new ones to restore hematopoietic and immune function. Currently, HSCT is the only curative method for most hematological diseases such as leukemia and severe aplastic anemia.

III. HLA Matching

Human Leukocyte Antigen (HLA) is a highly polymorphic allograft antigen and the main allogeneic antigen recognized by the immune system. Almost no two individuals have identical HLA (except identical twins). Beyond transplantation, HLA typing is associated with autoimmune diseases, infectious diseases, cancer, and adverse drug reactions.

HLA genes fall into three categories:

• HLA Class I genes (mainly related to rejection reactions)
• HLA Class II genes (mainly related to immune responses)
• HLA Class III genes (encoding certain complements, cytokines, heat shock proteins, etc.)

Similar to blood-type classification (A, B, AB, O), HLA matching involves 6 loci: Class I antigens (A, B, C) and Class II antigens (DP, DQ, DR). HLA genes are located on chromosome 6, with six well-studied loci: A, B, C, DR, DP, and DQ. Each locus expresses 2 antigens, inherited from each parent. Therefore, related-donor transplantation has a lower risk of postoperative rejection.

High-resolution HLA matching typically involves 5 loci (A, B, C, DR, DQ), each with two alleles, totaling 10 to examine. Some hospitals may perform low- or medium-resolution matching depending on whether donor and recipient are blood relatives, requiring testing of 6 loci across 3 genes.

Allogeneic HSCT can be classified by "blood relationship" and "degree of HLA matching."

1. By Blood Relationship

• Related Donor: A donor with a blood relationship to the recipient, such as siblings (sibling donors), direct relatives (parents, children, grandparents, grandchildren), or collateral relatives. Under the same conditions, direct relatives are preferred.
• Unrelated Donor: A donor with no blood relationship, mainly sourced from the China Marrow Donor Program.

2. By Degree of HLA Matching

• Fully Matched Donor: High-resolution HLA matching shows complete identity, referred to as "10/10 matching."
• Haploidentical Donor (Half-Matched): HLA matching is only partially compatible, with at least 3 loci matching.

3. Donor Selection Considerations

Donor selection requires considering both blood relationship and HLA matching:

• Related Fully Matched Donor: Blood-related donor with complete HLA matching, most commonly a sibling.
• Related Haploidentical Donor: Blood-related donor matching only one chromosome locus (i.e., "haploid").
• Unrelated Donor: For recipients with expected long survival, priority goes to donors fully matched at all 10 HLA loci. For high-risk recipients in a progressive disease stage (where the primary disease may be life-threatening), selection criteria can be relaxed to 1-2 mismatched loci for urgent transplantation.

Transplantation also considers the donor's gender and age, blood-type compatibility, and the presence of donor-specific antibodies in the patient. Therefore, donor selection requires case-by-case analysis.