Hematopoietic Stem Cell Transplantation (HSCT): What Are Fully Matched, Haploidentical, Unrelated Donors...?

Hematopoietic Stem Cell Transplantation (HSCT) is an effective treatment for malignant hematological tumors. One of the key factors determining the success of HSCT is Human Leukocyte Antigen (HLA) matching. If the HLA of the donor and the patient (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 hematopoietic cells and immune cells. They can not only differentiate into red blood cells, white blood cells, and platelets but also cross-system differentiate into cells of various tissues and organs. HSCs possess three key potentials: self-renewal, multi-directional differentiation, and homing (i.e., directional migration to hematopoietic tissues and organs).

HSCs have two important characteristics: first, a high capacity for self-renewal or self-replication; second, multi-directional differentiation potential to develop into all types of blood cells. Therefore, 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 is a therapeutic method that rebuilds the patient’s normal hematopoietic and immune systems through intravenous infusion of hematopoietic stem and progenitor cells, thereby treating a series of diseases. This procedure replaces the patient’s damaged hematopoietic stem cells with new ones to restore hematopoietic and immune functions for disease treatment. 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 allogenic antigen recognized by the body’s immune system. Almost no two individuals in the population have identical HLA (except identical twins). In addition to organ transplantation, HLA typing is also associated with various diseases including autoimmune diseases, infectious diseases, cancer, and adverse drug reactions.

HLA genes are roughly classified into three categories:

· HLA Class I genes (mainly related to the occurrence of rejection reactions);

· HLA Class II genes (mainly related to the occurrence of 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 including A, B, C, DR, DP, and DQ (as shown in the figure below). Each locus expresses 2 antigens, inherited from each parent respectively. 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 loci to examine. Some hospitals may perform low-resolution or medium-resolution matching based on whether the donor and recipient are blood relatives, which requires testing 6 loci across 3 genes.

Allogeneic HSCT can be classified based on "blood relationship between donor and recipient" and "degree of HLA matching":

1. Classification by Blood Relationship Between Donor and Recipient

· Related Donor: A donor with a blood relationship to the recipient, which can be siblings (sibling donors), direct relatives such as parents, children, grandparents, or grandchildren, as well as collateral relatives. Under the same conditions, direct relatives are preferred.

· Unrelated Donor: A donor with no blood relationship to the recipient, mainly sourced from the China Marrow Donor Program.

2. Classification by Degree of HLA Matching

· Fully Matched Donor: High-resolution HLA matching shows complete identity between the donor and recipient, referred to as "10/10 matching".

· Haploidentical Donor (Half-Matched Donor): HLA matching between the donor and recipient is only partially compatible, with at least 3 loci matching.

3. Donor Selection Considerations

Donor selection requires simultaneous consideration of blood relationship and HLA matching degree:

· Related Fully Matched Donor: Blood-related donor with complete HLA matching, most commonly sibling fully matched donors.

· Related Haploidentical Donor: Blood-related donor with HLA matching of only one chromosome locus (i.e., "haploid").

· Unrelated Donor: Non-blood-related donor. For recipients with an expected long survival time, priority is given to donors with full matching at all 10 HLA loci. For high-risk recipients in the progressive stage of the disease (where the primary disease may be life-threatening), donor selection criteria can be relaxed to select donors with 1-2 mismatched loci for urgent transplantation.

In addition, transplantation also considers factors such as the donor’s gender and age, blood type compatibility between donor and recipient, and the presence of donor-specific antibodies in the patient’s body. Therefore, donor selection requires case-by-case analysis!