---
title: "Dr. Tong Wu: How Donors Are Selected for Allogeneic Hematopoietic Stem Cell Transplantation"
url: "https://www.yyhmedical.com/en/news/allogeneic-stem-cell-transplant-donor-selection-guide"
type: Article
inLanguage: en-US
category: Expert Insights
datePublished: 2026-06-12
---

# Dr. Tong Wu: How Donors Are Selected for Allogeneic Hematopoietic Stem Cell Transplantation

> Dr. Tong Wu explains five key factors in donor selection for allogeneic hematopoietic stem cell transplantation: HLA matching, non-HLA factors, hematopoietic and immune function, inherited predisposition, and personal and family medical history.

Summary: Donor selection can directly affect outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dr. Tong Wu of Beijing GoBroad Boren Hospital explains five major areas that should be considered: matching at 10 HLA alleles across HLA-A, -B, -C, -DR, and -DQ; non-HLA factors such as donor age, CMV/EBV serostatus, sex, blood type, stem cell source and cell dose, and donor-specific HLA antibodies (DSA); the donor's hematopoietic and immune function; screening for inherited predisposition variants that may affect engraftment or increase the risk of donor-derived leukemia; and review of the donor's personal and family medical history. The article also outlines the usual order of donor preference and considerations for different disease settings.

  

*For patients preparing for allogeneic hematopoietic stem cell transplantation, choosing the right donor is an important part of the treatment plan and can influence transplant outcomes. Patients and families often have many questions about how donors are evaluated and prioritized. In this article, Dr. Tong Wu of Beijing GoBroad Boren Hospital explains the core principles and major factors involved in donor selection.*

Allogeneic hematopoietic stem cell transplantation is used mainly for two broad groups of conditions. The first includes hematologic malignancies such as leukemia, myelodysplastic syndromes, lymphoma, and myeloma. The second includes nonmalignant disorders such as aplastic anemia and congenital immunodeficiency disorders.

Five major factors are considered when selecting a donor for allogeneic hematopoietic stem cell transplantation:

◆ HLA matching

◆ Non-HLA factors

◆ Hematopoietic and immune function

◆ Inherited genetic predisposition

◆ Personal and family medical history

**1\. HLA Matching**

Before transplantation, HLA typing usually includes HLA-A, -B, -C, -DR, and -DQ. Because each locus has two alleles, this is commonly referred to as a 10/10 HLA match.

A donor who matches at all 10 alleles is considered fully matched. A fully matched donor is often a sibling, although a 10/10 matched unrelated donor may also be identified through a donor registry. In some cases, a 9/10 matched unrelated donor may also be considered for transplantation.

According to data from the Center for International Blood and Marrow Transplant Research (CIBMTR), each additional HLA mismatch in unrelated donor transplantation is associated with an approximately 10% reduction in post-transplant survival.

In experienced transplant centers, outcomes with a matched sibling donor and a haploidentical related donor can be comparable.

**2\. Non-HLA Factors**

If several donors meet the HLA requirements, how should the team choose among them?

  

-   Age: Donor age is one of the most important considerations after HLA matching. In unrelated donor transplantation, a donor who is 10 years younger has been associated with an approximately 3% improvement in survival.
    
      
    
-   Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) serostatus: Ideally, donor and recipient CMV IgG and EBV IgG status should be aligned. For example, a CMV IgG-positive patient would preferably receive cells from a CMV IgG-positive donor.
    
      
    
-   Sex: A female donor for a male recipient may increase the risk of graft-versus-host disease (GVHD), and a female donor with multiple prior pregnancies may increase GVHD risk in both male and female recipients. In pediatric haploidentical transplantation, a mother may be preferred over a father in some settings, which has been linked to long-term bidirectional microchimerism established during pregnancy.
    
      
    
-   ABO blood type: Donor-recipient ABO incompatibility usually has a limited effect on overall transplant outcomes and can often be managed by appropriate graft processing, such as red blood cell or plasma depletion. However, ABO mismatch may be associated with delayed hemolysis, delayed red-cell engraftment, or pure red cell aplasia.
    
      
    
-   Stem cell source and cell dose: Stem cells may come from bone marrow (BM), peripheral blood stem cells (PBSCs), or umbilical cord blood. BM and PBSC transplantation can achieve similar survival outcomes. PBSCs generally engraft more quickly but are associated with a higher risk of chronic GVHD. An adequate stem cell dose is important for transplant outcomes. The article recommends more than 3 × 10^6 CD34+ cells/kg for PBSC grafts and more than 0.2 × 10^6 CD34+ cells/kg for cord blood grafts.
    
      
    
-   HLA antibodies: Some patients have donor-specific HLA antibodies (DSA) in their serum. Testing is especially important when the donor and recipient are not fully HLA matched. A positive DSA result increases the risk of graft failure and may reduce post-transplant survival. If the only available donor is DSA-positive, antibody-reduction treatment may be needed before transplantation.
    

A commonly used international order of donor preference is: first, a matched sibling donor; second, a fully matched unrelated donor; and then a 9/10 matched unrelated donor, a haploidentical related donor, or cord blood, depending on the clinical situation.![e708db67-0f31-4270-8621-a77e1f3bc5c6.png](https://gaobo-byh-h5.oss-accelerate.aliyuncs.com/images/20260913/9639e3f91609a7a953d35b92f387a186_20260913222540.png "9639e3f91609a7a953d35b92f387a186_20260913222540.png") 

**3\. Hematopoietic and Immune Function**

Transplantation rebuilds the recipient's hematopoietic and immune systems using cells from the donor. For this reason, the health and function of the donor's blood-forming and immune systems are important to transplant outcomes.

**How can these functions be assessed?**

Hematopoietic function can be evaluated through a complete blood count, bone marrow cellularity, and the proportion of CD34+ cells in the bone marrow. Immune function may be assessed through lymphocyte subsets, immunoglobulin levels, and markers such as granzyme and perforin in NK cells.

**4\. Inherited Genetic Predisposition**

Mutations acquired by tumor cells are called somatic mutations, while inherited or constitutional variants are referred to as germline variants.

Some inherited predisposition variants can increase a person's risk of developing hematologic malignancies or solid tumors. In general, variants with a greater functional impact may be associated with disease developing at a younger age.

If a donor carries a clinically significant inherited predisposition variant, using that donor's stem cells may be associated with poor stem cell mobilization, graft failure, poor graft function, or, in rare cases, donor-derived leukemia.

**5\. Personal and Family Medical History**

Many people carry genetic variants of one kind or another. The key question is whether those variants have meaningful functional effects. This is one reason a careful personal and family medical history is important when evaluating a potential donor.

Some people may consider themselves healthy because they have no major illness, while also having conditions such as asthma, hyperthyroidism, or psoriasis. These conditions may involve immune dysregulation and can be relevant when assessing whether someone is an appropriate donor.

Family history is reviewed for clustering of cancers or immune-related diseases, a history of infectious diseases, unexplained childhood deaths, and consanguinity, among other factors.

**Summary**

◆ A matched sibling donor is generally the first choice.

◆ For hematologic malignancies, matched unrelated and matched sibling donor transplantation can achieve similar disease-free survival. Among non-HLA factors in unrelated donor transplantation, donor age is particularly important, with younger donors generally associated with better outcomes.

◆ When choosing among a haploidentical related donor, a mismatched unrelated donor, and cord blood, the decision depends on the transplant center's experience, how urgently transplantation is needed, donor age, and DSA status.

◆ For nonmalignant hematologic diseases, bone marrow is generally preferred as the stem cell source because it is associated with less chronic GVHD and may support better long-term quality of life.

◆ In adults with hematologic malignancies, bone marrow and PBSC transplantation can achieve similar survival outcomes.

◆ Selecting a donor with healthy hematopoietic and immune function and a favorable inherited genetic background can support post-transplant hematopoietic and immune recovery and may reduce complications such as GVHD, infection, and relapse, helping improve long-term disease-free survival.

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