Donor and cord blood unit selection guidelines

Considerations for selecting donors and cord blood units for allogeneic HCT

When a patient has an allogeneic hematopoietic cell transplant (alloHCT), multiple patient and donor factors can impact outcomes. Guidelines summarizing current evidence-based research provide a foundation for clinicians during the search and selection of adult donors and umbilical cord blood units (CBU) for alloHCT.

In recent years, donor selection strategies have evolved thanks to advances in graft-versus-host disease (GVHD) prophylaxis, supportive care and search strategies. A panel of multidisciplinary experts convened by CIBMTR^® (Center for International Blood and Marrow Transplant Research^®), a research collaboration between the Medical College of Wisconsin^® and NMDP^SM, reviewed clinical research to provide enhanced considerations for selecting donors for alloHCT in the modern era.¹

Explore the guidelines below and download Donor selection guidelines: A 2025 update as quick reference for your transplant center.

Allogeneic HCT donor search strategy: progressing beyond a hierarchical search algorithm

For patients who receive post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis, the outcomes of HCT with mismatched unrelated (MMUD) or related haploidentical (haplo) donors have improved. As a result, these alternative donor types should be considered early in the search process along with non-HLA factors such as donor age.

Graph displaying the allogenic HCT donor search strategy

Improving search efficiency

The BMT CTN 1702 interventional and observational trial found that considering a patient’s search prognosis—the likelihood of having an available 8/8 matched unrelated donor (MUD)—helps facilitate HCT rates and time to HCT for patients less likely to find a MUD based on their HLA type and ancestry.2 The Search Prognosis Calculator is a helpful tool to help you understand the likely search outcome. Or reach out to the NMDP Clinical HLA Services team at search-strategies@nmdp.org for support.

Use the Allogeneic HCT donor search strategy flowchart to help guide your donor searches at key decision-making moments.

View the flowchart and download

Key considerations for unrelated donor and CBU selection

Donor and CBU selection are highly individualized decisions that should dynamically consider many factors in the context of a patient’s clinical picture and the availability of a matched sibling donor or an 8/8 MUD.

Some donor selection considerations differ if calcineurin inhibitor (CNI-) or PTCy-based GVHD prevention is used. In the PTCy setting, more data is needed to issue definitive guidance for prioritization of specific HLA mismatches. Continued research will help refine these guidelines and address remaining gaps.

Interpret the considerations as guidance rather than a strict step-by-step set of recommendations.

Selection considerations

Selection considerations for PTCy-based GVHD prophylaxis settings

Donor specific antibodies (DSAs)	Does the patient have anti-HLA antibodies? Avoid donors with mismatched alleles targeted by the patient’s DSAs.
Research	Consider clinical trial enrollment whenever appropriate.
HLA match (HLA-A, -B, -C and -DRB1)	Select donors matched at HLA-A, -B, -C and –DRB1 (8/8 match), if likely to be available. Avoid prolonged donor search to find an 8/8 MUD. See the Allogeneic HCT donor search strategy flowchart above.	If 8/8 not likely to be available, recommend evaluation of alternative donor sources. Note that outcomes of 8/8 and 7/8-matched HCT are similar in this setting. If no 7/8 available, donors matched at <7 alleles (HLA-A, -B, -C and -DRB1, 4-6/8 match) can be considered, optimally on a clinical trial.
Age	Select younger aged donors (<31 years). Age may be considered concurrently with availability and match.
ABO	Select donors that are ABO matched when available.
DPB1	Current data does not support prioritization.
Low expression loci (LEL)	No data to support prioritization.
Direction of mismatch	No data to support prioritization.
Other	Consider donor parity, donor center location, weight difference between patient and donor, etc.

Selection considerations for CNI-based GVHD prophylaxis settings

Donor specific antibodies (DSAs)	Does the patient have anti-HLA antibodies? Avoid donors with mismatched alleles targeted by the patient’s DSAs.
Research	Consider clinical trial enrollment whenever appropriate.
HLA match (HLA-A, -B, -C and -DRB1)	Select donors matched at HLA-A, -B, -C and –DRB1 (8/8 match. Avoid prolonged donor search to find an 8/8 MUD. See the Allogeneic HCT donor search strategy flowchart above.	If 8/8 not likely, select donors with *HLA-C03:03 vs. C03:04* mismatch, if present.	≤7/8 match is not recommended in CNI only environment, recommend consideration of alternative GVHD prophylaxis strategies.
Age	Select younger aged donors (<31 years).
DPB1	Select donors matched or permissively mismatched at HLA-DPB1.
Low expression loci (LEL)	Select donors with fewer mismatches at LEL (HLA-DRB3/4/5, DQB1, DPB1).
Direction of mismatch	For 7/8, select donors mismatched at the patient’s homozygous locus (host vs. graft vector only mismatch).
ABO	Select donors that are ABO matched when available.
Other	Consider donor parity, donor center location, weight difference between patient and donor, etc.

Unrelated cord blood unit selection guidelines

Bank practices	Guidelines
Attached segment identity testing	Mandatory
Use of RBC-replete units^a,b	Not recommended
Cryovolume^c	Should be considered, especially if the unit is to be diluted post thaw
Year of cryopreservation	More recent units may be linked to optimal banking practices depending on the bank
Bank location	Domestic or international units fulfilling selection criteria
Bank accreditation and/or licensure	Should be considered
HLA match	Guidelines
Resolution of HLA-typing	Minimum of 8 high-resolution (HLA-A, -B, -C, -DRB1) for both patient and CBU
Donor-recipient HLA-match	≥4/6 HLA-A, -B antigen, -DRB1 high-resolution (traditional match) and ≥4/8 high-resolution match (Some centers investigating use of 4/6 and 3/8 units if adequate dose)
Unit-unit HLA-match for double unit CBT	Not required
Avoidance of units against which recipient has DSA^d	Conflicting results in hematological malignancies; avoid if non-malignant diagnosis
Cryopreserved Cell Dose^e,^f,g	Guidelines
Single unit CBT: minimum dose/kg	TNC ≥2.5 x 107/kg and CD34+ cells ≥1.5 x 105/kg (Some centers recommend higher CD34+ dose as minimum)
Double unit CBT: minimum dose/kg/unit	TNC ≥ 1.5 x 107/kg for each unit and CD34+ cells ≥1.0 x 105/kg for each unit (Some centers recommend higher CD34+ doses for each unit as minimum)

Republished with permission of American Society of Hematology, from Blood, Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR. Dehn J, et al. 134(12), 2019; permission conveyed through Copyright Clearance Center, Inc.

^a RBC-replete units have been associated with life-threatening infusion reactions. Washing is difficult due to the lack of a clear interface after centrifugation; washing also risks cell loss. Therefore, RBC-replete units should be used with caution. They should only be considered in the absence of RBC-depleted CBUs meeting acceptable criteria.

^b Incorporation of nucleated red cell content in unit selection is not recommended at this time.

^c Some expert centers prefer to use an RBC-depleted unit that has a post-cryopreservation volume of 25 mL/bag. If a unit was divided into two bags for storage, then each bag should contain ∼25 mL.

^d Regarding the significance of HLA antibodies, donor-specific antibodies (DSAs) must be considered on a case-by-case basis based on diagnosis and prior immunosuppressive therapy that determine rejection risk, the intensity of planned conditioning, and the number, titer, specificity and complement fixation of DSAs. DSA-targeted units should be avoided in nonmalignant diagnoses. In patients with malignancies, avoid if possible, but use caution if avoidance of units against which the patient has antibodies compromises the selected CBU dose and HLA match.

^e For single- vs. double-unit cord bloodtransplant, if no adequate single-unit graft is available, then a double-unit graft is recommended. Clinical trials investigating the addition of other cellular products to a single-unit graft can also be considered.

^f For prioritization of cell dose vs. HLA match (applies to single- and double-unit transplants), cell dose frequently needs to take priority over HLA match for adult and larger pediatric patients. HLA-match can take priority in children or smaller adults or those with common HLA typing who have multiple units with high cell dose. Optimizing HLA-match is very important in cord blood transplant for nonmalignant diagnoses. In children with nonmalignant diagnoses, higher cell doses (≥5 × 107/kg) should be selected. Further data are required as to how to balance cell dose against HLA match. A current guidance for consideration is as follows: if high doses (e.g., TNC ≥3 × 107/kg and CD34+ ≥2 × 105/kg), consider optimizing high-resolution HLA match over cell dose; if lower TNC and CD34+ doses, optimize dose first and high-resolution HLA match second; and if units have similar cell doses, optimize high-resolution HLA match.

^g Reporting of unit viability testing is not fully standardized. Flow-based assays of CD34+ cell viability on a segment can be informative but have not been validated in multiple banks/centers. NMDP will facilitate discussion between centers and the bank if questions concerning viability testing arise.

Best practices in cord blood selection from six experienced U.S. transplant centers is available as a practical how-to guide for cord blood unit selection and was published by Barker et al. on behalf of the American Society for Transplantation and Cellular Therapy (ASTCT) and NMDP.

These guidelines shed new light on the rapidly evolving transplant landscape and empower health care professionals to move faster and focus on giving patients the best chance at survival.”

STEVEN DEVINE, MD

Guidelines co-author | Chief Medical Officer, NMDP | Senior Scientific Director, CIBMTR

Timing for patient and family member HLA typing

If allogeneic transplant is an option, high-resolution HLA typing of the patient and potential family donors and a preliminary search of the NMDP Registry^SM should be completed early after diagnosis. Patients should also be screened for the presence of anti-HLA antibodies to avoid selection of potential donors carrying donor specific antibody targets.

This is especially important in acute diseases such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) due to the possibility that patients may experience rapid disease progression and will therefore need to proceed to transplant quickly.

HCT consultation timing guidelines developed jointly by NMDP and the ASTCT recommend high-resolution HLA tissue typing at diagnosis for adult and pediatric patients with AML, adults with myelodysplastic syndromes and adolescent and adults with ALL.

Get assistance from the NMDP Clinical HLA Services team

For help assessing the availability of 8/8 matched donors and alternative cell source options, reach out to the NMDP Clinical HLA Services team at search-strategies@nmdp.org.

References

Jimenez Jimenez AM, Spellman SR, Politikos I, et al. Allogeneic hematopoietic cell donor selection: contemporary guidelines from the NMDP/CIBMTR. Transpl Cell Ther. 2025: S2666-6367(25)01290-4. doi:10.1016/j.jtct.2025.07.004
Dehn JG, Logan B, Shaw BE, et al. Access to allogeneic cell transplantation based on donor search prognosis: an interventional trial. medrxiv. 2024.09.16.24313494v1. doi:10.1101/2024.09.16.24313494

Donor and cord blood unit selection guidelines

Considerations for selecting donors and cord blood units for allogeneic HCT

Allogeneic HCT donor search strategy: progressing beyond a hierarchical search algorithm

Improving search efficiency

Key considerations for unrelated donor and CBU selection

Selection considerations

PTCy-based GVHD prophylaxis settings

Selection considerations for PTCy-based GVHD prophylaxis settings

CNI-based GVHD prophylaxis settings

Selection considerations for CNI-based GVHD prophylaxis settings

Cord blood units

Unrelated cord blood unit selection guidelines

Timing for patient and family member HLA typing

Get assistance from the NMDP Clinical HLA Services team

References

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