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Prospective use of an HCT donor search prognosis algorithm may ensure comparable transplant access regardless of initial search results

April 2023

Researchers presented a study at the European Society for Blood and Marrow Transplantation (EBMT) 49th Annual Meeting that implemented a novel donor search prognosis-based search algorithm into a multicenter trial to improve access to hematopoietic cell transplantation (HCT). The algorithm facilitated comparable incidence of transplantation, regardless of a patient's baseline search prognosis. The results suggest that patients needing allogeneic HCT can be matched with a suitable donor and achieve transplant within the same timeframe using a search prognosis-based search algorithm without a fully matched donor, reducing barriers to care.


Patients requiring allogeneic HCT have a variable likelihood of finding a complete (8/8) HLA-matched unrelated donor (MUD). Prolonging the search for a MUD involves extending the time to transplant and increasing the risk of disease progression and mortality. A search prognosis calculator that uses recipient HLA typing was previously developed by the NMDP to characterize the likelihood of having an available 8/8 MUD but had not been previously evaluated in a large prospective national trial. 

This study was designed to estimate and compare the cumulative incidence of transplant by patient search prognosis score and identify the barriers to transplantation. In this prospective trial, centers committed to following a protocol-defined donor search and selection strategy based on patient search prognosis. 

Study Details

In this randomized clinical trial, centers were instructed to identify 8/8 MUD donors for patients with a greater than 90% 8/8 MUD probability (very likely) search prognosis. Patients with less than 10% 8/8 MUD probability (very unlikely) search prognosis utilized alternative donors (mismatched unrelated, haploidentical, or umbilical cord blood) as a first approach, prioritizing each alternative donor type per investigator discretion. Patients with an intermediate 8/8 MUD probability (less likely) searched for a donor according to individual discretion and were not included in the study.

The cohort included 1755 patients of all ages with no available matched sibling donors from 51 centers. The median patient age was 59 years (range 1-81 years), and diagnoses included acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma, severe aplastic anemia or sickle cell disease. 


More than half of the patients in the cohort achieved HCT (N=1140, 65%). However, 19% of patients died without HCT (N=331), and 16% remained alive without HCT (N=284). The search prognosis arm assignment resulted in 55% very likely (N=958), 30% less likely (N=518), and 16% very unlikely (N=279) cases. Compliance with the protocol-defined donor selection algorithm was excellent, as 94% of the very likely group transplanted utilized 8/8 MUD donors, and 84% of the very unlikely group transplanted used alternative donors (most commonly haploidentical at 58%, then MMUD 19% and cord blood 7%). 

The adjusted cumulative incidence of HCT at 6 months was 59.9% very likely vs. 51.9% very unlikely, and at 2 years, it was 70.5% vs. 65.3%, respectively, as shown in the figure below. Patient age, performance status, disease, and remission status were significantly associated with not achieving HCT. 

Key Takeaways 

This novel study demonstrated that a donor search prognosis-based algorithm can be implemented in a national multicenter trial. It enabled rapid alternative donor prioritization and comparable rates of HCT in very unlikely search prognosis patients with a historically low likelihood of achieving HCT. Donor selection recommendations should focus on donor options that are highly likely to be available for patients to facilitate timely selection, reducing the risk of disease progression. These study results suggest a new era in donor search strategy to enhance equitable access to HCT as a curative therapy. 

Figure 1. Adjusted cumulative incidence of HCT by donor search prognosis

Line chart showing adjusted cumulative incidence of HCT by donor search prognosis over 24 months

Dehn J et al., EMBT abstract pending publication in Bone Marrow Transplantation