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[Preprint]. 2024 Sep 16:2024.09.16.24313494.
doi: 10.1101/2024.09.16.24313494.

Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: An Interventional Trial

Jason G Dehn  1 , Brent Logan  2   3 , Bronwen E Shaw  2 , Steven Devine  1   4 , Stefan O Ciurea  5 , Mary Horowitz  2 , Naya He  2 , Iskra Pusic  6 , Samer A Srour  7 , Sally Arai  8 , Mark Juckett  9 , Joseph Uberti  10 , LaQuisa Hill  11 , Sumithira Vasu  12 , William J Hogan  13 , Brandon Hayes-Lattin  14 , Peter Westervelt  15 , Asad Bashey  16 , Nosha Farhadfar  17 , Michael R Grunwald  18 , Eric Leifer  19 , Heather Symons  20 , Ayman Saad  21 , Jenny Vogel  4 , Connor Erickson  4 , Kelly Buck  1 , Stephanie J Lee  22 , Joseph Pidala  23
Affiliations

Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: An Interventional Trial

Jason G Dehn et al. medRxiv. .

Abstract

Importance: Patients requiring allogeneic hematopoietic cell transplantation have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor. A Search Prognosis calculator can estimate the likelihood.

Objective: To determine if using a search algorithm based on donor search prognosis can result in similar incidence of transplant between patients Very Likely (>90%) vs Very Unlikely (<10%) to have a matched unrelated donor.

Design: This interventional trial utilized a Search Prognosis-based biologic assignment algorithm to guide donor selection. Trial enrollment from June 13, 2019-May 13, 2022; analysis of data as of September 7, 2023 with median follow-up post-evaluability of 14.5 months.

Settings: National multi-center Blood and Marrow Transplantation Clinical Trials Network 1702 study of US participating transplant centers.

Participants: Acute myeloid and lymphoid leukemias, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphomas, severe aplastic anemia, and sickle cell disease patients referred to participating transplant centers were invited to participate. 2225 patients were enrolled and 1751 were declared evaluable for this study. Patients were declared evaluable once it was determined no suitable HLA-matched related donor was available.

Intervention: Patients assigned to the Very Likely arm were to proceed with matched unrelated donor, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (~25%) to find a matched unrelated donor, were observed under standard center practices, but were not part of the primary objective.

Main outcome: Cumulative incidence of transplantation by Search Prognosis arm.

Results: Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Search prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely and 276 (16%) Very Unlikely. 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1,234 patients, the adjusted cumulative incidence (95% CI) of HCT at 6-months was 59.8% (56.7-62.8) in the Very Likely group versus 52.3% (46.1-58.5) in the Very Unlikely (P=0.113).

Conclusions: A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial. This approach resulted in rapid alternative donor identification and comparable rates of HCT in patients Very Likely and Very Unlikely to find a matched unrelated donor.

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Conflict of interest statement

CONFLICT-OF-INTEREST DISCLOSURE: S.J.L- Board of Directors, nmdp (uncompensated) A.S.-Consulting Fees: Sanofi and Therakos

Figures

Figure 1:
Figure 1:. Cumulative Incidence of Transplant
a) Unadjusted Cumulative Incidence of Transplant by Search Prognosis Arm Graph shows the unadjusted cumulative incidence of hematopoietic cell transplant over time from patient evaluability. b) Adjusted Cumulative Incidence of Transplant by Donor Search Prognosis Arm Graph shows the adjusted cumulative incidence of hematopoietic cell transplant by Search Prognosis arm over time from patient evaluability; Very Likely and Very Unlikely.
Figure 1:
Figure 1:. Cumulative Incidence of Transplant
a) Unadjusted Cumulative Incidence of Transplant by Search Prognosis Arm Graph shows the unadjusted cumulative incidence of hematopoietic cell transplant over time from patient evaluability. b) Adjusted Cumulative Incidence of Transplant by Donor Search Prognosis Arm Graph shows the adjusted cumulative incidence of hematopoietic cell transplant by Search Prognosis arm over time from patient evaluability; Very Likely and Very Unlikely.
Figure 2:
Figure 2:. Time from Evaluability to Transplant Among Transplanted Patients
Graph shows the cumulative incidence of transplant by infused donor type for patients who reach transplant. UCB=umbilical cord blood; MUD= matched unrelated donor; MMUD=mismatched unrelated donor; Haplo=haploidentical related donor
Figure 3:
Figure 3:. First Preference of Donor Cell Source by Year of Enrollment
Graph shows the reported first ranked donor cell source at enrollment by year. Mismatched unrelated donor (MMUD), haploidentical related (Haplo) and Umbilical Cord Blood (UCB), No donor cell alternatives reported (None) and Missing are shown.
See this image and copyright information in PMC

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