National Marrow Donor Program Research Articles

Increasing access to transplantation through telemedicine and patient navigation

BackgroundHematopoietic cell transplantation (HCT) is a promising treatment for hematological diseases, yet access barriers like cost and limited transplant centers persist. Telemedicine-based patient navigation (PN) has emerged as a solution. This study presents a cost-free PN telemedicine clinic (TC) in collaboration with the National Marrow Donor Program. Aim: to assess its feasibility and impac on HCT access determined by the cumulative incidence of transplantation. MethodsIn this single-center cohort study, patients of all ages and diagnoses referred for HCT participated. Two transplant physician-navigators established patient relationships via video calls, collecting medical history, offering HCT education and recommending pretransplant tests. The analysis involved descriptive statistics and intent-to-transplant survival assessment. ResultsOne hundred and three patients were included of whom n = 78 were referred for allogeneic HCT (alloHCT), with a median age of 28 years. The median time from initial contact to the first consult was 5 days. The cumulative incidence of transplantation was 50% at 6 months and 61% at 12 months, with varying outcomes based on HCT type. Notably, 49 patients were not transplanted, primarily due to refractory disease, progression or relapse (57.1%). Autologous HCT candidates and physician referrals were correlated with higher transplant success compared to alloHCT candidates and patients who were not referred by a physician. ConclusionOur pretransplant TC was feasible, facilitating access to HCT. Disease relapse posed a significant barrier. Enhancing timely physician referrals should be a focus for future efforts.

Improving Unrelated Donor Equity: Assessing Mismatched Donor Opportunities with Real-World Data in a Minority-Predominant Cohort

Recent advances in graft-versus-host disease (GVHD) prophylaxis including post-transplant cyclophosphamide (PTCy) and abatacept have significantly improved outcomes following HLA-mismatched allogenic hematopoietic stem cell transplantation (allo-HSCT) and have tremendous potential for reducing racial disparities in donor availability. A recent small study employing bone marrow as the source of stem cells showed similar outcomes after 5/8 versus 7/8 matches and is currently being tested in a larger study using peripheral blood stem cells. In this study, we examine real-world alternative donor HSCT options for a minority-predominant cohort in the Bronx, NY, focusing on the availability of lesser-matched (5/8 to 7/8) donors. Records of patients who underwent HLA typing at Montefiore Medical Center (2019 to 2022) were reviewed. The National Marrow Donor Program registry was queried to evaluate the availability of donors with at least 99% likelihood of HLA match at various levels (5/8, 6/8, 7/8, 8/8). Two hundred forty-one patients were included, 70% were non-White. Although the availability of ≥7/8 donors was less common in non-White patients, 100% of patients from each group had at least one or more 5/8 and 6/8 HLA-matched donors and more than 80% of these patients had >100 potential 5/8 and 6/8 HLA-matched donors. There was no statistical difference by race or ethnicity in the mean number of donors at 5/8 and 6/8 HLA-match levels. We demonstrate through real-world data that patients from diverse ethnic and racial backgrounds have access to 5/8 and 6/8 HLA-matched donors for allo-HSCT, potentially eliminating disparities in donor availability and allowing prioritization of other donor selection characteristics such as donor age, sex, ABO, and B leader matching. Further work is needed to study whether the use of mismatched donors offers a more potent graft-versus malignancy effect and optimal GVHD prophylaxis.

Return to school practices after hematopoietic cell transplantation: a survey of transplant centers in the United States.

To understand transplant center recommendations on return-to-school timing and related support for hematopoietic cell transplant (HCT) survivors, we conducted a two-phase, cross-sectional, web-based survey: In Phase I, medical directors of pediatric HCT centers from the National Marrow Donor Program/ Be The Match Registry were asked regarding the availability of a return to school standardized operating procedure (SOP). In Phase II, HCT physician members of the Pediatric Transplantation and Cellular Therapy Consortium were approached to study inter-physician practice variability regarding return to school post-HCT, factors affecting their decision-making, and support provided by HCT centers for return to school. Out of 46 respondents in Phase I (55% response rate), 28 (61%) reported having a SOP. Wide variations in recommendations were noted in 12 received SOPs. In Phase II, 122 physicians (60 centers) responded (30.6% response rate). The majority (60%) recommended autologous HCT recipients return to school within 6 months post-HCT but 65% recommended allogeneic HCT recipients return to school after 6 months or once off immunosuppression. Our findings indicate a lack of consensus within and across HCT centers regarding recommended return to school timing and underscore need for a guideline to standardize this process to ensure patient safety and re-integration into school.

A Standardized Cell Dose to Optimize Unrelated Donor Peripheral Blood Stem Cell (PBSC) Collections: A Prospective Study between the Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN) and the National Marrow Donor Program (NMDP)

A Standardized Cell Dose to Optimize Unrelated Donor Peripheral Blood Stem Cell (PBSC) Collections: A Prospective Study between the Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN) and the National Marrow Donor Program (NMDP)

Expanding donor options: haploidentical transplant recipients are also highly likely to have a 7/8-matched unrelated donor

AbstractThe use of haploidentical related donor (HRD) hematopoietic cell transplants (HCTs) in the United States grew by more than fourfold in the last decade, driven mainly by use of posttransplant cyclophosphamide (PTCy)-based graft-versus-host-disease prophylaxis. However, not all patients have a suitable HRD available. In this study, we explored the existence of unrelated donors (URDs) on the National Marrow Donor Program (NMDP) registry at the 8/8- or 7/8-match level for patients receiving HRD HCT in the United States and reporting to the Center for International Blood and Marrow Transplant Research between 2013 and 2020. The data consist of 9696 HRD HCT recipients. The NMDP search prognosis score and a search simulation were used to estimate counts of URD matches on the registry. NMDP search prognosis varied by patient ancestry, with 27.5% non-Hispanic White having a good score compared with 4.6% of African American HRD HCT recipients. Overall, 34% of recipients had ≥1 8/8-matched URDs and 84% had ≥1 7/8 URDs. Recipients of older HRDs (≥35 years) had a likelihood of between 20%- 65% of having ≥5 existing 7/8-matched URDs who were aged ≤35 years. Donor-selection practices varied among the 10 highest-volume HRD centers: 6 had >20% chance of an existing 8/8-matched URD for their HRD recipients, whereas 4 centers had low likelihood of identifying an 8/8-matched URD. In conclusion, although most US patients undergoing HRD HCT do not have an existing 8/8 URD, the majority have an existing 7/8-matched URD. Studies comparing outcomes in patients receiving either HRD or 7/8-matched URD HCT and PTCy-based graft-versus-host disease prophylaxis may be warranted.

Trials in Progress: A Phase I/II Clinical Trial of Off the Shelf Universal Donor Natural Killer Cells Combined with Chemotherapy for Treatment of Relapsed/Refractory Acute Myeloid Leukemia (KARMA)

Background and Significance: Natural killer (NK) cells are cytotoxic lymphocytes that play a key role in recognizing malignant cells. In AML, qualitative and quantitative dysfunction of innate NK cells portends a poor prognosis and adoptive NK cell therapy has been shown to be safe and effective with minimal risk for GVHD (Ciurea et al. 2022; Silla et al. 2021). To circumvent cost and logistics restraints of per patient manufacture of NK cells, we developed a universal donor (UD) NK cell bank for “off-the-shelf” NK cells (UD FC21-NK cells). Donors with optimal NK cell characteristics are identified through the National Marrow Donor Program, and peripheral blood NK cells are expanded for two weeks by co-culture with irradiated K562 feeder cells expressing 4-1BB ligand and membrane bound IL-21 as previously described (Denman et al. 2012). We seek to study the safety and efficacy of multiple doses of UD FC21-NK cells combined with fludarabine and cytarabine (FLA) chemotherapy in patients with relapsed or refractory AML. Study Design and Methods: This open label, single-center phase I/II study will include a dose escalation phase to establish safety and determine the recommended phase II dose followed by an expansion phase to estimate efficacy (complete response rate and MRD negative response rate). Up to 20 patients ages 18-25 with relapsed or refractory AML, including isolated extramedullary disease, will be enrolled. Exclusion criteria include active GVHD, uncontrolled infections, hematopoietic stem cell transplant within 3 months of enrollment, and donor lymphocyte infusion within 30 days of enrollment. Patients will undergo FLA chemotherapy followed by six doses of UD FC21-NK cells given thrice weekly for two weeks (Figure 1). Dose levels include 1 x 10 7 UD FC21-NK cells/kg/dose, 3 x 10 7 UD FC21-NK cells/kg/dose, and 1 x 10 8 UD FC21-NK cells/kg/dose. Patients may receive up to 2 cycles if they do not achieve a CR after cycle 1 or if necessary to bridge to transplant. Peripheral blood samples will be drawn weekly for immune correlatives including in vivo NK cell expansion and persistence. The trial is currently open to enrollment to adult patients with the intent to expand to pediatrics after demonstrating preliminary safety. Clinical trial information: NCT05503134

TNC/Kg and CD34+/Kg Cell Dose Impact on Patient Engraftment after Allogeneic Transplant with Conventional Bone Marrow; Better Predictability of Graft Content Needed

Introduction: Bone marrow (BM) harvested from a related (RD) or unrelated donor (URD) remains a viable graft source for patients (pts) receiving an allogeneic hematopoietic stem cell transplant (allo-HCT). However guidance on minimum TNC/kg & CD34+/kg thresholds to optimize engraftment & a method to best predict graft content are needed. Methods: All BM products (prdcts) harvested between 1/1/2016 to 6/30/2023 for adult & pediatric (ped) pts were studied (n= 261). Pt, donor, & BM prdct characteristics were collected. For each BM prdct, pre-processing (pre-proc) data was obtained to determine a median pre-proc TNC, TNC/mL, CD34+/mL, and CD34+/TNC % of all BM prdcts & infused TNC & CD34+ content was also recorded. Pt neutrophil (Neutr) & platelet (Plt) engraftment data was collected with Neutr engraftment defined as the first of 3 consecutive days of an absolute neutr count ≥ 500 x 10^3/μl. Plt engraftment was defined as ≥ 20K/μl plts & transfusion independence for ≥ 7 days. Univariable & multivariable analyses (MVAs) using the Fine and Gray model were performed to assess impact of infused TNC/kg (MVA1), CD34+/kg (MVA2), and CD34+/TNC % (MVA3) of conventional BM prdcts on Neutr (n eval pts = 239) & Plt engraftment (n eval pts = 238). The National Marrow Donor Program's (NMDP) provided estimate for median TNC/mL of BM (0.183 x 10^8) was used w/ donor weight (wt), the NMDP maximum (max) allowable amount of BM (20mL per donor kg), & a standard max BM volume request (1500mL) to calculate an expected pre-proc TNC for all BM prdcts. The expected TNC for small ped pts was limited to (15 * pt wt) to ensure a TNC/kg cell dose of ≤ 15 x 10^8. An expected pre-proc CD34+ for each BM prdct was then calculated by expected TNC x CD34+/TNC % of all BM prdcts on study. An expectation accuracy (EA) % for both TNC & CD34+ was calculated for each BM prdct (expected / actual pre-proc values observed by our center). TNC & CD34+ EA % of BM prdcts collected by other domestic & international centers were analyzed. Results: 261 BM prdcts from 259 donors for 258 pts were studied. The BM prdcts had the following pre-proc medians: TNC/mL of 0.136 x 10^8, CD34+/mL of 0.124 x 10^6, & CD34+/TNC % of 0.96. MSKCC harvested 141 (54%) of the BM prdcts and the rest were facilitated by the NMDP: 71 (27%) from 26 domestic centers and 49 (19%) from 28 international centers. The cumulative incidence of Neutr engraftment was 96% (95% CI 92, 98%) by days +30 and +100 after allo-HCT and for Plts it was 48% (95% CI 42,54%) and 91% (95% CI 87,94%) respectively. Table 1 shows the MVA results testing TNC/kg (MVA1), CD34+/kg (MVA2), CD34+/TNC % (MVA3) & engraftment after allo-HCT w/ conventional BM, indicating Neutr & Plt engraftment is impacted by TNC/kg and CD34+/kg cell dose but not by CD34+/TNC %. In all 3 MVA models, associations were observed for pt diagnosis [SAA w/ better Plt engraftment vs. ref grp], donor type (≤ 7/8 URD or haploidentical RD w/ worse Neutr & Plt engraftment vs. ref grp), donor ABO incompatibility (Minor w/ better Plt engraftment vs. ref grp), and infusion type [cryopreserved (cryo'ed)/thawed w/ worse Neutr engraftment vs. fresh]. The expectation accuracy (EA) analysis (Wilcoxon rank-sum test) of pre-proc TNC & CD34+ is seen in Table 2. The median expected pre-proc TNC (274) & CD34+ (264) of BM prdcts received from domestic centers & international centers were the same. However BM prdcts from international centers had a lower median actual pre-proc TNC (192) & CD34+ (162), a lower median TNC EA of 74% (vs. 89% for dom centers, p=0.008), & a lower median CD34+ EA of 63% (vs. 93% for dom centers, p<0.001). All BM prdcts combined (n = 120) had a median TNC EA of 83% & a median CD34+ EA of 76%. Conclusions: This large analysis suggests BM products with a TNC/kg > 2.0 x 10^8 and a CD34+/kg > 2.0 x10^6 were associated with better Neutr & Plt engraftment, as was allo-HCT with an HLA-matched donor. Cryo'ed products were associated with worse Neutr but not Plt engraftment, while SAA & having a BM graft from a donor with a minor ABO incompatibility were associated with better Plt engraftment. The expectation accuracy analysis suggests BM graft content is often not meeting expectations, highlighting a need for updated guidance on expectations of BM graft content. An update to NMDP's guidance on estimated TNC/mL of BM or analysis and provision of additional data (e.g., median pre-proc CD34+/mL or CD34+/TNC %) could allow centers to better anticipate TNC & CD34+ BM graft content and help guide donor & graft selection.

A Collaborative Model for Improving Patient Engagement and Access for Hematopoietic Stem Cell Transplant and Clinical Gene Therapy Trials for Patients with Sickle Cell Disease in the Upper Midwest United States

Introduction: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy affecting populations across the United States. Several well-established patient-centered comprehensive care models have been in practice for preventive care and pain management. However, access to hematopoietic stem cell transplant (HSCT) and clinical trials for sickle cell gene therapies are limited, especially in pediatric and adult centers with limited HSCT-related resources. We describe a patient-centered collaborative model in the Upper Midwest United States to improve patient education and engagement as well as access to HSCT and gene therapy trials for patients with SCD. Collaborative Care Model: Since August 2021, centers across the Midwest meet monthly to improve access for HSCT and gene therapy as well as education about these therapies for individuals with SCD. The teams include: hematology and transplant teams from University of Minnesota, Comprehensive Sickle Cell Care team from Children's Hospital of Minneapolis, hematology and transplant team from Mayo Children's Hospital, hematology team from Essential Health, Duluth, Minnesota, hematology team from Sanford Children's Hospital Fargo and Sioux Falls and hematology team from Blank Children's Hospital, Des Moines, Iowa. This collaborative approach involves several stakeholders including an SCD community advocacy organization, hematology care providers across several rural as well as community/university hospitals, social workers, nurse coordinators, HSCT/gene therapy providers, as well as representatives from National Marrow Donor Program. Individual patient needs and available community support as well as institutional resources are discussed at length during monthly virtual meetings and a pre-intervention plan is established to ensure smooth transition of care to and from primary centers (Figure 1). Ongoing communication with the primary team helps with efficient transition of care after transplant as patients continue ongoing monitoring and care closer to home. Community partners help with early education of the families and provide necessary resources and support. Institutional partners like NMDP provide support with immune typing and discuss ongoing support and other resources available for providers and families. Results/Impact: Since the implementation of this collaborative model, there has been a steady increase in early referrals for education regarding HSCT and potential gene therapies trials for patients with SCD. There has been about 100% increase in new patient referrals since the implementation of this collaborative model compared to the average new referrals in the previous years (2021-22 vs 2018-19; Figure 2). Enrollment in HSCT as well as gene therapy clinical trials also has increased 2-3 folds since the implementation of the collaborative care model. It has helped established early discussion and longitudinal care and has also led to ongoing evaluation and discussions for availability of optimal donors, determining eligibility for HSCT and gene therapy trials as well as providing ongoing support and education to the sickle cell community and providers regarding the available therapies for SCD. This has also facilitated the transplant team establish earlier and better rapport with patients and their families and provide necessary education with an in-depth discussion regarding the potential benefits and risks of therapies such as HSCT and gene therapy. These discussions often occur over multiple visits and helps address psychological as well social barriers with a prospective evaluation. Additionally, the ongoing discussion among the providers helps with longitudinal monitoring of the patients and provide an assessment of the risks and benefits of therapies as the patient's disease course continues to evolve. This multi-stake holder collaborative approach continues to provide a well-established platform for discussion of newer therapies and access to open clinical trials, available resources for patients and families, and improve patient care and experience. The impact of this collaboration is noted in significant increase in early referrals and educational consults for HSCT and gene therapies, improved patient engagement as well as the acceptability and participation in clinical trials.

MAIT Cell Frequencies within PBSC Grafts Are Associated with Donor CMV Serostatus and Age: An Initial Analysis from the DKMS and NMDP Graft Composition Study

Introduction We have established an international collaboration between the DKMS (Germany) and the National Marrow Donor Program (NMDP; USA) to characterize more than 2000 donor peripheral blood stem cell (PBSC) grafts. We aim to correlate graft immunophenotype with patient outcomes and perform additional analyses on biobanked aliquots of selected samples to deepen our understanding of the relationships between features of the donor graft and key patient outcomes, such as graft-versus-host disease, relapse, and overall survival. Here, we present an interim analysis, focused on the CD8 T cell compartment, describing relationships between donor characteristics and graft composition. We have developed a novel computational clustering method to integrate cytometry data from both the US and German analytical laboratories. Methods 300 donor PBSC graft samples were collected, processed, freshly stained (34-color panel for immunophenotyping of lymphocytes and hematopoietic stem cells), and analyzed using an Aurora Cytek instrument at the NMDP contract laboratory (Roswell Park, Buffalo, NY). 53 additional samples were processed in the DKMS laboratory in Dresden, Germany (equivalent antibody panel and instrument). We have developed a novel analytical pipeline for integrating these data. First, we group samples by facility, and by month run for computational convenience, to form “batches” for initial clustering. We perform Leiden clustering, and subclustering, to generate a large number of clusters per batch. To integrate data from all batches, we then cluster all subcluster centroids from all batch-specific clusterings. This gives a global clustering for each stream ( e.g. the CD8+ T cells). Cluster frequencies per sample provide features for quantifying links between immunophenotype and donor metadata ( e.g., CMV serostatus, age, and sex). Our approach offers an important complement to traditional gating and allows full exploration of the data in an unbiased fashion. Results 353 donor products were included in the analysis. The median donor age was 28 years (range 18 - 60), 59% were female and 65% were CMV positive. Initial metaclustering demonstrated that the 53 DKMS samples and the 300 NMDP samples are each well represented in all clusters, and that site-driven batch effects, while present, are mild. We initially focused on the CD8 T cell compartment (UMAP in Fig 1A) and discovered several phenotypic differences when we compared CMV seronegative and seropositive donors. CD8 T cell clusters 10 and 11 (both TCRαβ+ CD45RA+ CCR7+ HLA-DR+ CD57+; cluster 10 CCR9+; cluster 11 CCR9-) were present at higher frequency in CMV+ donors (n = 116) compared with CMV- donors (n = 220; p <0.0001; Fig 1B). Conversely, clusters 9 and 12, enriched for mucosal-associated invariant T (MAIT) cells, were significantly reduced in CMV+ donors (p <0.001). Of note, CMV serostatus was not significantly associated with age (median age in the CMV+ group was 29.4 years; vs 28.4 years in CMV- donors). We also observed an association between cluster 8 (TCRαβ+ CD45RA+ CCR7+ HLA-DR+ CD38+; consistent with an activated phenotype) and age (p = 0.0009; Fig1B). There was a trend toward decreased MAIT frequencies with age (Cluster 9; p = 0.058). When we analyzed the MAIT cell frequency as defined by traditional flow cytometry gating (CD3+ CD8+ CD161+ Vα7.2+), we observed a statistically significant relationship between younger donor age and increased MAIT cell frequency (p = 0.0002), consistent with the trend seen in cluster 9. Sex at birth was not linked with immunophenotype in our analyses thus far. Conclusions In this initial analysis of our multi-center observational study of PBSC graft products, we demonstrate the development and application of new computational tools for large-cohort flow cytometric data analysis. CMV-positive serostatus and younger donor age are both associated with an increased frequency of MAIT cells in the graft. We also found differences in CD8 T cell activation status in association with age and CMV. In the future, we will assess the relationships between these populations and patient outcomes, as well as explore cluster frequencies in association with key patient outcomes including GVHD, relapse, and overall survival. Sample collection and analysis are ongoing at both US and German sites as an ongoing collaborative effort between the NMDP and the DKMS.

Factors Associated with Treatment Receipt in Medicare Beneficiaries Diagnosed with Acute Myeloid Leukemia

Background: The treatment a patient with AML receives may be influenced by where the patient is diagnosed and the physician making the initial diagnosis. Such factors could be targeted for intervention to help ensure patients receive optimal treatment; however, data constraints have previously limited a complete examination of patient, physician and hospital factors associated with treatment for AML. This study aimed to investigate the association of patient, hospital, and physician factors with treatment receipt for patients diagnosed with AML. Treatment receipt included allogeneic hematopoietic cell transplant (alloHCT) or chemotherapy without alloHCT among patients who received a National Marrow Donor Program (NMDP) donor search (search). Methods: Centers for Medicare and Medicaid (CMS) Medicare administrative claims data from 2010 to 2018 were linked to NMDP Donor Search data and to publicly available CMS and National Provider Identifier physician and hospital datasets. Patients aged 65-74 diagnosed with AML between 2010 and 2017 and enrolled in fee-for-service (Part A and B) Medicare for at least one year after diagnosis or until death, were included. The treatment groups (alloHCT and search) were identified using diagnosis and procedure codes. A multivariable hierarchical logistic regression procedure was performed to determine factors associated with treatment receipt, with hospital as a random effect. Models were adjusted for patient, hospital and physician characteristics identified at the time of diagnosis. Patients missing physician and hospital characteristics were excluded. Individuals with a racial/ethnic background of Black/African-American, Asian/Pacific Islander, Hispanic, American Indian/Alaska Native, and Other were grouped due to small numbers. All analyses were performed using Statistical Analysis Software (SAS ®) Enterprise Guide 7.1. Results: A total of 916 patients met eligibility criteria: 554 (60%) received alloHCT; 362 (40%) received search. The majority of patients in both groups were Non-Hispanic White and were age 65-69 years. A multivariable model demonstrated the variables associated with receipt of alloHCT (Figure 1). Characteristics significantly associated with decreased odds of receiving alloHCT were sex (male compared to female), race/ethnicity (a combined category of Black/African-American, Asian/Pacific Islander, Hispanic, American Indian/Alaska Native, and Other compared to Non-Hispanic White), living in an area with a lower percentage of population with a college education, age (71-75 compared to 65-69 years), and chemotherapy provision (chemotherapy not compared to provided by staff). Conclusion: This study used novel linked datasets to identify the association of patient, hospital, and physician characteristics at time of diagnosis with receipt of alloHCT, compared to patients who received a search but not an alloHCT. Notably, patient characteristics, and the hospital characteristic of provision of chemotherapy by hospital staff were associated with alloHCT receipt. Donor availability may contribute to the decreased odds of alloHCT by race/ethnicity, but studies to increase HLA-mismatched unrelated alloHCT are helping to decrease this barrier. Neighborhood education attainment was used as a proxy for socioeconomic status (SES), and SES has been associated with access to care. Ensuring treatment information is accessible and available in plain language may help patients considering different treatment options. Claims data is not collected for research, and has some inherent limitations, including the lack of disease severity, cytogenetics, patient preferences, and an algorithm was used to identify diagnosing physician and hospital. Additionally, this analysis includes patients who were able to access a transplant center to receive a search or alloHCT. Next steps will compare characteristics of those who received chemotherapy but did not receive a search to those who received a search and those who received an alloHCT. Study results will be used to help inform strategies aimed at improving access to treatment for patients diagnosed with AML.

Post-Transplant Cyclophosphamide Eliminates Disparity in GvHD-Free, Relapse-Free Survival and Overall Survival between 8/8 Matched and 7/8 Mismatched Unrelated Donor Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies

Background: Post-transplant cyclophosphamide (PTCy) has become a standard of care for graft-versus-host disease (GvHD) prophylaxis in recipients of human leukocyte antigen (HLA)-matched and mismatched unrelated donor (MMUD) allografts, generating new opportunities for successful hematopoietic cell transplantation (HCT) regardless of patient ancestry. The National Marrow Donor Program (NMDP)-sponsored 15-MMUD study, which used PTCy-based GvHD prophylaxis (PMID 3390526), demonstrated encouraging overall survival (OS) in adult patients receiving MMUD bone marrow grafts matched at ≤7/8 HLA alleles. Currently, the follow-up ACCESS study (NCT04904588) will determine if similar outcomes can be achieved using MMUD peripheral blood stem cell allografts. As part of its 5-year strategic plan, the NMDP aims to determine the extent of differences in GvHD-free, relapse-free survival (GRFS) between 8/8 and 7/8 URD allografts using PTCy and seeks to develop approaches over time to close the presumed gap in URD outcomes. Methods: The primary objective was to compare GRFS between 8/8 and 7/8 URD HCT using the Center for International Blood & Marrow Transplant Research (CIBMTR) database. After analyzing primary results, secondary objectives were added to compare GRFS, OS, and other clinical outcomes among 8/8 URD, 7/8 URD, and haploidentical-related donor (Haplo) HCT. The study included adult patients (age≥18y) with hematologic malignancies (ALL, AML, MDS) undergoing first URD or Haplo HCT between 2017-2020 using PTCy-based GvHD prophylaxis. Kaplan-Meier curves were used to estimate probability of GRFS and OS. Cox regression examined the independent effect of HLA match controlling for other clinical factors on outcomes referenced to 8/8 URD HCT. A priori clinically selected factors considered as possible confounders in the regression model included disease risk index, comorbidity risk, pre-HCT Karnofsky score, conditioning regimen intensity, graft source, donor/recipient CMV serostatus, year of HCT, donor/recipient age and race/ethnicity. Final models were stratified by factors violating the proportional hazards assumption. Factors were eliminated in a backwards fashion if p-values were >0.10 unless inclusion affected the hazard ratio (HR) of HLA match by more than 10%. Interactions were tested against a p-value of <0.01. Results: Table 1 shows demographics for the three patient cohorts: Haplo (n=2772), 8/8 URD (N=1517), and 7/8 MMUD (N=540). Notable differences among the cohorts included: 8/8 URD recipients had younger, predominantly Caucasian donors and were more likely to receive myeloablative conditioning. Haplo recipients had more donor/recipient CMV seropositivity and received more reduced intensity conditioning. Otherwise patient characteristics were similar. Contrary to our expectations, multivariable regression analysis (MVA) showed no significant differences in either GRFS or OS between recipients of 8/8 and 7/8 URD HCT at 1, 2 and 3-years post-HCT ( Figure 1). Outcomes, including relapse and NRM, between 8/8 and 7/8 URD HCT were similar irrespective of conditioning intensity. However, 8/8 URD HCT associated with lower two-year moderate/severe chronic GvHD than 7/8 URD [1.30 (1.00-1.68), p=0.049]. We next compared GRFS and OS among 8/8 and 7/8 URD and Haplo at 3y after HCT. On MVA, GRFS [HR 1.15 (1.04-1.26), p=0.005] and OS [HR 1.15 (1.03-1.29), p=0.013] were significantly better in 8/8 URD compared to Haplo HCT. Differences between 8/8 URD and Haplo appeared to be driven by significantly higher NRM [HR 1.46 (1.22-1.74), p<0.001)] and two-year moderate/severe chronic GvHD [HR 1.28 (1.07-1.54), p=0.007] in Haplo. No significant differences were seen in GRFS or OS at 3 years when comparing 7/8 URD to Haplo. Causes of death among donor types were similar with primary disease relapse/progression, infection and organ failure being the most frequent. Conclusions: Use of PTCy-based GvHD prophylaxis seems to have resolved previously observed differences in GRFS and OS between 8/8 and 7/8 URD HCT. HCT using an 8/8 URD HCT, if available, continues to be the best option for patients lacking a matched sibling donor. Further studies comparing Haplo to 7/8 URD HCT are warranted, but will require larger numbers of 7/8 URD HCT. Both mismatched donor sources substantially increase access to HCT for patients regardless of their ancestry.

Is the Youngest Donor Always the Best Choice to Optimize Outcomes for Matched Unrelated Allogeneic Transplant? Improving Precision Using Novel Statistical Methodology

INTRODUCTION Our recently published research has shown younger donors have superior survival for recipients of allogeneic hematopoietic stem cell transplant (HSCT). But, previously, we had not explored the donor age impact on other outcomes, or the impact of smaller age differences (<4 years) when balanced against other factors. We report results using our recently developed machine learning survival methodology, Nonparametric Failure Time Bayesian Additive Regression Trees (NFT BART). Here we study patient-specific optimization of donor selection for overall survival (OS) and event-free survival (EFS including events of death, relapse, graft failure/rejection, or moderate/severe chronic graft vs. host disease, GVHD). METHODS The patient data was provided by the Center for International Blood and Marrow Transplant Research. Each recipient underwent matched unrelated donor HSCT from 2016 to 2019 and was followed for OS and EFS outcomes up to three years. We trained our NFT BART model on 10,016 patients to provide predictions for OS and EFS. The model was validated on 1,802 patients among whom 699 had archived unrelated donor search records available from the National Marrow Donor Program. We examined donor age, sex/parity, CMV status, DPB1 nonpermissive mismatching, and DQB1 matching, while adjusting for relevant patient characteristics. We further restricted donor factors to those with a >1% positive impact on 3-year OS and/or EFS. Using archived search data for each patient, we examined three optimal strategies for donor selection: OS only, EFS only and a 2:1 weighted average between OS and EFS (denoted OS2:EFS1). The OS2:EFS1 effectively prioritizes optimizing OS while still allowing EFS consideration when the difference in OS predictions between two potential donors is minimal. We calculated predicted OS and EFS outcomes for each patient under all three optimal donor strategies. These predicted outcomes were benchmarked against observed practice by subtracting the predicted outcomes from the actual donor used for the transplant. RESULTS Among donor features, only age (for OS and EFS) and sex (for EFS) had clinically important impacts on outcomes. For OS, the youngest donor provided the best result regardless of patient characteristics: see the waterfall plot presented in Figure 1. As shown, the older the donor, the greater the impact of selection by age. Compared to donors 34+, use of an 18 year-old donor is associated with a substantial increase in OS where all of the recipient OS differentials are above 0.01. Compared to donors 22 to 30, the impact of an 18 year-old donor is negligible. For EFS, donor sex was the dominant factor, with males having a median 4% improvement in EFS at 3 years compared to females, while the difference for 42 vs. 18 was <2%. Optimizing for OS led to selection of the youngest donor regardless of sex, while optimizing EFS led to selection of the youngest male donor. Optimizing OS2:EFS1 generally picked the youngest donor except for selections of a male donor that may be older than the female when the age difference is small (median is 1 year older: Q1=0, Q3=2). In said cases, the OS detriment was minimal (median=-0.0005, Q1=-0.0008, Q3=-0.0003) with a substantial improvement in EFS (median=0.038, Q1=0.031, Q3=0.042) gained by switching to the male donor. Individual patient differences (OS2:EFS1 vs. actual donor) in OS vs. EFS are plotted in Figure 2. CONCLUSION Using our novel NFT BART methodology, we showed that donor selection to optimize HSCT outcomes can be improved by considering both OS and EFS. This weighted optimization strategy balances outcomes, prioritizing OS while also allowing for consideration of EFS when OS is likely similar between donors. Additionally, this supports previous research showing that choosing among donors from 18 to 30 with resultant minimal differences in outcomes that are negligible allowing for more flexibility in donor selection.

Improving Outcomes of Peripheral Blood Stem Cell (PBSC) HLA-Mismatched Unrelated Donor (MMUD) Hematopoietic Cell Transplantation (HCT): Effect of Graft Versus Host Disease (GVHD) Prophylaxis

Human leukocyte antigen (HLA) well matched donor (related or unrelated) has remained the preferred donor source for patients undergoing HCT for hematological disease, but the probability of finding a suitable related or unrelated donor has varied based on ethnic groups. HLA-mismatch unrelated donor (MMUD) transplantation has improved access to HCT in underrepresented minority groups and patients of mixed race. Historically, MMUD HCT has been associated with inferior survival outcomes compared to matched unrelated donor HCT when using conventional platforms of GVHD prophylaxis. (PMID: 31449184, 20538804). Efforts to improve outcomes have investigated the addition of a third agent such as anti-thymocyte globulin (ATG), mini-methotrexate (MTX) or mycophenolate mofetil (MMF). More recently, a study by the National Marrow Donor Program (NMDP) demonstrated the feasibility of post-transplant cyclophosphamide (PTCy) based GVHD prophylaxis in MMUD HCT using bone marrow (BM) grafts (PMID: 33905264). Additionally, our group demonstrated promising overall survival (OS) and GVHD-free/relapse-free-survival (GRFS) rates in peripheral blood stem cell (PBSC) MMUD HCT using PTCy based GVHD prophylaxis (PMID: 34156440). Here, we compare outcomes of PBSC MMUD HCT among patients receiving GVHD prophylaxis with either: (1) tacrolimus plus sirolimus (T/S), (2) T/S plus mini-methotrexate (T/S/MTX), or (3) PTCy, MMF, and tacrolimus or sirolimus (PTCy). Patients with various hematologic malignancies that underwent PBSC MMUD HCT (≥5/8 HLA-matched donors) at City of Hope between January 2005 and December 2021 were included in this retrospective review. Of 390 subjects included, GVHD prophylaxis included T/S (n=114), T/S/MTX (n=160), and PTCy (n=116). The median age was 51 (range:15-79), 53.3% of patients belonged to a racial/ethnic minority, and 34.8% (n=136) patients had disease risk index high or very high. Degree of HLA mismatch was 7/8 (91.3%), 6/8 (8.5%), and 5/8 (0.3%). Hematologic diseases included AML (40.3%), ALL (20.3%), MDS/MPN (15.9%), Lymphoma (16.9%), and CML/CMMol (6.7%). Most common conditioning regimens were fTBI-based (34.4%) and melphalan-based (57.2%). HCT comorbidity index was ≥ 3 in 30.8% (n=120), which was most common in PTCy compared to T/S and T/S/MTX: 48.3% vs. 23.7% vs. 23.1%, P<.001. The rate of neutrophil engraftment (15 days vs. 15 days vs 16 days, P=0.002) and platelet engraftment (15 days vs. 16 days vs 27 days, P=0.004) were shorter in T/S compared to T/S/MTX and PTCy, respectively. With median follow-up of 5.4 years (range: 1.0-16.7) the 5-year OS was superior in PTCy (P=0.045) compared to T/S and T/S/MTX: 58.0% (95% CI: 46.6-67.8) vs. 41.1% (95% CI: 31.9-50.1) and 39.6% (95% CI: 32-47.2). The 5-year disease-free survival (DFS) was superior in PTCy (P=0.042) compared to T/S and T/S/MTX: 54.2% (95% CI: 43.3-63.9) vs. 37.1% (95% CI: 28.2-46.0) vs. 37.2% (95% CI: 29.7-44.6), respectively. There was no significant difference in 5-year cumulative incidence of relapse (CIR) in T/S vs. T/S/MTX vs. T/S vs. PTCy: 29.1% (95% CI: 21.0-37.6) vs. 29.5% (95% CI: 22.6-36.7) vs. 22.1% (95% CI: 14.3-31.0), respectively. Additionally, there was no significant difference in 2-year NRM between the cohorts (P=0.459): 24.6% (95% CI: 17.1-32.9) vs. 23.1% (95% CI: 16.9-29.9) vs. 20.4% (95% CI: 13.5-28.4), respectively. The rate of 100-day Grade III-IV acute GVHD were similar between in the cohorts (P=0.321): 19.3% (95% CI: 12.6-27.0) vs. 18.1% (95% CI: 12.6 -24.5) vs. 12.9% (95% CI: 7.6-19.7). When comparing T/S vs. T/S/MTX and PTCy, the incidence of chronic GVHD was less in the PTCy cohort at both 1-year and 2-years (P<.001) with 1-year incidence of 55.0% (95% CI: 45.1-63.7) vs. 61.9% (95% CI: 53.8-68.9) vs. 38.9% (95% CI: 30-47.8), respectively, and 2-year incidence of 58.9% (95% CI: 49.0-67.6) vs. 66.2% (95% CI: 58.3-73.1) vs. 42.7% (95% CI: 33.4-51.6), respectively. To our knowledge, this is the largest reported single center outcome of PBSC MMUD HCT. In this study, we demonstrate the superiority of PTCy based GVHD prophylaxis compared to T/S and T/S/MTX in outcomes of 5-year OS (P=0.045), 5-year DFS (P=0.042), and incidence of chronic GVHD (P<.001). Our experience further supports the superiority of PTCy as the preferred GVHD prophylaxis in the PBSC MMUD HCT setting achieved by lowering chronic GVHD and associated complications.

CD33 CAR T-Cells (CD33CART) for Children and Young Adults with Relapsed/Refractory AML: Dose-Escalation Results from a Phase I/II Multicenter Trial

Introduction: Current therapies for patients with acute myeloid leukemia (AML) push the limits of chemotherapy intensity but cure only 30% of adults and 70% of children. Recently developed antibody-based therapies and molecularly-targeted agents only modestly improve outcomes for select patient subsets. Thus, new approaches are needed. Given the success of chimeric antigen receptor (CAR) T-cell therapies for acute lymphoblastic leukemia (ALL), we developed and optimized a novel CD33 CAR T-cell (CD33CART) construct for clinical testing in a multicenter Phase I/II clinical trial in children, adolescents, and young adults (AYA) with relapsed/refractory (r/r) AML. ( Qin H, et al. JITC 2021) We report interim results following completion of the dose-escalation phase. Methods: This multicenter phase I/II clinical trial (NCT03971799) was conducted as a 3+3 dose escalation study through the Pediatric Transplantation and Cell Therapy Consortium with National Marrow Donor Program sponsorship and managed by CIBMTR CRO. Autologous CD33CART product were centrally manufactured on a ClinicMACS Prodigy® by the Biopharmaceutical Development Program at the Frederick National Laboratory for Cancer Research (NCI). Eligibility criteria were r/r AML in subjects < 35 years old with adequate organ/performance status and an identified allogeneic stem cell transplant (SCT) donor. Bone marrow assessment was used for standard morphologic evaluation and central flow cytometric minimal residual disease (MRD) quantification. All subjects received pre-CD33CART lymphodepleting chemotherapy (LD) with fludarabine (75-120 mg/m 2) and cyclophosphamide (900-1000 mg/m 2). CD33CART doses levels (DLs) were: DL1: 3 x 10 5 CD33 CAR+ T-cells/kg; DL2: 1 x 10 6/kg; DL3: 3 x 10 6/kg and DL4: 1 x 10 7/kg. Adverse event grading used CTCAE v5 with incorporation of ASTCT consensus definitions for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Dose-limiting toxicities (DLTs) included > grade 3 CRS, > grade 3 ICANS, and persistent > grade 3 non-hematologic toxicity that did not resolve < grade 2 in 72 hours. CD33CART persistence was assessed via flow cytometric evaluation of the blood and bone marrow. Data cut-off was June 1, 2023. Results: A total of 24 subjects (median age of 16 years, range 1-34 years), were enrolled, 12 (50%) of whom underwent a prior SCT. CD33CART products were successfully manufactured for 23 subjects and infused into 19. In 4 non-infused subjects with manufactured products, 1 died from progressive disease (PD) prior to LD, 2 transitioned to palliative care and 1 withdrew consent to seek alternative therapy. Manufacturing was not performed in one subject due to death from PD after enrollment. One morbidly obese subject (BMI=49.3) enrolled at DL4 but received treatment at DL3 due to weight-based manufacturing limitations. The median time from enrollment to infusion was 47 days (range, 24-242). (Table) Three subjects each were infused at DL1 and DL2 without DLTs. At DL3, 1 subject experienced DLT (grade 4 CRS) prompting expansion at this dose level, and no subsequent DLTs were observed. At DL4, 1 subject experienced a prolonged grade 3 CRS (> 72 hours) and grade 3 ICANS, both constituting DLT and necessitating expansion of the cohort without additional DLTs seen. Across all dose-levels, CRS was seen in 13 (68%) patients and was > grade 3 in 4 (21%) with onset typically within the first 24 hours post-infusion. Complete remission (CR) was only seen at DL4 and achieved in 2 subjects, both achieving an MRD negative CR alongside myeloid aplasia. One SCT naïve subject developed candidemia during aplasia but was able to proceed to an allogenic SCT, achieved engraftment, and was in remission at Day +100 post SCT. The second patient (post-two prior SCTs) declined third SCT, had spontaneous count recovery and remained in remission until day +119 (MRD+ relapse). Transient CD33CART expansion was detected in 9 (47.4%) subjects overall and in all 6 (100%) subjects at DL4. Conclusions: CD33CART manufacturing is feasible in children and AYAs with r/r AML with acceptable toxicity experienced in treated subjects. CD33CART expansion was best in subjects treated at DL4 (1 x 10 7/kg) with MRD negative CRs and transient myeloid aplasia occurring in 2 of 5 (40%) subjects evaluable for response (Table). Based on early clinical efficacy at DL4, enrollment continues in the phase 2 portion.

Racial Disparity in Hematopoietic Stem Cell Transplant Clinical Trial Recruitment

Introduction: Race significantly influences phenotypic and genetic diversity in hematological diseases, consequently affecting disease prognosis, Human Leukocyte Antigen-matching and Hematopoietic Stem Cell Transplant (HSCT) outcomes. To ensure the development of novel transplant strategies effective for patients from diverse backgrounds, all racial groups must have equal opportunities to take part in HSCT clinical trials. Methods: Using ClinicalTrials.gov, a web-based resource that registers all studies meeting the definition of a clinical trial according to the International Committee on Medical Journal Editors, we identified all phase 1 to phase 4 HSCT clinical trials registered from 2006 to 2022. We manually abstracted data on the racial distribution of enrolled participants, sex distribution, transplant type, trial phase, location, and year of trial reporting. We calculated observed ratios of racial participation and compared them with the estimated probability of finding adequate donors from different racial subgroups reported by the National Marrow Donor Program to define the disproportionate enrolment factor. We then conducted subgroup racial distribution based on the trial phase, location, and type of transplant. We further evaluated trends in racial disparity within clinical trial enrolment over the years. Results: We identified 398 clinical trials related to HSCT between 2006 and 2022, of which 72% were allogenic and 28% were autologous HSCT trials. Most of these were phase 2 clinical trials (64.3%) and the majority (78.1%) were conducted in the United States. The racial distribution of enrolled participants was publicly available in 235 (59%) of these clinical trials, including 57.7% allogeneic and 62.5% autologous HSCT. The race distribution of enrolled subjects was reported in 80% of Phase 1 and 79% of Phase 3, whereas only 48% of Phase 1/2 and 44% of Phase 2/3 clinical trials reported racial distribution. The race distribution among 25,075 study participants in 235 clinical trials was: 80.4% Whites (20,175), 7.4% Blacks (1858), 5.3% Asians (1336), 1.6% other races (396), and 5.3% (1310) subjects with unreported race. The same race distribution trend was observed across all subgroups of clinical trials based on phase, location, and transplant type (Table 1). The disproportionate enrolment factor was 0.27 for Black participants, and 0.11 for Asian participants, compared to 1.02 for Whites. From 2006 to 2022, yearly trends for the absolute number of clinical trial enrollees showed a 2.5% and 1.5% increase in Black and Asian subject representation; however, minorities still accounted for only 20.3% of total representation in 2022 (Figure 1). Conclusions: Our results emphasize the significant racial underrepresentation of minority populations with a very low disproportionate enrolment factor in HSCT clinical trials despite the increased probability of finding a suitable donor resulting from novel HSCT technologies in recent years. Addressing these disparities requires urgent action and a multi-faceted approach. Efforts such as targeted outreach, cultural competence training and community engagement to focus on eliminating barriers are urgently needed to increase the enrolment of the minority population to achieve racial equity in HSCT.

Proceedings of the 2023 Second Annual ASTCT-NMDP ACCESS Initiative Workshop

Here the proceedings from the Second Annual American Society for Transplantation and Cellular Therapy (ASTCT) and National Marrow Donor Program (NMDP) ACCESS Initiative are reviewed to inform the hematopoietic cell transplantation (HCT) and cellular therapy (CT) ecosystem about progress and direction of the collaborative. Highlights from the meeting, including updates on the progress of projects from the Awareness, Poverty, and Racial Inequity Committees, are presented. The ACCESS Initiative continues to evolve and will remain dependent on the HCT/CT ecosystem's continued dedication to reduce barriers and improve outcome disparities for all patients in need of HCT/CT.

Abstract 15 A State-Run Public Cord Blood Collection Program

Abstract Introduction The Arizona Public Cord Blood Program was created in 2011 by the Arizona Biomedical Research Centre, a sub-section of the Arizona Department of Health Services, to advance the collection and increase the number of racially and ethnically diverse cord blood units available for transplantation, as well as promote awareness of the benefits of cord blood stem cells through our educational partner, Save the Cord Foundation (STCF). Objectives Create a sustainable program for women of all racial and ethnic backgrounds to have the opportunity to donate cord blood, with the primary goal of transplantation, and secondary goal of providing non-transplantable cord blood units for research. A second objective was to educate the residents of the state of Arizona about cord blood stem cells and the need for their preservation. Methods A portion of state lottery funds supports the program monetarily. Those funds are provided to four collection hospitals who employ "cord blood consenters" whose responsibility it is to consent patients, assist delivery providers with collections, and package and ship cord blood units to our partner cord blood bank at MD Anderson Cancer Center. There are also two clinical coordinators who educate and train hospital staff on quality collection practices, with special emphasis on the importance of high volume, sterile collections. STCF provides education across the state to expectant parents, healthcare providers, schools, and the public about the need for cord blood stem cell donation for transplant and research. Results Since 2011, the Arizona Public Cord Blood Program has banked hundreds of racially and ethnically diverse cord blood units with the National Marrow Donor Program, and has had 86 life-saving cord blood units matched with patients in need around the globe. This innovative program has not only expanded cord blood awareness and promoted the preservation of cord blood; it has resulted in the creation of an economic engine for the state of Arizona that is an attractant for STEM based businesses and careers. Discussion A decade later, the Arizona Public Cord Blood Program has proven to be a sustainable model for collecting and providing suitable cord blood units for transplant to diverse patient populations.

Cryopreservation of Growth Factor-Mobilized Peripheral Blood Stem Cells Does Not Compromise Major Outcomes after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

During the COVID-19 pandemic, cryopreservation of allogeneic donor stem cell products ensured availability of products at the start of conditioning for hematopoietic cell transplantation (HCT). Following recommendations from unrelated donor registries, including the National Marrow Donor Program (NMDP), many centers started to cryopreserve related donor peripheral blood stem cell (PBSC) products. Throughout the process, several centers have published outcomes with cryopreserved versus fresh products, some with conflicting results. Even though cryopreservation was initially considered only a temporary measure driven by the pandemic, potential advantages include greater flexibility of transplant timing. However, concern about detrimental effects of cryopreservation including increased risks of graft rejection, relapse and consequently mortality remained. The primary objective was to describe our center's experience comparing outcomes following PBSC transplantation with cryopreserved versus fresh grafts. This was an observational case study with retrospective review comparing cryopreserved grafts (N=213), to a recent historical cohort (controls) using fresh grafts (N=167). In multivariable analyses, the adjusted hazard ratio (fresh vs. cryo) we for overall mortality was HR= 1.20 (95% confidence interval (CI), 0.79-1.82; p=0.40), for non-relapse mortality HR=0.99 (95% CI, 0.55-1.77; p=0.98), and for relapse HR=0.94 (95% CI, 0.60 -1.48; p=0.80). The adjusted hazard ratio for platelet engraftment was HR=1.31 (95% CI, 1.05-1.63; p=.02) and the odds ratio of grades III-IV acute GVHD was OR=1.75 (95% CI 1.01-3.04; p=.05) with fresh compared to cryopreserved grafts. There was no demonstrable difference in the risk of chronic GHVD. Although longer-term follow-up is needed, these data provide preliminary reassurance that in the event of another pandemic or should the logistical need arise in individual patients, cryopreservation of PBSC products constitutes a reasonably safe alternative.

Existence of HLA-Mismatched Unrelated Donors Closes the Gap in Donor Availability Regardless of Recipient Ancestry

In patients without a matched sibling donor (MSD) or well-matched unrelated donor (MUD), hematopoietic cell transplantation (HCT) can still be successful when using an HLA-mismatched unrelated donor (MMUD) in combination with post-transplantation cyclophosphamide (PTCy), abatacept, or other novel approaches. This may allow clinicians to choose a suitable donor from a wide range of donor options while optimizing other donor selection characteristics, including donor age. We hypothesized that allowing for a 5/8 HLA match level considering high-resolution matching at HLA-A, -B, -C and -DRB1, there is a potential to close the donor availability gap for all patients regardless of their race/ethnicity. In this work, we estimate the likelihood of matching for all racial/ethnic groups at different HLA match thresholds. Our study aimed to assess the potential for identifying an available MUD or MMUD in the National Marrow Donor Program (NMDP)/Be The Match (BTM) donor registry for 21 detailed and 5 broad racial/ethnic groups, using high-resolution HLA matching for HLA-A, -B, -C, and -DRB1 at various levels (8/8, 7/8, 6/8, and 5/8). We used donor registry population data from the NMDP/BTM in 2020 and redistributed the donor registry data according to existing population ratios, accounting for demonstrated donor availability. Finally, we used a genetic model at the population level to estimate the match likelihood for detailed and broad racial/ethnic groups. Likelihood of 8/8 HLA match ranging from 16% to 74% were obtained for various detailed racial/ethnic groups with available donors age ≤35 years. When considering more mismatches in the HLA loci, registry coverage became >99% with a 5/8 HLA match level for donors of all ages or those age ≤35 years, with HLA-DPB1 T cell epitope permissive matching, or when searching for donors outside of their racial/ethnic group. Our registry models demonstrate the potential for using MMUDs at various HLA match levels to study whether this will expand access to HCT across racial/ethnic groups. Expanded donor options may erase the donor availability gap for all patients while allowing for selection of MMUDs with favorable characteristics, such as younger age.

Assessing Medicaid Coverage for Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy: A Project from the American Society for Transplantation and Cellular Therapy and the National Marrow Donor Program ACCESS Initiative

The American Society for Transplantation and Cellular Therapy (ASTCT) and the National Marrow Donor Program (NMDP) formed the ACCESS Initiative to address and reduce barriers to hematopoietic cell transplantation (HCT) and cellular therapy (CT) to ensure equal access and outcomes for all patients in need. The 3 committees, addressing awareness, poverty, and racial and ethnic inequity, defined pilot projects focusing on addressing relevant barriers to HCT/CT. Because many socioeconomically disadvantaged HCT/CT recipients receive care through state Medicaid programs, the Poverty Committee conducted a Medicaid scan of all 50 US states with the following objectives: to define beneficiary coverage for allogeneic and autologous HCT and chimeric antigen receptor (CAR) T cell therapy; to define support for travel, temporary lodging, and meals for both beneficiaries and caregivers; and to determine search and cell acquisition payment procedures. Here we summarize the results of the Medicaid scan and highlight significant variations and gaps in coverage for HCT/CT recipients. We also provide an initial roadmap for addressing gaps in Medicaid support for HCT and CAR-T therapy recipients.