The Evolution of Hematopoietic Stem Cell Transplantation to Overcome Access Disparities: The Role of NMDP.

NMDP recognizes that despite advances in hematopoietic stem cell transplantation (HSCT) and other cell therapies, not all patients have equitable access to treatment, and disparities in outcomes remain. This paper explores the recent work of NMDP to accelerate progress and expand access to more patients through transformative clinical research, particularly in the use of mismatched unrelated donors for HSCT.

Current trends and outcomes in cellular therapy activity in the United States, including prospective Patient Reported Outcomes data collection within the CIBMTR registry.

BACKGROUND: Center for International Blood and Marrow Transplant Research (CIBMTR) prepares an annual set of summary slides to detail the trends in transplantation and cellular therapies. For the first time in the 2023 summary slides, CIBMTR incorporates data for patients receiving chimeric antigen receptor T-cell (CAR-T) infusions. In addition, the data on patient-reported outcomes (PROs) is also included. OBJECTIVES: This report aims to update the annual trends in US HCT activity and incorporate data on the use of CAR-T therapies. Here we also aim to present and describe the development, implementation, and current status of the PRO data collection. STUDY DESIGN: In August 2020, CIBMTR launched the Protocol for Collection of Patient Reported Outcomes Data (CIBMTR PRO Protocol). The CIBMTR PRO Protocol operates under a centralized infrastructure to reduce burden to centers. Specifically, PRO data is collected from a prospective convenience sample of adult HCT and CAR-T patients who received treatment at contributing centers and consented for research. Data are merged and stored with the clinical data and used under the governance of the CIBMTR Research Database Protocol. Participants answer a series of surveys developed by the Patient Reported Outcomes Measurement Information System© (PROMIS) focusing on physical, social and emotional, and others measures assessing financial well-being, occupational functioning, and social determinants of health. To complement traditionally measured clinical outcomes, the surveys are administered at the same timepoints that clinical data is routinely collected. RESULTS: As of September 2023, PRO data from 993 patients across 25 different centers has been collected. With the goal of incorporating these important patient perspectives into standard clinical care, CIBMTR has added the PRO data to Data Back to Centers (DBtC). Through expanding the data types represented in the registry, CIBMTR aims to support holistic research accounting for the patient perspective in improving patient outcomes. CONCLUSION: PRO data at CIBMTR aims to provide the foundation for future large scale, population-level evaluations to determine areas for improvement, emerging disparities in access and health outcomes (eg, by age, race, and ethnicity), and new therapies that may impact current treatment guidelines. Continuing to collect and grow the PRO data is critical for understanding these changes and identifying methods for improving patient quality of life.

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

Optimal Donor Selection Across Multiple Outcomes For Hematopoietic Stem Cell Transplantation By Bayesian Nonparametric Machine Learning.

Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative treatment options for patients suffering from life-threatening hematologic malignancies; yet, the possible adverse complications can be serious even fatal. Matching between donor and recipient for 4 of the HLA genes is widely accepted and supported by the literature. However, among 8/8 allele matched unrelated donors, there is less agreement among centers and transplant physicians about how to prioritize donor characteristics like additional HLA loci (DPB1 and DQB1), donor sex/parity, CMV status, and age to optimize transplant outcomes. This leads to varying donor selection practice from patient to patient or via center protocols. Furthermore, different donor characteristics may impact different post transplant outcomes beyond mortality, including disease relapse, graft failure/rejection, and chronic graft-versus-host disease (components of event-free survival, EFS). We develop a general methodology to identify optimal treatment decisions by considering the trade-offs on multiple outcomes modeled using Bayesian nonparametric machine learning. We apply the proposed approach to the problem of donor selection to optimize overall survival and event-free survival, using a large outcomes registry of HCT recipients and their actual and potential donors from the Center for International Blood and Marrow Transplant Research (CIBMTR). Our approach leads to a donor selection strategy that favors the youngest male donor, except when there is a female donor that is substantially younger.

Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance.

Data on recent bone marrow harvest (BMH) collections from the NMDP has shown that bone marrow (BM) quality has decreased based on total nucleated cell count in the product. To ensure that quality BM products are available to all recipients, the NMDP Marrow Alliance was formed in April 2021 to increase the capability of BM collection centers to safely deliver high-quality products consistently and to identify and disseminate guidelines for performing BMH. This white paper describes the best practices for BMH as defined by the NMDP Marrow Alliance.

Long-term Outcomes of Peripheral Blood Stem Cell Unrelated Donors Mobilized with Filgrastim.

Allogeneic hematopoietic cell transplantation is a life-saving procedure used to treat of a variety of devastating diseases. It requires hematopoietic stem cells collected via filgrastim mobilized peripheral blood stem cells or bone marrow harvest from volunteer unrelated donors. There is a paucity of safety data regarding donors' long-term adverse events. This prospective, observational study combined peripheral blood stem cell donors enrolled on the NMDP Investigational New Drug trial and bone marrow donors between July 1, 1999, and September 30, 2015. The primary objective was to describe the long-term incidence of myeloid malignancies. Secondary objectives included describing the long-term incidence of lymphoid malignancies, non-hematologic malignancies, autoimmune disorders, and thrombotic events. 21643 donors (14530 peripheral blood stem cells and 7123 bone marrow) were included. The incidence rate of myeloid disorders per 100000 person years in donors of peripheral blood stem cells was 2.53 (95% CI: 0.82-7.84) and in donors of bone marrow it was 4.13 (95% CI: 1.33-12.8). The incidence rate ratio of peripheral blood stem cells /bone marrow donors was 0.61 (95% CI: 0.12-3.03; p=0.55). The incidence of other malignancies, autoimmunity, and thrombosis did not differ between donor types. This comprehensive study of long-term effects of filgrastim in unrelated donors of peripheral blood stem cells provides strong evidence that donors who receive filgrastim are not at increased risk of these events compared to bone marrow donors. It also provides reassurance to current donors undergoing stem cell mobilization as well as individuals considering joining stem cell registries such as NMDP.

Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3.

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

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

ABSTRACT: The 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.

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.

Measurable Residual IDH1 before Allogeneic Transplant for Acute Myeloid Leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk.

Reducing barriers of access and care related to hematopoietic cell transplantation and cellular therapy: The mission-driven role of the national marrow donor program.

The treatment of malignant and nonmalignant hematologic disorders continues to benefit from significant scientific advancement and progress in the use of hematopoietic cell transplantation and cellular therapies. However, barriers associated with receiving these lifesaving treatments and care remain, which necessitate innovative approaches to overcome, so all persons in need can receive these therapies. This article reviews barriers to receiving hematopoietic cell transplantation and cellular therapies, and highlights novel approaches taken by the National Marrow Donor Program in reducing barriers for all patients in need.

Clinical impact of cryopreservation of allogeneic hematopoietic cell grafts during the onset of the COVID-19 pandemic.

At the onset of the COVID-19 pandemic, the National Marrow Donor Program mandated the cryopreservation of hematopoietic cell grafts from volunteer unrelated donors because of numerous patient and donor safety concerns and logistical hurdles. Using the Center for International Blood and Marrow Transplant Research outcomes database, we report the impact of cryopreservation on overall survival (OS) and other outcomes within 1 year after hematopoietic cell transplantation (HCT). We analyzed 1543 recipients of cryopreserved allografts receiving HCT at US centers during the first 6 months of the pandemic and compared them with 2499 recipients of fresh allografts during a 6-month period in 2019. On multivariable regression analysis, we observed no difference in the OS (P = .09), nonrelapse mortality (P = .89), graft-versus-host disease (GVHD), or GVHD- and relapse-free survival (P = .58) in recipients of cryopreserved vs fresh allografts. Disease-free survival (DFS) was lower in the cryopreserved allograft recipients (P = .006) because of a higher risk of relapse (P = .01) compared with the fresh allograft recipients. Primary graft failure was higher (P = .01), and the risk of chronic GVHD was lower (P = .001) with cryopreservation compared with fresh grafts. In conclusion, although there was no negative impact of cryopreservation on OS, relapse was higher, and DFS was lower than that with no cryopreservation. Fresh grafts are recommended as the pandemic-related logistical hurdles resolve. Cryopreservation should be considered an option for patients when fresh grafts are not feasible.

Real-World Data Showing Trends and Outcomes by Race and Ethnicity in Allogeneic Hematopoietic Cell Transplantation: A Report from the Center for International Blood and Marrow Transplant Research.

The use of HLA-mismatched donors could enable more patients with ethnically diverse backgrounds to receive allogeneic hematopoietic cell transplantation (HCT) in the United States. However, real-world trends and outcomes following mismatched donor HCT for diverse patients remain largely undefined. We conducted this study to determine whether the use of mismatched donor platforms have increased the access to allogeneic HCT for ethnically diverse patients, particularly through the application of novel graft-versus-host disease (GVHD) prophylaxis regimens, and whether outcomes for diverse patients are comparable to those of non-Hispanic White patients. This observational cross-sectional study used real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. All patients receiving their first allogeneic HCT in the United States between 2009 and 2020 were included, with a focus on transplantations performed in 2020. Data from patients undergoing allogeneic HCT using bone marrow, peripheral blood, or cord blood from HLA-matched or mismatched related and unrelated donors were analyzed. Specifically, relative proportion of allogeneic HCT was generated as percentage of total for donor type and for patient age, disease indication, GVHD prophylaxis, and race and ethnicity. Causes of death were summarized using frequencies, and the Kaplan-Meier estimator was used for estimating overall survival. Compared to matched related donor and matched unrelated donor HCT, more ethnically diverse patients received mismatched unrelated donor, haploidentical donor, and cord blood HCT. Although matched unrelated donor remains the most common donor type, the use of haploidentical donors has increased significantly over the last 5 years. Paralleling this increase in haploidentical HCT is the increased use of post-transplantation cyclophosphamide (PTCy) as GVHD prophylaxis. Relative to previous transplantation eras, the most contemporary era is associated with the highest survival rates following allogeneic HCT irrespective of patient race and ethnicity. Nonetheless, disease relapse remains the primary cause of death for both adult and pediatric allogeneic HCT recipients by donor type and across all patient racial/ethnic groups. Ethnically diverse patients are undergoing allogeneic HCT at higher rates, largely through the use of alternative donor platforms incorporating PTCy. Maintaining access to potential life-saving allogeneic HCT using alternative donors and novel GVHD prophylaxis strategies and improving HCT outcomes, particularly disease relapse, remain urgent clinical needs.

DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.

Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized. Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants. Design, Setting, and Participants: In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research. Exposure: Centralized DNA sequencing of banked pretransplant remission blood samples. Main Outcomes and Measures: The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models. Results: Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P < .001) and decreased survival at 3 years (39% vs 63%; difference, -24% [2-sided 95% CI, -39% to -9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P < .001). Conclusions and Relevance: Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia.

Wearable sensor-based performance status assessment in cancer: A pilot multicenter study from the Alliance for Clinical Trials in Oncology (A19_Pilot2).

Clinical performance status is designed to be a measure of overall health, reflecting a patient's physiological reserve and ability to tolerate various forms of therapy. Currently, it is measured by a combination of subjective clinician assessment and patient-reported exercise tolerance in the context of daily living activities. In this study, we assess the feasibility of combining objective data sources and patient-generated health data (PGHD) to improve the accuracy of performance status assessment during routine cancer care. Patients undergoing routine chemotherapy for solid tumors, routine chemotherapy for hematologic malignancies, or hematopoietic stem cell transplant (HCT) at one of four sites in a cancer clinical trials cooperative group were consented to a six-week prospective observational clinical trial (NCT02786628). Baseline data acquisition included cardiopulmonary exercise testing (CPET) and a six-minute walk test (6MWT). Weekly PGHD included patient-reported physical function and symptom burden. Continuous data capture included use of a Fitbit Charge HR (sensor). Baseline CPET and 6MWT could only be obtained in 68% of study patients, suggesting low feasibility during routine cancer treatment. In contrast, 84% of patients had usable fitness tracker data, 93% completed baseline patient-reported surveys, and overall, 73% of patients had overlapping sensor and survey data that could be used for modeling. A linear model with repeated measures was constructed to predict the patient-reported physical function. Sensor-derived daily activity, sensor-derived median heart rate, and patient-reported symptom burden emerged as strong predictors of physical function (marginal R2 0.429-0.433, conditional R2 0.816-0.822). Trial Registration: Clinicaltrials.gov Id NCT02786628.

Three-Year Outcomes in Recipients of Mismatched Unrelated Bone Marrow Donor Transplants Using Post-Transplantation Cyclophosphamide: Follow-Up from a National Marrow Donor Program-Sponsored Prospective Clinical Trial.

The use of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has resulted in reductions in GVHD and improved outcomes in allogeneic hematopoietic cell transplantation (HCT) using HLA-mismatched related donors. We report the 3-year outcomes of the first multicenter prospective clinical trial using PTCy in the setting of mismatched unrelated donor (MMUD) bone marrow HCT. The study enrolled 80 patients, treated with either myeloablative conditioning (MAC; n = 40) or reduced-intensity conditioning (RIC; n = 40), with the primary endpoint of 1-year overall survival (OS). The median follow-up for this study was 34 months (range, 12 to 46 months) in the RIC group and 36 months (range, 18 to 49 months) in the MAC group. Three-year OS and nonrelapse mortality were 70% and 15%, respectively, in the RIC group and 62% and 10% in the MAC group. No GVHD was reported after 1 year. The incidence of relapse was 29% in the RIC group and 51% in the MAC group. OS did not differ based on HLA match grade (63% in the 7/8 strata and 71% in the 4 to 6/8 strata). These encouraging outcomes, which were sustained for 3 years post-HCT, support the continued exploration of MMUD HCT using a PTCy platform. Important future areas to address include relapse reduction and furthering our understanding of optimal donor selection based on HLA and non-HLA factors.

Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors. Methods: NMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal-Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused. Results: Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor. Conclusion: Throughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe.

Updated Trends in Hematopoietic Cell Transplantation in the United States with an Additional Focus on Adolescent and Young Adult Transplantation Activity and Outcomes.

Hematopoietic cell transplantation (HCT) has been successfully used to treat many malignant and nonmalignant conditions. As supportive care, donor selection, and treatment modalities evolve, documenting HCT trends and outcomes is critical. This report from the Center for International Blood and Marrow Transplant Research (CIBMTR) provides an update on current transplantation activity and survival rates in the United States. Additional data on the use and outcomes of HCT in the adolescent and young adult (AYA) population are included. AYA patients more frequently receive peripheral blood stem cell grafts than pediatric patients, which may reflect differences in practice in pediatric versus adult treatment centers. The proportions of donor types also differ those in adult and pediatric populations. Outcomes for patients in the AYA age range are similar to those of pediatric patients for acute myelogenous leukemia but worse for acute lymphoblastic leukemia. Outcomes for both leukemias are better in AYA patients compared with older adults. Comparing the time periods 2000 to 2009 and 2010 to 2019 revealed significant improvement in overall survival across the age spectrum, but the greatest improvement in the AYA age group.