National Marrow Donor Program

Standardised data representation is fundamental to the integrity, interoperability and reproducibility of immunogenetics and histocompatibility testing. While well-established standards such as the genotype list (GL) String, histoimmunogenetics markup language (HML) and minimum information for reporting next-generation sequence genotyping exist for encoding HLA genotyping results, no equivalent syntax currently exists for describing phenotype- or antigen-level information that underlies antibody testing and immunological risk assessment. We introduce the phenotype list (PL) String grammar and the phenotype list string code (PLSC) syntax, structured, machine-readable grammars designed to represent antigen- and protein-level data across three contexts: (1) the HLA phenotype composition of assay reagents, (2) test results derived from those reagents and (3) clinical interpretations of HLA antibody specificities. PL String extends the hierarchical logic of the GL String grammar, while adapting a subset of GL String delimiters and rules to describe ambiguity, heterodimeric relationships and phenotypic composition. PL String incorporates explicit namespace definitions (e.g., World Health Organization HLA Nomenclature Committee for Factors of the HLA System, Organ Procurement and Transplantation Network, Eurotransplant and NMDP) to ensure traceability and compatibility with existing regulatory and operational frameworks. By harmonising how HLA phenotypic and antibody data are encoded, PL Strings enable automated data exchange between laboratories, registries and information systems, reducing transcription errors and improving computational interpretation. This new grammar establishes a foundation for interoperable representation of serologic and functional HLA data, facilitating reproducible research and enhancing clinical decision support in transplantation and immunogenetics. Technical specifications for PL Strings and PLSCs are available at plstring.org.

Background HLA-matched sibling donor (MSD) HCT is the standard upfront therapy for younger patients with SAA. For older patients or those lacking an MSD, immunosuppressive therapy (IST) has historically been preferred, with alternative donor HCT reserved for relapsed/refractory (r/r) disease. BMT CTN 1502 demonstrated encouraging outcomes using haploidentical (haplo) HCT (1-year overall survival 81% in r/r SAA). The ongoing BMT CTN 2207 (CureAA) trial is evaluating upfront alternative donor (unrelated and haplo) HCT. To inform dissemination and implementation (D&I) strategies for CureAA, the BMT CTN D&I committee, in collaboration with the Aplastic Anemia and Myelodysplastic Syndrome International Foundation (AAMDSIF) and the North American Pediatric Aplastic Anemia Consortium (NAPAAC) surveyed hematology and HCT physicians in the United States on practice patterns and barriers to HCT and CureAA enrollment. Methods An online survey was distributed to >3500 members of AAMDSIF, NAPAAC, and CIBMTR (June-July 2025). Eligible respondents were physicians who manage SAA. Questions assessed referral practices, donor preferences, trial awareness, and perceived barriers to enrollment. Results Of 135 responses, 116 were eligible (47% adult, 53% pediatric; 78% BMT physicians; 93% transplant-center based). 52% reported their practice consists of >20% minority patients; 31% reported >5% of their patients are uninsured. Most (66%) see 1–5 SAA patients annually; 25% see 5-9 and 9% see ≥10.HLA typing at diagnosis is nearly universal (adult 90%, pediatric 93%). Among adult providers, 20% start IST upfront, 35% evaluate or refer for HCT, and the remainder use age cut-offs for HCT referral (commonly <40 years). MSD status influences HCT referral for 7% of adult and 27% of pediatric providers. Barriers to HCT referral and donor type preferences are shown in Figures 1&2.Regarding trial awareness, 64% know of BMT CTN 1502; 86% are somewhat/very likely to offer haplo if no MSD is available in r/r SAA. Seventy percent are aware of CureAA, but only 40% are likely to refer for the trial; 32% reported lack of local trial access and 18% are unsure. Reported barriers to CureAA enrollment include competing trials and concerns about alternative donor use, long-term HCT effects, protocol design, and trial accessibility. Respondents are more or equally likely to refer based on the use of conditioning with 4 Gy total body irradiation (84%) and post-transplant cyclophosphamide (93%) in the study. Conclusions This national survey shows support for HCT in r/r SAA and openness for upfront alternative donor HCT within a trial. A key limitation of the study is the low participation from community physicians who treat SAA. Addressing concerns about accessibility, donor source, and long-term toxicity are critical to improving CureAA accrual and future adoption of alternative donor HCT.

Background ACCESS (NCT04904588), a multi-center phase II trial, was designed to assess safety and efficacy of HLA-mismatched unrelated donor (MMUD) peripheral blood allografts in adult patients with high-risk hematologic malignancies receiving myeloablative (MAC) or non-myeloablative/reduced-intensity conditioning (NMA/RIC) and standard-dose post-transplantation cyclophosphamide (SD PTCy) as graft-versus-host disease (GvHD) prophylaxis. One-year overall survival (75%) was similar irrespective of conditioning intensity and degree of donor HLA MM (Al Malki et al., JCO 2025). However, 56% MAC and 64% RIC adult recipients experienced at least one Common Terminology Criteria for Adverse Events (CTCAE) grade (Gr) ≥2 infection within the first 100 days of transplant (D100). Herein, we describe infection burden in ACCESS patients within one year after transplant. Methods CTCAE Gr≥2 infections were analyzed by time after transplant (Days 0-30, 31-100, 101-180, 181-365), conditioning intensity, degree of donor HLA MM (HLA 7/8 vs. <7/8), pathogen type, and post-MMUD HCT outcomes (Gr2-4 acute GvHD, moderate/severe chronic GvHD, and American Society for Transplantation and Cellular Therapy (ASTCT) Gr≥2 cytokine release syndrome. Infection density was calculated as number of infections per 100 days at risk for enrolled patients. Infection data were summarized with standard descriptive statistics. Infection density with 95% confidence intervals (CI) were estimated using Poisson regression models; p<0.05 was considered statistically significant. Results Median (range) ages for 268 patients receiving MAC (n=75) and RIC/NMA (n=193) were 49.8 (20.4-65.6) and 64.4 (24.3-77.9) years, respectively. CTCAE Gr≥2 infections occurred in 183 (69%) patients: 49 (65%) MAC and 134 (69%) RIC/NMA recipients. Days 0-30 infection densities for Gr2-5 and Gr3-5 infections were higher relative to infection densities at other post-transplant periods and irrespective of conditioning intensity (Fig. 1A) and degree of donor HLA MM (Fig. 1B). When comparing infection densities by conditioning intensity, patients receiving RIC/NMA had higher infection densities at Days 31-180 for Gr3-5 infections (Fig. 1A). When comparing infection densities by degree of donor HLA MM, significant differences were noted only at Days 181-365 in the RIC stratum (Fig. 1B). Similar distribution of pathogen types by conditioning intensity were noted early (Fig. 1C) and late (Fig. 1D) post-transplant, with predominantly gram-positive bacteria and non-respiratory viruses, respectively. Finally, pathogen type frequencies by clinical outcomes were indistinct (Fig. 1E). Conclusion In the MMUD PBSC transplant setting, SD PTCy associates with significant infection burden. These findings provide insights into potential interventions to prevent infection or augment immune response after MMUD transplant.

Introduction Allogeneic hematopoietic cell transplant (alloHCT) recipients have increased risk of developing subsequent neoplasms (SN). Cancer registry data provide detailed information on SN site, histology, and stage as well as systematic long-term ascertainment of new diagnoses. Objectives We therefore linked a cohort of 7820 recipients of alloHCT between 1991-2016 identified from the Center for International Blood and Marrow Transplant Research database to the population-based California Cancer Registry to increase the diagnostic specificity and long-term ascertainment of SNs with follow-up through 2018. Methods Standardized incidence ratios (SIRs) compared SN occurrence after alloHCT with the general population, and Poisson regression models compared SIRs across patient characteristics. Results Overall, 310 SNs were diagnosed, representing a 1.77-fold (95% confidence interval [CI]=1.59-1.98) higher rate than expected in the general population (Figure). SIRs were higher for squamous cell carcinomas (SCC) than non-SCC (SIR=5.55, 95%CI=4.44-6.95 versus SIR=1.46, 95%CI=1.28-1.66, P<0.0001). SCCs occurred most commonly in the oral cavity/pharynx (SIR=9.24, 95%CI=6.83-12.51), for which SIRs were highest for recipients of alloHCT before age 40 years (39.79, 95% CI=25.38-62.39) and persisted through >10 years of follow-up. SIRs were also elevated for SCCs of the gastrointestinal tract (SIR=6.56, 95%CI=3.72-11.54) and female genital tract (SIR=4.68, 95%CI 2.52-8.69). For other sites, overall SIRs were highest for thyroid cancer (SIR=4.60, 95%CI=3.06-6.92), bone and soft tissue sarcomas (SIR=4.43, 95%CI=2.89-6.80), brain/central nervous system cancers (SIR=3.11, 95%CI=1.96-4.94), and melanoma (SIR=3.10, 95%CI=2.39-4.03). Among these SN types, SIRs were highest for recipients of alloHCT before age 40 years for thyroid cancer (SIR=10.28), sarcomas (SIR=6.90), and brain/central nervous system cancers (SIR=10.18), but did not differ by age for melanoma. Elevated brain and central nervous system SIRs were restricted to >5 years after alloHCT (SIR=6.26), whereas risks did not differ significantly by time since alloHCT for thyroid cancer, sarcomas, and melanoma. The vast majority (86.2%) of alloHCT recipients diagnosed with breast cancer had in situ or localized disease. Breast cancer risk was not increased overall (SIR=0.92, 95%CI=0.64-1.33), but subgroup analyses showed significantly elevated SIRs for alloHCT recipients before age 40 years (SIR=2.51, 95%CI 1.48-4.23) and with long-term follow-up (>10 years: SIR=2.42, 95%CI=1.53-3.84). Conclusion These risk patterns for subsequent solid cancers after alloHCT emphasize the importance of long-term surveillance for this high-risk population.