Sanghee Hong

PURPOSE: Financial toxicity is common after bone marrow transplant (BMT) and is associated with worse quality of life, but longitudinal patterns remain poorly understood. METHODS: We conducted a prospective cohort study of insured adults undergoing allogeneic BMT (2018-2023). Financial toxicity (Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy) and quality of life (Functional Assessment of Cancer Therapy [FACT]–General, FACT-BMT) were assessed at baseline and at days (D) 90, 180, and 365. Longitudinal trends were analyzed using mixed-effects models. Relative risks (RR) for financial toxicity and hazard ratios (HR) for post-BMT mortality were estimated using generalized linear mixed-effects and time-varying Cox models. RESULTS: Among 214 transplanted patients, the median age was 58 years (IQR 46-66 year), 62% were male, and 80% were White; 47% had leukemia, 27% myelodysplastic syndrome, and 9% lymphoma; and 31% died by D365. At baseline, 56% reported none/minimal, 26% mild, and 18% moderate/high financial toxicity. Financial toxicity was associated with more cost-cutting behaviors, including reduced spending on food or clothing, use of savings, and prescription nonadherence. Expected probability of ≥mild financial toxicity reduced over time (39% baseline, 34% D90, 30% D180, 26% D365). Across time points, age >65 years and income >$90,000 in US dollars (USD) had 66% and 67% decreased risk of financial toxicity, respectively, compared with counterparts (n = 148, RR, 0.34, 95% CI [0.19 to 0.59]; RR, 0.33 [0.20 to 0.57]). Quality of life (n = 119 alive and with data by D365) with none/minimal or mild financial toxicity improved after transplant compared with baseline but significantly worsened for those with moderate/high financial toxicity over 1 year. Following adjustment for covariables, financial toxicity was not significantly associated with premature death after transplant (n = 214, HR, 1.10 [0.62-1.96]). CONCLUSION: Financial toxicity improved overtime with BMT, but persistent financial hardship was associated with quality of life. These findings support longitudinal screening and financial interventions across the transplant continuum.

Background: Patients with TP53 MUT MDS/AML experience poor clinical outcomes with high rates of disease recurrence and short overall survival (OS). Characterization of these individuals' post-HCT mortality is uniquely challenging due to competing risks from disease relapse and treatment toxicity. Transplant registries contain high-level outcomes data, however, there is a lack of detailed data in molecularly defined subsets of diease. This analysis was undertaken to bridge this gap. Methods: Allogeneic HCT recipients between 1/2014 and 12/2018 were retrospectively studied. Key inclusion criteria were TP53 MUT by NGS or deletion of chromosome 17/17p by FISH/cytogenetics. The primary outcome of non-relapse mortality (NRM) was defined as death from any cause other than disease with relapse as competing risk. Secondary outcomes for this analysis were OS, cumulative incidence of relapse (CIR), and relapse free survival (RFS). Relapse was defined as relapse/progression with NRM as competing risk. Results: 384 TP53 MUT MDS/AML patients were analyzed. 55% of patients were transplanted for AML, 41% received myeloablative conditioning (MAC), 39% had secondary MDS/AML, and 26% received prior chemo and/or radiation therapy (XRT). Median time from HCT to last follow-up was 321 days (range 8-2,385 days). Mutational data was available in 264 patients and cytogenetic data was available in 368 patients; 78% of patients had a complex karyotype (CK), 82% had TP53 missense mutations, and 74% had bi-allelic targeting of the TP53 gene. The incidence of all-grade acute and chronic GVHD (cGVHD) was 52% and 31%, respectively. One and 2 year OS was 48.5% and 30.9%, respectively. Estimated CIR at 1 and 2 years was 49% and 54.9%, respectively. The 1 year NRM was 13.7% and 2 year NRM was 18.1%. In multivariate analysis (MVA), there was no association between NRM and the clinical, molecular, or genetic features of TP53 MUT MDS/AML. HCT diagnosis of MDS (HR: 0.67, 95% CI: 0.46-0.97, p: 0.036), mono-allelic TP53 MUT (HR: 0.6, 95% CI: 0.39-0.94, p: 0.023), achievement of full donor PB chimerism (HR: 0.33, 95% CI: 0.14-0.85, p: 0.022), BM chimerism (HR: 0.33, 95% CI: 0.18-0.60, p: 0.003), and cGVHD (HR: 0.35, 95% CI: 0.23-0.51, p: <0.001) correlated with lower rates of relapse while CK predicted for increased relapse (HR: 2.5, 95% CI: 1.49-4.19, p: 0.001). Inferior OS was associated with CK (HR: 1.84, 95% CI: 1.19-2.85, p: 0.006) and history of prior chemo/XRT (HR: 1.84, 95% CI: 1.01-1.93, p: 0.006) whereas high KPS (HR: 0.98, 95% CI: 0.97-1, p: 0.046), mono-allelic TP53 mutations (HR: 0.52, HR: 0.36-0.77, p: 0.001), full donor PB chimerism (HR: 0.36, 95% CI: 0.19-0.68, p: 0.002), BM chimerism (HR: 0.3, 95% CI: 0.19-0.49, p: <0.001), and cGVHD (HR: 0.36, 95% CI: 0.18-0.36, p: <0.001) were associated with improved OS. In subgroup analysis, history of chemo and/or XRT increased NRM in AML (HR: 4.24, 95% CI: 1.35-13.39, p: 0.014). Pre-HCT TP53 MUT persistence by NGS (HR: 3.59, 95% CI: 1.43-9, p: 0.007) predicted for post-HCT relapse whereas pre-HCT CR (HR: 2.93, 95% CI: 1.54-5.59, p: 0.001) and full donor BM chimerism (HR: 0.14, 95% CI: 0.05-0.38, p: <0.001) were associated with lower rates of relapse. High KPS (HR: 0.96, 95% CI: 0.98-0.99, p: 0.021) and cGVHD (HR: 0.3, 95% CI: 0.16-0.56, p: <0.001) corresponded with improved OS. Prior chemo/XRT was associated with shorter OS (HR: 2.11, 95% CI: 1.06-4.18, p: 0.033) No significant NRM associations were identified in MDS. CK (HR: 5.04, 95% CI: 1.95-13.01, p: <0.001) and RIC/NMA conditioning intensity (HR: 2.54, 95% CI: 1.26-5.1, p: 0.009) increased risk of post-HCT relapse while full donor BM chimerism (HR: 0.15 95% CI: 0.08-0.31, p: <0.001), full donor PB chimerism (HR: 0.17, 95% CI: 0.17, p: <0.001), and cGVHD (HR: 0.17, 95% CI: 0.07-0.42, p:<0.001) reduced this risk. OS was improved with mono-allelic mutations (HR: 0.54, 95% CI: 0.32-0.96, p: 0.034), full donor BM (HR: 0.24, 95% CI: 0.12-0.71, p: <0.001), PB (HR: 0.29, 95% CI: 0.09-0.3, p: 0.007) chimerism, and cGVHD (HR: 0.16, 95% CI: 0.09-0.3, p: <0.001). Conclusions: From this large multi-institutional cohort of TP53 MUT myeloid neoplasms, we report a low NRM rate, likely due to high rates of post-HCT relapse/progression. These data demonstrate associations between bi-allelic TP53m/CK and post-HCT outcomes. Our work highlights the importance donor chimerism after HCT and provides new understanding of the importance of chronic GVHD in TP53 MUT MDS/AML. Figure 1 Figure 1. Disclosures: Byrne: Karyopharm: Research Funding. Logan: Amgen, Pfizer, AbbVie: Consultancy; Pharmacyclics, Astellas, Jazz, Kite, Kadmon, Autolus, Amphivena: Research Funding. Lee: CareDx: Membership on an entity's Board of Directors or advisory committees; Kadmon: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Fresensius Kabi: Consultancy; Jazz,: Consultancy; Incyte: Research Funding. Goodman: Seattle Genetics: Consultancy, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria. Gill: Interius Biotherapeutics: Current holder of stock options in a privately-held company, Research Funding; Novartis: Other: licensed intellectual property, Research Funding; Carisma Therapeutics: Current holder of stock options in a privately-held company, Research Funding. Jimenez: Takeda: Research Funding; AbbVie: Research Funding. Metheny: Pharmacosmos: Honoraria; Incyte: Speakers Bureau. Bhatnagar: Pfizer: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Cell Therapeutics: Honoraria, Research Funding; Kite: Honoraria; Karyopharm: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Research Funding. Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Mishra: Novartis: Research Funding. Savona:...

TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1–102 months) and 40 months (range: 1–106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2–4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2–4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2–4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2–4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Vitamin D plays an essential role in bone health, immune tolerance, and immune modulation. Autologous and allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk of vitamin D deficiency, which may increase risks of bone loss and fracture, graft-versus-host disease (GVHD), and relapse, and can delay hematologic and immune recovery following HCT. Growing evidence indicates that vitamin D may have a role as an immunomodulator, and supplementation during HCT may decrease the risk of GVHD, infection, relapse, and mortality. In this paper, we review the role of vitamin D and its association with HCT outcomes and discuss prevention and treatment of vitamin D deficiency after HCT in adult recipients. We review the role of monitoring of vitamin D levels pre- and post-HCT and its supplementation in appropriate patients. We also review the use of bone densitometry prior to HCT and in long-term follow-up and the treatment of osteoporosis in this high-risk population.