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- Farhadfar, Nosha, et al.
(författare)
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Impact of Pretransplantation Renal Dysfunction on Outcomes after Allogeneic Hematopoietic Cell Transplantation
- 2021
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:5, s. 410-422
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Tidskriftsartikel (refereegranskat)abstract
- Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age >= 40 years who under went alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age <40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR >= 90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR <45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR <60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR >= 90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR <45 mL/min group. Compared with the eGFR >= 90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P < .0001) and the eGFR <45 mL/min group (HR, 3.09; P < .0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR <45 mL/min was associated with an increased overall mortality (HR, 1.63; P < .0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.
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| 2. |
- Narayan, Rupa, et al.
(författare)
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HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia
- 2023
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Ingår i: Transplantation and cellular therapy. - : Elsevier BV. - 2666-6367. ; 29:7, s. 1-452
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Tidskriftsartikel (refereegranskat)abstract
- Mutation-bearing peptide ligands from mutated nucleophosmin-1 (NPM1) protein have been empirically found to be presented by HLA class I in acute myeloid leukemia (AML). We hypothesized that HLA genotype may impact allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes in NPM1-mutated AML owing to differences in antigen presentation. We evaluated the effect of the variable of predicted strong binding to mutated NPM1 peptides using HLA class I genotypes from matched donor-recipient pairs on transplant recipients’ overall survival (OS) and disease-free survival (DFS) as part of the primary objectives and cumulative incidence of relapse and nonrelapse mortality (NRM) as part of secondary objectives. Baseline and outcome data reported to the Center for International Blood and Marrow Transplant Research from a study cohort of adult patients (n = 1020) with NPM1-mutated de novo AML in first (71%) or second (29%) complete remission undergoing 8/8 matched related (18%) or matched unrelated (82%) allo-HCT were analyzed retrospectively. Class I alleles from donor-recipient pairs were analyzed for predicted strong HLA binding to mutated NPM1 using netMHCpan 4.0. A total of 429 (42%) donor-recipient pairs were classified as having predicted strong-binding HLA alleles (SBHAs) to mutated NPM1. In multivariable analyses adjusting for clinical covariates, the presence of predicted SBHAs was associated with a lower risk of relapse (hazard ratio [HR],.72; 95% confidence interval [CI],.55 to.94; P =.015). OS (HR,.81; 95% CI,.67 to.98; P =.028) and DFS (HR,.84; 95% CI,.69 to 1.01; P =.070) showed a suggestion of better outcomes if predicted SBHAs were present but did not meet the prespecified P value of <.025. NRM did not differ (HR, 1.04; P =.740). These hypothesis-generating data support further exploration of HLA genotype-neoantigen interactions in the allo-HCT context.
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