27 research outputs found
Incidence, Risk Factors, and Outcomes of Early Adverse Cardiac Events (EACE) after Allogeneic Hematopoietic Stem Cell Transplantation Stratified by Conditioning Regimen
Voriconazole Exposure and the Risk of Cutaneous Squamous Cell Carcinoma in Allogeneic Hematopoietic Stem Cell Transplant Patients
A systematic review of religious beliefs about major end-of-life issues in the five major world religions
Differential Expression of Interferon-Induced Genes and Other Tissue-Based Acute Gvhd Biomarkers in Acute Gvhd Compared to Lupus Erythematosus in Skin
Calcium metabolism of intact and thyroparathyroidectomized rats fed a bicarbonate enriched diet
Cardiovascular outcomes in patients receiving myeloablative vs. reduced intensity conditioning prior to allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
Age is no barrier for adults undergoing HCT for AML in CR1:contemporary CIBMTR analysis
Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1,321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007–2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60–64; 65–69; 70+). With median follow-up of nearly 3 years, patients aged 60–64 had modestly, though significantly better OS, DFS and lower TRM than those either 65–69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p=0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥ 3. Conditioning intensity was not a significant predictor of OS in the 60–69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p=0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection
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Pre-MEASURE: Multicenter evaluation of the prognostic significance of measurable residual disease testing prior to allogeneic transplantation for adult patients with AML in first remission
7006 Background: Measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplantation (alloHCT) is associated with increased relapse and death in patients with acute myeloid leukemia (AML) in cytomorphological complete remission (CR). We recently demonstrated AML MRD detected in pre-alloHCT blood by DNA-sequencing was associated with increased relapse and decreased overall survival in patients randomized to reduced intensity conditioning (RIC) versus myeloablative conditioning (MAC). The clinical utility of such ultra-deep next-generation sequencing (NGS-MRD) had not yet been reported in a large multi-center cohort. Methods: Patients aged 18 or older who underwent first alloHCT between 2013-2017 for AML in first CR (CR1), reported to be FLT3, NPM1, IDH1, IDH2 and/or Kit mutated at diagnosis, with a pre-conditioning remission blood sample available in the CIBMTR biobank were eligible for this study. Ultra-deep anchored multiplex PCR-based NGS-MRD for the above mutations was performed on 500ng gDNA with error-corrected variant calling as previously described. The pre-specified statistical analysis plan was registered on OSF. Results: Of 457 patients with a sample available, 448 had sufficient clinical annotation and DNA for analysis. 147 of these 448 patients (33%) experienced relapse at a median of 5.6 months post-alloHCT. NGS-MRD was positive in 129 pre-alloHCT patient samples (29%), averaging 1.35 mutation(s)/patient (range: 1-4). 173 mutations were detected with a median VAF of 0.18% (range: 0.0054-62%), most frequently FLT3-ITD (n = 43 patients), NPM1 (n = 48), and IDH2 (n = 46). Testing positive by NGS-MRD prior to alloHCT was associated with a 3yr RFS of 36% (95% CI: 28-45%) compared with 56% (51-62%) in those testing negative (p < 0.001). Detection of NPM1 and/or FLT3-ITD mutations prior to alloHCT was associated with a 3yr relapse probability of 55% (43-67%) and RFS of 26% (16-37%). NGS-MRD impact was modified by conditioning intensity: positive patients receiving RIC/NMA had the highest relapse of 57% at 3yr, testing negative followed by RIC/NMA had the same relapse rate at 3yr (35%) as those who tested positive but received MAC (p < 0.001). At three years, those positive for FLT3-ITD and/or NPM1 mutations prior to RIC/NMA alloHCT had a relapse probability of 67% (50-83%) with a RFS of 19% (8-33%). HR for relapse if NGS-MRD positive pre-alloHCT in CR1 was 2.3 (p < 0.001, 95% CI 1.6-3.1) when adjusting for conditioning intensity and age group. Conclusions: In this largest cohort of NGS-MRD testing prior to alloHCT for AML reported to date, we confirm the ability to identify patients in CR1 but at high-risk of subsequent relapse. This evidence provides the foundation for future precision medicine approaches to reduce post-transplant AML relapse