Dataset Information

Analysis of disparities in time to allogeneic transplantation in adults with acute myelogenous leukemia.

ABSTRACT: Although alternative donors extend transplant access, whether recipient ancestry affects the time to allogeneic transplant is not established. We analyzed the likelihood of clinically significant delays to allograft by patient ancestry in 313 adult patients with acute myelogenous leukemia (AML) who underwent transplantation. Non-European ancestry patients (n = 99) were more likely than Europeans (n = 214) to receive HLA-mismatched donor allografts (45% vs 24%). Overall, the median time from transplant indication to allograft was 127 days (range, 57-1683). In multivariable analysis, non-Europeans had an increased risk of prolonged indication to transplant time >180 days owing to significant delays in indication to consult >90 days and consult to transplant >120 days. Compared with recipients of HLA-matched unrelated donors (URDs), HLA-mismatched adult donor recipients were at an increased risk of delayed indication to transplant, whereas HLA-identical sibling and cord blood recipients were at a lower risk. Subanalysis showed more indication to transplant delays >180 days in non-European (44%) vs European (19%) 8/8 URD recipients. Finally, the pandemic further exacerbated delays for non-Europeans. In summary, although non-European patients with AML are less likely to receive 8/8 URDs as expected, if they do, their transplants are delayed. HLA-identical siblings and cord blood facilitate the fastest transplants regardless of patient ancestry, whereas other adult donor transplants are delayed. Strategies to mitigate referral barriers, hasten donor evaluation, and use all alternative donor sources are critical to ensure timely transplantation for patients with AML.

SUBMITTER: Fingrut WB

PROVIDER: S-EPMC10393759 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Analysis of disparities in time to allogeneic transplantation in adults with acute myelogenous leukemia.

Fingrut Warren B WB Gyurkocza Boglarka B Flynn Jessica J Davis Eric E Devlin Sean S Scaradavou Andromachi A Chinapen Stephanie S Quach Sean S Cho Christina C Giralt Sergio A SA Jakubowski Ann A AA Lin Richard J RJ Papadopoulos Esperanza B EB Perales Miguel-Angel MA Ponce Doris D Shaffer Brian C BC Tamari Roni R Young James W JW Politikos Ioannis I Barker Juliet N JN

Blood advances 20230801 15

Although alternative donors extend transplant access, whether recipient ancestry affects the time to allogeneic transplant is not established. We analyzed the likelihood of clinically significant delays to allograft by patient ancestry in 313 adult patients with acute myelogenous leukemia (AML) who underwent transplantation. Non-European ancestry patients (n = 99) were more likely than Europeans (n = 214) to receive HLA-mismatched donor allografts (45% vs 24%). Overall, the median time from tran ...[more]

PMID: 36240477

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Project description:Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with t-AML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT.

Project description:Decitabine is a hypomethylating agent that irreversibly inhibits DNA methyltransferase I, inducing leukemic differentiation and re-expression of epigenetically silenced putative tumor antigens. We assessed safety and efficacy of decitabine maintenance after allogeneic transplantation for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Decitabine maintenance may help eradicate minimal residual disease, decrease the incidence of graft-versus-host disease (GVHD), and facilitate a graft-versus-leukemia effect by enhancing the effect of T regulatory lymphocytes. Patients with AML/MDS in complete remission (CR) after allotransplantation started decitabine between day +50 and +100. We investigated 4 decitabine doses in cohorts of 4 patients: 5, 7.5, 10, and 15 mg/m(2)/day × 5 days every 6 weeks, for a maximum 8 cycles. The maximum tolerated dose (MTD) was defined as the maximum dose at which ≤ 25% of people experience dose-limiting toxicities during the first cycle of treatment. Twenty-four patients were enrolled and 22 were evaluable. All 4 dose levels were completed and no MTD was reached. Overall, decitabine maintenance was well tolerated. Grade 3 and 4 hematological toxicities were experienced by 75% of patients, including all patients treated at the highest dose level. Nine patients completed all 8 cycles and 8 of them remain in CR. Nine patients died from relapse (n = 4), infectious complications (n = 3), and GVHD (n = 2). Most occurrences of acute GVHD were mild and resolved without interruption of treatment; 1 patient died of acute gut GVHD. Decitabine maintenance did not clearly impact the rate of chronic GVHD. Although there was a trend of increased FOXP3 expression, results were not statistically significant. In conclusion, decitabine maintenance is associated with acceptable toxicities when given in the post-allotransplantation setting. Although the MTD was not reached, the dose of 10 mg/m(2) for 5 days every 6 weeks appeared to be the optimal dose rather than 15 mg/m(2), where most hematological toxicities occurred.

Project description:Allogeneic hematopoietic cell transplantation (alloHCT) is a resource-intensive procedure and the sole potentially curative treatment available for patients with acute myelogenous leukemia (AML). Although Medicare coverage may help address a major financial barrier to accessing alloHCT, there remains an unmet need for alloHCT owing to sociodemographic disparities. This study examined trends and factors associated with the utilization of alloHCT and the estimated unmet need for alloHCT among Medicare beneficiaries with AML. This retrospective cohort study included patients (age 65 to 74 years) with a diagnosis of AML identified in Medicare claims data from 2010 through 2016. To study trends in utilization, transplantation rates were calculated as the number of patients who underwent alloHCT within 180 days and 1 year of diagnosis (numerator) divided by the total number of patients with AML within each diagnosis year (denominator). A multivariable logistic regression was used to identify factors associated with the likelihood of undergoing alloHCT within 1 year of diagnosis. Two approaches were applied to estimate the unmet need for alloHCT. The first approach used claims data to identify the potential need for alloHCT among patients who achieved complete remission for at least 90 days. The second approach used established National Marrow Donor Program (NMDP) methodology, which considers estimates of risk level, response to treatment, comorbidity, and early mortality, to identify the potential and unmet need for alloHCT. The overall estimated need and unmet need from 2010 to 2015 and over different time periods were evaluated for both approaches. The alloHCT rate within 180 days of diagnosis increased from 8% in 2010 to 15.8% in 2016 (P < .001), and the 1-year alloHCT rate also increased over time, from 11.9% in 2010 to 20.0% in 2015 (P < .001). The likelihood of undergoing alloHCT within 1 year of diagnosis was associated with diagnosis year, age, race, geographic region, Elixhauser Comorbidity Index, and population-level median household income. Between 2010 and 2015, the claims data approach estimated a lower potential need for alloHCT compared with the NMDP methodology estimate (27% versus 36%); both approaches estimated that 43% to 44% of patients with a potential need for alloHCT had an unmet treatment need. Despite the differences in estimated potential need between the 2 approaches, both showed a sustained unmet need but with a downward trend over time. Our data show that utilization of alloHCT has increased over time among Medicare beneficiaries with AML. Two approaches of need analysis were conducted for validation of estimated need and unmet need for alloHCT using claim-identified remission status, given the lack of cytogenetics and molecular information in claims data. Both approaches to estimating the unmet need for alloHCT found a downward trend over time; however, there are differences in utilization of alloHCT by age, race, geographic region, comorbidity, and socioeconomic status, indicating disparities in access to alloHCT among Medicare beneficiaries with AML. This suggests the need for policy efforts, research, and continued education to improve access to alloHCT and to close the gap between the actual utilization of alloHCT and the unmet need.

Project description:The adverse prognosis of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3-ITD) in patients with acute myelogenous leukemia (AML) may depend on allelic burden. We compared postremission treatment with chemotherapy and hematopoietic stem cell transplantation (HSCT) in 169 FLT3-ITDmut intermediate cytogenetic risk AML patients with allelic ratio evaluable at diagnosis who achieved first complete remission (CR1) with induction therapy. To minimize selection bias, the analysis was limited to patients who remained in CR1 for at least 4 months (median time to HSCT) after achieving CR1, and propensity score matching was implemented. Sensitivity analysis including patients who remained in CR1 for at least 3 months was applied as well. HSCT in CR1 was associated with longer relapse-free survival (RFS) and overall survival (OS), with 3-year estimated rates of 18% and 24%, respectively (P < .001), for patients receiving chemotherapy and 46% and 54%, respectively (P < .001), for those undergoing HSCT. Multivariate regression models showed that HSCT remained statistically significant with improved RFS and OS independent of FLT3-ITD allelic ratio and NPM1 status. Irrespective of postremission therapy, relapse remains the main reason for treatment failure, with a 3-year incidence of 68% in chemotherapy recipients versus 41% in HSCT recipients. Allogeneic HSCT improved disease outcomes compared with chemotherapy after propensity score matching was applied. The improvement observed for RFS (hazard ratio [HR], 0.55; P = .09) and OS (HR, 0.58; P = .10) with HSCT as postremission therapy in patients who remained in CR1 for at least 4 months did not reach statistical significance; however, the sensitivity analyses including patients who remained in CR1 for at least 3 months showed significant improvement in both RFS (HR, 0.31; P = .002) and OS (HR, 0.27; P = .02) after propensity score matching. Our results indicate that HSCT in CR1 for AML FLT3-ITDmut patients is associated with longer RFS and OS. Innovative transplantation strategies to improve relapse incidence are urgently needed.

Project description:Patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) generally have poor overall survival (OS). Interventions that result in improved OS after relapse are not well established. The efficacy of second cellular therapy and specific indications are matters of debate. This study was conducted to evaluate factors associated with postrelapse survival and the efficacy of a second course of cellular therapy. We retrospectively analyzed consecutive patients with AML and MDS who underwent a first allo-HCT between 2010 and 2017 at our center but subsequently relapsed. One hundred and four patients with AML and 44 patients with MDS were included (total n = 148). Bone marrow (BM) and peripheral blood stem cell grafts were either unmodified or T cell-depleted (TCD) by CD34+ selection ex vivo. Forty-five patients (30.4%) received a second cellular therapy after relapse, either a second allo-HCT (n = 28; 18.9%) or donor leukocyte infusion (DLI) (n = 17; 11.5%). The median age at transplantation was 60 years (range, 24 to 78 years). The median time to relapse (TTR) after transplantation was 6.5 months (range, 1 to 60.9 months), and the ensuing median OS was 6 months (95% confidence interval [CI], 4.8 to 8.9 months). In univariable analysis, longer TTR, relapse type (measurable residual disease versus morphologic), relapse occurring in the most recent years, and receipt of cellular therapy after relapse were associated with better outcomes, whereas adverse cytogenetics and/or abnormality of TP53, as well as NPM1 mutation in patients with AML, were associated with adverse outcomes. Relapse type, year of relapse, and a variable resulting from the combination of TTR and receipt of second cellular therapy remained significantly associated with postrelapse survival in multivariable analysis. In a separate multivariable model, adjusted only for TTR, relapse type, and receipt of second cellular therapy, an adverse effect of NPM1 mutation on survival was confirmed. We could not show an effect of post-transplantation maintenance on survival after relapse. In both univariable and multivariable analysis, we found a positive association for second cellular therapy with survival after relapse in patients who relapsed early (<6 months) after allo-HCT and a similar trend in patients who relapsed late (>12 months) after transplantation. Two-year OS after a second cellular therapy was 44.9% (95% CI, 28.5% to 61.4%), and it was significantly better in patients with <5% BM blasts before cell infusion. We could not show different effects on survival after second cellular therapy for DLI versus second allo-HCT in univariable analysis. Survival after relapse is improving over time, but this remains a challenging event, especially for patients who relapse early after transplantation. We found that a second cellular therapy could offer a benefit even in these cases. Nonetheless, more research is needed to clarify the most appropriate treatment choices after relapse. These are probably driven by underlying genetic and immunologic conditions, which should be the focus of future studies.

Dataset Information

Analysis of disparities in time to allogeneic transplantation in adults with acute myelogenous leukemia.

Publications

Analysis of disparities in time to allogeneic transplantation in adults with acute myelogenous leukemia.

Similar Datasets

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