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Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N=37,542; 37%) or autologous (N=...
Citations
... Given the complex and specialized nature of the modality, it is expected that allogeneic HCT outcomes could be affected by treating centers' experience. This concept, referred to as "the center effect," has been investigated; however, the results are conflicting [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. When interpreting the existing literature, it is worth noting that most of the previous studies analyzed heterogeneous patient populations with various diseases based on relatively older data. ...
... To date, several studies have investigated the center effect in allogeneic HCT; some have demonstrated the survival advantage for patients who undergo transplantation at high-volume centers [3-5, 8, 10-13, 15], whereas others have not [6,7,14]. Moreover, only a fraction of these studies have evaluated the center effect on relapse and NRM, with mixed results [3,4,8,10,11,15]. The major limitation in the existing literature is patient heterogeneity in terms of disease and healthcare environment. ...
... Because of the retrospective nature of the study, our results suffer from inherent biases, such as patient selection, treatment heterogeneity, and the presence of unmeasured factors. In addition, we used the number of allogeneic HCTs as an indicator of center experience, whereas several studies have shown that the prognostic relevance of other center factors, such as patient-per-physician ratio [7], accreditation status [9], and program duration [11], which were not taken into consideration in our study. While acknowledging these potential limitations, our analysis was strengthened by a homogeneous patient population, namely, adults with AML who underwent allogeneic HCT under a uniform healthcare system. ...
This study aimed to address the prognostic impact of center experience based on the data of 7821 adults with acute myeloid leukemia who underwent allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2019 in Japan, where medical care was provided within a uniform healthcare system. Center experience was defined based on the number of allogeneic HCTs performed for any indication during the study period, by which centers were divided into low-, intermediate-, and high-volume centers. After adjusting for known confounding factors, the risk of overall mortality was lowest for the high-volume centers and highest for the low-volume centers, with the difference between the center categories attributed primarily to the risk of relapse. Patients transplanted at high-volume centers had higher risks of acute and chronic graft-versus-host diseases but without an increased risk of non-relapse mortality (NRM). These findings reveal the presence of a center effect in allogeneic HCT conducted during the past decade in Japan, highlighting the difference in relapse based on center experience. The weaker effect on NRM compared with that on relapse suggests that the transplantation care quality is becoming equalized across the country.
... Thus, the analysis of HCT results in highly active transplantation centers remains an important benchmark for comparison. Despite several such benchmarks from developed countries [6,7], there are limited longitudinal data from centers in developing countries, while it is well known that economic healthcare background plays a role in HCT outcomes [8]. ...
Simple Summary
Despite several registry studies on the longitudinal outcomes of hematopoietic cell transplantation (HCT), there is limited information on the major trends in HCT in developing countries. This single-center study evaluates the development of a large transplantation center over 30 years. The analysis includes 5185 transplantations and focuses on major trends in indications over time and changes in outcomes according to the underlying disease. The most significant improvements of survival after autoHCT were observed in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4). The most significant improvements in survival after alloHCT were observed for acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia (HR 0.3, 95% CI 0.2–0.8).
Abstract
In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4–0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010–2014 vs. 38% in 2015–2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23–0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2–0.8).
... A life-threatening condition is a sudden, or predictable in the short term, severe clinical deterioration following serious damage to the body's functions requiring immediate treatment [4]. Emergencies occurring in the early post-transplant period, such as infections and complications related to the immune response, affect non-relapse mortality (NRM), estimated at 30% in allo-HSCT recipients and 13% after autologous transplant [5]. An early diagnosis of a life-threatening condition in patients undergoing HSCT, and the prompt implementation of the most effective therapy, can save the patient's life. ...
... Microeconomic and macroeconomic factors. Both centre-specific microeconomic data and country-specific macroeconomic factors were defined as previously described, and reflected status for the year 2016 [9]. Centre size was determined for each transplant by the number of transplants performed in this centre for the patient main disease in the year of the transplant (i.e. ...
We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980–2001 (cohort-1) and 2002–2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.
... JACIE has been increasingly recognised by governmental bodies and competent authorities in several EU member states and extends beyond Europe with accredited centres worldwide. Importantly, JACIE accreditation appears to have an impact on survival outcomes and donor safety [232,[338][339][340][341][342][343][344]. During the pandemic, JACIE supported self-assessment by centres to help maintain minimum quality standards in the midst of the challenges faced by health services. ...
For over two decades, the EBMT has updated recommendations on indications for haematopoietic cell transplantation (HCT) practice based on clinical and scientific developments in the field. This is the eighth special EBMT report on the indications for HCT for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on HCT indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered in conjunction with the risk of the disease, risk of HCT procedure and non-transplant strategies, including evolving cellular therapies. HCT techniques are constantly evolving and we make no specific recommendations, but encourage harmonisation of practice, where possible, to ensure experience across indications can be meaningfully aggregated via registry outputs. We also recommend working according to JACIE accreditation standards to maintain quality in clinical and laboratory components of practice, including benchmarking of survival outcomes. Since the last edition, the COVID-19 pandemic has affected clinical decision making and activity across indications. Although the full impact of the pandemic is yet to be determined, we recommend that decision making across indications is delivered with ongoing reference to EBMT and national COVID-19 guidance, in accordance with current local conditions.
... Therefore, developing additional cellular immune therapies to enrich a fragmented immune repertoire remains a major field of interest. However, as allo-HSCT is already a costly intervention and access to it is not equal for all European citizens [117], additional high-end prices will most likely not be accepted by many payers. To date, overpriced products, in combination with a long production time, have only been accepted for CAR T cells because of their nature as a single intervention for a cure with a big impact [118,119]. ...
In the complex interplay between inflammation and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-HSCT), viral reactivations are often observed and cause substantial morbidity and mortality. As toxicity after allo-HSCT within the context of viral reactivations is mainly driven by αβ T cells, we describe that by delaying αβ T cell reconstitution through defined transplantation techniques, we can harvest the full potential of early reconstituting γδ T cells to control viral reactivations. We summarize evidence of how the γδ T cell repertoire is shaped by CMV and EBV reactivations after allo-HSCT, and their potential role in controlling the most important, but not all, viral reactivations. As most γδ T cells recognize their targets in an MHC-independent manner, γδ T cells not only have the potential to control viral reactivations but also to impact the underlying hematological malignancies. We also highlight the recently re-discovered ability to recognize classical HLA-molecules through a γδ T cell receptor, which also surprisingly do not associate with GVHD. Finally, we discuss the therapeutic potential of γδ T cells and their receptors within and outside the context of allo-HSCT, as well as the opportunities and challenges for developers and for payers.
... Few studies have examined the association of transplant center characteristics with survival after HCT [12][13][14][15][16]. A 1992 study from the Center for International Blood and Marrow Transplant Research (CIBMTR), an international HCT clinical outcomes registry, showed higher risk of treatment failure in centers that transplanted fewer than six patients annually [12]. ...
... A follow-up study in 2001 that used survey information from the United States (US) transplant centers and their patient outcomes data showed that clinical severity of patients and physician case load was associated with 1-year mortality [13]. Retrospective studies from Europe have also suggested an association between center volume and alloHCT survival [14,15]. We conducted a study to examine the association of center characteristics with alloHCT outcomes in a period during which substantive changes in indications and practice and advances in transplantation techniques and supportive care have occurred [1, 17,18]. ...
... We designed our study to address this limitation of existing research in the context of alloHCT. Similar to prior studies [12][13][14]37], we identified center volume as a significant predictor for survival. However, we were not able to identify specific center structural factors and care delivery models besides the availability of a survivorship program that may explain this association. ...
Allogeneic hematopoietic cell transplantation (alloHCT) is a highly specialized procedure. We surveyed adult transplant centers in the United States (US) and then used data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008–2010) to evaluate associations of center volume, infrastructure, and care delivery models with survival post alloHCT. Based on their 2010 alloHCT volume, centers were categorized as low-volume (≤40 alloHCTs; N = 42 centers, 1900 recipients) or high-volume (>40 alloHCTs; N = 41 centers, 9637 recipients). 100-day survival was 86% (95% CI, 85–87%) in high-volume compared with 83% (95% CI, 81–85%) in low-volume centers (difference 3%; P < 0.001). One-year survival was 62% (95% CI, 61–63%) and 56% (95% CI, 54–58%), respectively (difference 6%; P < 0.001). Logistic regression analyses adjusted for patient and center characteristics; alloHCT at high-volume centers (odds ratio [OR] 1.32; P < 0.001) and presence of a survivorship program dedicated to HCT recipients (OR 1.23; P = 0.009) were associated with favorable 1-year survival compared to low-volume centers. Similar findings were observed in a CIBMTR validation cohort (2012–2014); high-volume centers had better 1-year survival (OR 1.24, P < 0.001). Among US adult transplant centers, alloHCT at high-volume centers and at centers with survivorship programs is associated with higher 1-year survival.
... Recent medical advances have made allogeneic hematopoietic cell transplantation (allo-HCT) more accessible to a constantly increasing number of patients that can now benefit from this procedure, [1][2][3] but with a significant burden of infectious complications. 2 As complete immune reconstitution may not occur until up to 1-2 years post-allo-HCT, 3 management of infection is critical in these patients. ...
... Recent medical advances have made allogeneic hematopoietic cell transplantation (allo-HCT) more accessible to a constantly increasing number of patients that can now benefit from this procedure, [1][2][3] but with a significant burden of infectious complications. 2 As complete immune reconstitution may not occur until up to 1-2 years post-allo-HCT, 3 management of infection is critical in these patients. ...
Background
Infections are an important complication after allogeneic hematopoietic cell transplantation (allo‐HCT). The present study aimed at determining the landscape of infections occurring in a large cohort of allo‐HCT patients, as well as associated risk factors for infections and for one‐year non‐relapse mortality.
Methods
This is a retrospective cohort study using STCS and EBMT databases to assess the one‐year incidence rate of infection, as well as risk factors for infections and for one‐year non‐relapse mortality among adult allo‐HCT patients transplanted between 2010 and 2014 in Switzerland. Univariable and multivariable quasi Poisson and multivariable Cox regression models were used.
Results
Of 553 patients included, 486 had an infection with a global incidence rate of 3.66 infections per patient‐year. Among a total of 1534 infections analyzed, viral infections were predominant (n=1138, 74.2%), followed by bacterial (n=343, 22.4%) and fungal (n=53, 3.5%) infections. At one year, the cumulative incidence of relapse and non‐relapse mortality were 26% and 16%, respectively. 195 (35.3%) of patients had at least one episode of severe graft‐versus‐host‐disease (GvHD). A center effect was observed, and underlying disease, donor type, cytomegalovirus serological constellation and GvHD were also associated with the incidence rate of infections. There was an increased risk for one‐year non‐relapse mortality associated with all pathogens, specifically within two months of infection, and this remained true beyond 2 months of a fungal infection.
Conclusion
Despite advances to limit infections in this population, they still occur in most allo‐HCT patients with a major impact on survival at one year.
... Centre specific microeconomic and country specific macroeconomic factors were integrated as previously described [18]. Centre size was defined for each transplant by the number of transplants performed in the centre for the main disease of the patient in the year of the transplant (0-4, 5-19, 20+ transplants). ...
Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55′668 deaths in 114′491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980–2001) to cohort 2 (2002–2015) in all post-transplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country- related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of “unknown origin”.
... Importantly, however, whilst we will plan to incorporate additional clinical variables to fine tune The scientific potential of benchmarking also needs to be developed from a health economic perspective. Firstly, it is fair to recognise that some countries in the EBMT community do not have the same resources as others, acknowledging that macroeconomic factors have been shown to have an impact on HSCT outcomes [29]. This will be even more relevant as centres in low-income and middleincome countries (LMIC) engage with FACT and JACIE initiatives [30]. ...
... For long-term sustainability, there is a need for evidence of sufficient impact on patient outcomes to justify the considerable time and resources invested. This is an 'improvement science' issue, similar to the exercises performed to demonstrate the potential benefits of implementation of JACIE accreditation [14,15,29]. ...
In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.
