异基因移植的共病筛选标准

We previously reported that the Charlson Comorbidity Index (CCI) was useful for predicting outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). However, the sample size of patients with scores of 1 or more, captured by the CCI, did not exceed 35%. Further, some comorbidities were rarely found among patients who underwent HCT. Therefore, the current study was designed to (1) better define previously identified comorbidities using pretransplant laboratory data, (2) investigate additional HCT-related comorbidities, and (3) establish comorbidity scores that were suited for HCT. Data were collected from 1055 patients, and then randomly divided into training and validation sets. Weights were assigned to individual comorbidities according to their prognostic significance in Cox proportional hazard models. The new index was then validated. The new index proved to be more sensitive than the CCI since it captured 62% of patients with scores more than 0 compared with 12%, respectively. Further, the new index showed better survival prediction than the CCI (likelihood ratio of 23.7 versus 7.1 and c statistics of 0.661 versus 0.561, respectively, P < .001). In conclusion, the new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival. This index will be useful for clinical trials and patient counseling before HCT.

Key Points Cardiac, pulmonary, hepatic, and renal dysfunction were predictive of allo-HCT mortality and combined to form the SCI. The new index stratified patients into distinct NRM risk groups and was valid in 2 cohorts.

The development of tools for the prediction of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (HSCT) would offer a major guidance in the therapeutic decision. Recently, the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) has been associated with increased NRM risk in several retrospective studies, but its clinical utility has never been demonstrated prospectively in an adequately sized cohort. To this aim, we prospectively evaluated a consecutive cohort of 1937 patients receiving HSCT in Italy over 2 years. HCT-CI was strongly correlated with both 2-year NRM (14.7%, 21.3%, and 27.3% in patients having an HCT-CI score of 0, 1-2, and ≥ 3, respectively) and overall survival (56.4%, 54.5%, and 41.3%, respectively). There was an excellent calibration between the predicted and observed 2-year NRM in patients having an HCT-CI score of 0 and 1-2, whereas in the ≥ 3 group the predicted NRM overestimated the observed NRM (41% vs 27.3%). HCT-CI alone was the strongest predictor of NRM in patients with lymphoma, myelodysplastic syndrome, and acute myeloid leukemia in first remission (c-statistics 0.66, 064, and 0.59, respectively). We confirm the clinical utility of the HCT-CI score that could also identify patients at low NRM risk possibly benefiting from an HSCT-based treatment strategy.

Comorbidity measurements have recently been used to improve estimation of tolerance to allogeneic hematopoietic cell transplantation (HCT). We sought to determine the independent effect of comorbidity and performance status on HCT outcome and to devise a simple risk classification system for transplant-related mortality. We analyzed 105 consecutively enrolled patients who underwent HCT and received reduced intensity conditioning with fludarabine, melphalan, and alemtuzumab. Comorbid conditions were tabulated using 2 scales, the Charlson Comorbidity Index (CCI) and the Kaplan-Feinstein Scale (KFS). Comorbid conditions were found in 47% of patients by the KFS and in 27% by the CCI (P < .001). Using the Eastern Cooperative Oncology Group Performance Status (PS) scale, 34% had a PS score >0 (range, 0-2). A simple scale combining the KFS and PS enabled separation of high- from low-risk patients, with 6-month cumulative incidences 50% and 15%, respectively for transplant-related mortality (P = .001) and enhanced prognostic power over the CCI alone (P = .018). Prospective studies evaluating more comprehensive functional and comorbidity measurements are warranted.

… increasingly offered allogeneic nonmyeloablative hematopoietic cell transplantation (HCT). … Herein, a recently developed HCT‐specific comorbidity index (HCT‐CI) was compared with …

The hematopoietic cell transplantation-comorbidity index (HCT-CI) is a comorbidity tool suited for recipients of HCT. The index has been shown to sensitively capture the prevalence and magnitude of severity of various organ impairments before HCT and to provide valuable prognostic information after HCT. Many investigators have validated the discriminative power of the HCT-CI, but others have not. One concern is the consistency in comorbidity coding across different evaluators, particularly in view of the relatively recent addition of the HCT-CI to the transplant evaluation process. In this article, comorbidity scoring was tested across different evaluators, and only a fair interobserver agreement rate could be detected. To address these issues, a brief training program is proposed here, consisting of systematic methodology for data acquisition and consistent guidelines for comorbidity coding that were summarized in a Web-based calculator. In a validation patient cohort, this training program was shown to improve the interevaluator agreement on HCT-CI scores to an excellent rate with weighted κ values in the range of 0.89 to 0.97. This proposed training program will facilitate reliable assessment of comorbidities in the clinic and for research studies leading to standardization of the use of comorbidities in prediction of HCT outcomes.

In the context of allogeneic hematopoietic cell transplantation (allo-HSCT), comorbidities are an important risk factor. Use of the hematopoietic cell transplantation-specific comorbidity index (HSCT-CI), which was developed and validated in Seattle, Washington, has been proposed to predict the probability of nonrelapse mortality (NRM) and overall survival (OS) following allo-HSCT. We performed a single-center retrospective study to validate the prognostic impact of HSCT-CI on transplant outcomes in a cohort of high-risk acute myeloid leukemia patients undergoing allo-HSCT between January 2000 and December 2008. The median patient age at the time of transplantation was 53 years (range: 11-76 years). The median pretransplantation HSCT-CI score was 4 (range: 0-10). Among 340 patients, OS at 3 years was 29% (95% confidence interval [CI]: 17%-41%), 40% (33%-47%), and 44% (41%-47%) in the low-, intermediate-, and high-risk HSCT-CI groups (P = .7), respectively. The corresponding NRM at 3 years was 34% (10%-58%), 32% (20%-44%), and 26% (20%-32%; P = .6). In multivariate analysis, we found no predictive value of HSCT-CI for either OS or NRM. The use of HSCT-CI as a decision-making tool for transplantation eligibility should not be considered until its validity has been unequivocally shown in crossvalidation studies.

ABSTRACT Introduction: Allogeneic hematopoietic cell transplantation (HCT) provides potential cure to a large number of malignant and nonmalignant hematological disorders. With the development of non-myeloablative and reduced-intensity conditioning regimens, allogeneic HCT can nowadays be offered to a number of older or medically unfit patients. Up until the twenty-first century, chronological age was considered a hypothetical barrier. Recent reports, however, have shown that comorbidities, function, and other patient-related factors influence HCT outcomes at a higher magnitude than age alone. Areas covered: To define the eligibility of older or medically unfit patients for allogeneic HCT, a range of factors have to be considered. To solve this considerable issue, we need to further understand the mechanism and consequences of aging, such as chronic inflammation, sarcopenia, and especially the structure of frailty. Domains covering functional, physical, mental, social, nutritional, bone, and other health statuses should be evaluated and considered. Expert commentary: In this review we merge the current assessment tools with the potential approaches to objectify functional resources, as well as with possible methods to improve these resources in older or otherwise medically unfit patients prior to allogeneic HCT.

Identifying which patients are at high risk for transplant related mortality, prior to allogeneic hematopoietic cell transplantation (alloHCT) is crucial both to guide decision-making with patients and families and to inform the alloHCT approach. There is a paucity of data evaluating the utility of the HCT comorbidity index (HCT-CI) in pediatric patients. We performed a retrospective cohort study of 188 patients who underwent alloHCT between January 2008 and October 2016 and assessed pre-transplant comorbidities defined and weighted by the HCT-CI. The primary endpoint of our study was overall survival (OS). Kaplan-Meier method was used to assess survival estimates at one-year post-transplant and did not differ based on HCT-CI scores: 78.7% (SE 6.69%) for HCT-CI=0, 74.7% (SE 6.33%) for HCT-CI=1-2, 77.3% (SE 4.17%) for HCT-CI ≥3. Multivariable Cox proportional hazards analysis did not show HCT-CI having an effect on OS: hazard ratio (HR) 0.633 (95% Confidence Interval [CI] 0.297-1.347) for HCT-CI scores 1-2, HR 0.935, (95%CI CI 0.456-1.918) for HCT-CI scores ≥3, compared to scores of 0. The most frequent comorbidities observed were hepatic disease (mild in 29%, severe in 23%) and pulmonary disease (moderate in 15% and severe in 29%). However, only 55% were able to complete pulmonary function testing (PFT). Hepatic disease was based on transaminitis in 48% and by bilirubin alone in 26% of patients; 46% of patients with hepatic dysfunction had an underlying hemoglobinopathy and hyperbilirubinemia related to ongoing hemolysis. This study evaluates HCT-CI comorbidities in greater detail than has been performed previously in children undergoing alloHCT. We identify challenges with the HCT-CI in the pediatric population and highlight the comorbidities that may benefit from adjustments to their definition to create an improved risk assessment tool for children.

For most acute myeloid leukemia (AML) patients an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of cure. The introduction of less toxic non-myeloablative conditioning (NMA) regimes enabled older and/or comorbid patients to be consolidated with an allogeneic HSCT. While the hematopoietic cell transplantation comorbidity index (HCT-CI) predicted outcomes in many younger patient cohorts its impact in older AML patients receiving NMA-HSCT remains unknown. Here we analyzed 289 AML patients 60 years or older (median age 66, range 60-77 years) undergoing NMA-HSCT (2 or 3 Gray total body irradiation and 3 days of fludarabine 30 mg/m^2). HCT-CI risk was low, intermediate, or high in 36%, 31%, and 33% of patients, respectively. Non-relapse mortality (NRM), cumulative incidence of relapse (CIR), and overall survival (OS) did not differ between HCT-CI groups. The HCT-CI also did not impact outcomes when considering the European LeukemiaNet 2017 risk at diagnosis or the measurable residual disease (MRD) status at HSCT. Notably, MRD-negative older NMA-transplanted AML patients had a beneficial OS of 49% after 5 years. Since a higher HCT-CI did not impair outcomes, age or comorbidities per se should not impede NMA-HSCT, presenting a feasible consolidation option for this group of AML patients.

… transplantation (HCT) choices have been expanded to include older patients and those with comorbidities … about the impacts of multiple comorbidities on outcomes after allogeneic HCT. …

Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases.

Risk assessment of allogeneic hematopoietic cell transplantation (allo-HCT) is hindered by the lack of current data on comorbidities and outcome. The EBMT identified 38,760 allo-HCT recipients with hematologic malignancies transplanted between 2010 and 2018 from matched sibling and unrelated donors with a full data set of pre-existing comorbidities. Multivariate analyses using the Cox proportional-hazards model including known risk factors for non-relapse mortality (NRM) were performed. We found that pre-existing renal comorbidity had the strongest association with NRM (hazard ratio [HR] 1.85 [95% CI 1.55–2.19]). In addition, the association of multiple pre-existing comorbidities with NRM was significant, including diabetes, infections, cardiac comorbidity, and pulmonary comorbidity. However, the HR of the association of these comorbidities with NRM was relatively low and did not exceed 1.24. Consequently, the risk of NRM was only moderately increased in patients with a high hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3 (HR 1.34 [1.26–1.42]). In the current EBMT population, pre-existing non-renal comorbidities determined NRM after allo-HCT to a much lesser extent as compared with the underlying HCT-CI data. Improvements in management and supportive care as well as higher awareness based on the use of HCT-CI may have contributed to this favorable development.

Eligibility assessment of a potential candidate for allogeneic hematopoietic cell transplantation (allo-HCT) is a complex yet vital component of pretransplant evaluation. Although no formal standardized consensus exists to guide this process, transplant centers follow institutional standard operating procedures and parameters to approve candidacy of an individual patient. Consideration for allo-HCT is dependent on a myriad of interrelated factors, including disease-related (eg, appropriate indication, disease status, prior therapies), patient-related (eg, age, functional status, frailty, comorbidities), psychosocial, and economic factors. A multidisciplinary approach is optimal for patient selection and requires the efforts of transplant coordinators, nurses, advanced practice providers, social workers, psychologists, financial specialists, and physicians. This article reviews the data and provides general guidelines that may be used in making an informed decision when evaluating a prospective candidate for allo-HCT. These recommendations are based on published data, expert commentary, reviews, and institutional practices. In the end, the eligibility assessment and decision to consider allo-HCT as the optimal choice of treatment for an individual patient are truly as much an "art" as it is the "science" of medicine, encompassing a multidisciplinary approach to minimize harm without compromising the curative potential-all essential doctrines of the Hippocratic Oath.

… comorbidity indexes such as the Charlson Comorbidity Index, the HCT-CI includes comorbidities … function such as lab values and pulmonary function testing. The HCT-CI score has …

Impact of comorbidities constituting the hematopoietic cell transplant (HCT)â•’comorbidity index on the outcome of patients Page 1 198 | wileyonlinelibrary.com/journal/ejh Eur J …

… , pretransplantation comorbidities and test results, … comorbidities to require intensive care after transplantation. Our observations that the most common pretransplantation comorbidities …

Prospective validation of the hematopoietic cell transplantation-comorbidity index (HCT-CI) using contemporary patients treated with HCT across the Unites States is necessary to confirm its widespread applicability. We performed a prospective observational study including all patients (8115 recipients of allogeneic and 11,652 recipients of autologous HCT) who underwent first HCT that was reported to the CIBMTR between 2007 and 2009. In proportional hazards models, increased HCT-CI scores were independently associated with increases in hazard ratios for NRM (p<0.0001) and overall mortality (p<0.0001) among recipients of allogeneic HCT. HCT-CI Scores of ≥3 were uniformly associated with higher risks for outcomes in both allogeneic and autologous HCT, and all subgroups regardless of diagnoses, age, and conditioning intensity. Recipients of allogeneic HCT with scores of 1–2 who were aged <18 or were treated with lower intensity conditioning regimens had similar outcomes compared to those with score 0. Higher risks for overall mortality, but not for NRM, were observed among recipients of autologous HCT with scores of 1–2 versus 0. Our results confirm the validity the HCT-CI in both allogeneic and autologous HCT. The index should be used as a valid standard-of-care health measure in counseling patients for HCT, in clinical trial design, and in adjusting outcome analyses.

Conventional allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for various hematological diseases due, in part to high-dose conditioning and, in part, to graft-versus-tumor effects. Reduced-intensity or non-myeloablative conditioning regimens have relied mostly on graft-versus-tumor effects for disease control, and their advent has allowed relatively older and medically infirm patients to be offered allo-HCT. However, both HCT modalities have been associated with organ toxicities and graft-versus-host disease, resulting in substantial non-relapse mortality. It has become increasingly important to optimize pre-transplant risk assessment in order to improve HCT decision making and clinical trial assignments. Single-organ comorbidity involving liver, lung, heart, or kidney before HCT has been traditionally found to cause organ toxicity after HCT. Recent efforts have resulted in the advent of a weighted scoring system that could sensitively capture multiple-organ comorbidities prior to HCT. The HCT-comorbidity index (HCT-CI) has provided better prediction of HCT-related morbidity and mortality than other non-HCT-specific indices. Subsequent studies, with the exception of a few studies with modest numbers of patients, have confirmed the prognostic importance of the HCT-CI. Further, the HCT-CI has been consolidated with various disease-specific and patient-specific risk factors to refine assignments of patients to the appropriate HCT setting. Ongoing studies are addressing prospective validation of the HCT-CI, furthering our understanding of biological aging, and enhancing the applicability of the HCT-CI comorbidity coding. Future knowledge of the impacts of multiple comorbidities on post-HCT toxicities might guide new prophylactic and therapeutic interventions to lessen the procedure's mortality.

To evaluate the association between the hematopoietic cell transplantation-comorbidity index (HCT-CI) and the recently developed age-adjusted HCT-CI (HCT-CI/age) and transplant outcomes in the setting of CD34-selected allogeneic HCT, we analyzed a homogeneous population of patients undergoing allogeneic HCT with CD34-selected grafts for acute myeloid leukemia and myelodysplastic syndrome (n = 346). Median HCT-CI and HCT-CI/age scores were 2 (percentile 25 to 75, 1 to 4) and 3 (percentile 25 to 75, 1 to 5), respectively. Higher HCT-CI and HCT-CI/age scores were associated with higher nonrelapse mortality (NRM) and lower overall survival (OS). The HCT-CI distinguished 2 risk groups (0 to 2 versus ≥3), whereas, with the HCT-CI/age, there was a progressive increase in NRM and decrease in OS with increasing scores in all 4 groups (0 versus 1 to 2 versus 3 to 4 versus ≥5). Higher scores in both models were associated with lower chronic graft-versus-host disease relapse-free survival but not with higher relapse. Both models showed a promising predictive accuracy for NRM (c- = .616 for HCT-CI and c- = .647 for HCT-CI/age). In conclusion, the HCT-CI and HCT-CI/age predict transplant outcomes in CD34-selected allo-HCT, including NRM, OS, and chronic graft-versus-host disease relapse-free survival and may be used to select appropriate patients for this approach.

Quantifying the risk of hematopoietic cell transplantation (HCT)–related mortality for pediatric patients is challenging. The HCT-specific comorbidity index (HCT-CI) has been confirmed as a useful tool in adults, but has not yet been validated in children. We conducted a retrospective cohort study of 252 pediatric patients undergoing their first allogeneic HCT between January 2008 and May 2009. Pretransplantation comorbidities were scored prospectively using the HCT-CI. Median age at transplantation was 6 years (range, 0.1-20) and median follow-up was 343 days (range, 110-624). HCT-CI scores were distributed as follows: 0, n = 139; 1-2, n = 52; and 3+, n = 61. The 1-year cumulative incidence of nonrelapse mortality (NRM) increased (10%, 14%, and 28%, respectively; P &lt; .01) and overall survival (OS) decreased (88%, 67%, and 62%, respectively; P &lt; .01) with increasing HCT-CI score. Multivariate analysis showed that compared with score 0, those with scores of 1-2 and 3+ had relative risks of NRM of 1.5 (95% confidence interval, 0.5-4.3, P = .48) and 4.5 (95% confidence interval, 1.7-12.1, P &lt; .01), respectively. These results indicate that the HCT-CI score predicts NRM and OS in pediatric patients undergoing HCT and is a useful tool to assess risk, guide counseling in the pretransplantation setting, and devise innovative therapies for the highest risk groups.

… as the impact of hematopoietic transplantation on the natural history of these comorbid conditions.… community to examine the current methods that assess and score multiple comorbid …

BACKGROUND/PURPOSE Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but advanced age with multiple comorbidities limits the eligibility for allo-HSCT. We conducted a retrospective study to investigate the comorbidities assessments and prognostic factors that predict outcomes for these patients. METHODS Clinical data of patients older than 50 years who had received diagnoses of AML or MDS and underwent allo-HSCT were obtained. Information on patient characteristics, including age, gender, allogeneic transplant type, conditioning regimens, Charlson comorbidity index (CCI), and presence of acute graft-versus-host disease (GVHD) or chronic GVHD, were collected and analyzed. RESULTS Two hundred fifty-five elderly patients with a median age at allo-HSCT of 57 years were included. The significant prognostic factors associated with worse overall survival (OS) were CCI ≥3 (hazard ratio: 1.88) and grade III-IV acute GVHD (3.18). Similar findings were noted in the non-relapse mortality analysis. To investigate the effects of chronic GVHD on patient outcomes, OS analysis was performed for those with survival >100 days after transplantation. The results revealed CCI ≥3 (1.88) and grade III-IV acute GVHD (2.73) remained poor prognostic factors for OS, whereas mild chronic GVHD (0.43) was associated with better OS. CONCLUSION This cohort study suggests that CCI ≥3 predicts poor outcomes, primarily due to a higher NRM risk. Careful management of GVHD after transplantation could improve outcomes in elderly patients with AML or MDS after allo-HSCT.

Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) has enabled better prediction of transplant-related mortality (TRM) in allogeneic hematopoietic stem cell transplants (AHSCT), data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27), in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM) and peripheral blood stem cells (PBSC) as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18–65 years); HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3) in this Brazilian population might justify these results.

… ) was developed at a single center to predict outcomes for allogeneic transplant … HCT-CI predicts NRM and OS in allogeneic transplant recipients at a Canadian center. As the HCT-CI …

Recent advances in allogeneic hematopoietic stem cell transplantation have led to increasing use of this modality in older patients who tend to have been more heavily pretreated and have more comorbidities. Thus, the evaluation of comorbidity is of increasing importance to more precisely assess the benefits and risks of the transplantation procedure. Researchers from Seattle developed the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which was associated with the risk of mortality in several retrospective studies. However, its clinical utility has not been extensively documented in prospective studies. The aim of the present study was to evaluate the utility of the HCT-CI prospectively in a multicenter setting. Overall survival (OS) and nonrelapse mortality (NRM) at 2 years were 59% and 20%, respectively (n = 243). We found that the HCT-CI in its original scale failed to predict OS and NRM in this set of patients. Thus, we applied a flexible HCT-CI risk scoring system (restratifying scores from 0 to 3 to indicate low risk, and scores of 4 or higher as high-risk). The flexible HCT-CI was found to predict 2-year NRM and OS better than the original HCT-CI (NRM: P = .01, OS: P = .003). In subgroup analysis, we evaluated the usefulness of the original HCT-CI for patients excluding those who received cord blood transplantation (n = 186). Both 2-year OS and 2-year NRM were not significantly different according to the original HCT-CI (P = .304, P = .996), but with the flexible HCT-CI, there were significant differences in 2-year OS and 2-year NRM (P = .005 and P = .005, respectively). Multivariate analysis identified age >50, performance status (PS) <90, donor type (HLA-mismatched/unrelated donor), and the flexible HCT-CI ≥4 as significant predictors for worse OS at 2 years. However, the flexible HCT-CI did not remain a significant predictor for NRM at 2 years in multivariate analysis, whereas age, PS, and donor type did. The HCT-CI did not consistently predict both NRM and OS, but it still can be a useful tool in combination with other factors, such as PS and age. Furthermore, the HCT-CI, although potentially useful for capturing pretransplantation comorbidity and risk assessment, may need further validation before its adoption for routine clinical use.

… Taking into account the limits of a retrospective analysis, our results suggest that the HCT-CI should invariably be part of the pretransplant work-up to evaluate transplant-related risks in …

Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk—patients with low/intermediate DRI-R and HCT-CI/Age ≤3 (N = 272); Intermediate-risk—patients with low/intermediate DRI-R and HCT-CI/Age >3 (N = 168); High-risk—patients with high/very high DRI-R and HCT-CI/Age ≤3 (N = 284); and Very high-risk—patients with high/very high DRI-R and HCT-CI/Age >3 (N = 184). Compared with the low-risk group, intermediate, high, and very high-risk groups had a significantly increased risk of death [adjusted HR of 1.37 (P < 0.04), 2.08 (P < 0.001), and 2.92 (P < 0.001), respectively]. The concordance test showed that the HCT-CR model provided better discriminative capacity for OS prediction compared with all prior models independently, including cytogenetic risk group, DRI-R, and HCT-CI/Age model (C-indices: 0.62, 0.55, 0.60, and 0.54, respectively) (P < 0.001). In conclusion, combining disease- and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT.

… (HCT-CI) are associated with worse prognosis following allogeneic hematopoietic cell transplantation (HCT). … characteristics on outcomes of 387 patients undergoing allogeneic HCT for …

Patient comorbidities are being increasingly analyzed as predictors for outcome after hematopoietic stem cell transplantation (HSCT), especially in allogeneic HSCT (Allo-HSCT). Researchers from Seattle have recently developed several pretransplant scoring systems (hematopoietic cell transplantation comorbidity index [HCT-CI] and the Pretransplantation Assessment of Mortality (PAM) model) from large sets of HSCT recipients with the aim of improving non-transplant models, mainly the Charlson Comorbidity Index (CCI). The validation of these comorbidity indexes in other institutions and in different disease and conditioning-related settings is of interest to determine whether these models are potentially applicable in clinical practice and in research settings. We performed a retrospective study in our institution including 194 consecutive reduced-intensity conditioning (RIC) AlloHSCT (allo-RIC) recipients to compare the predictive value of the PAM score, CCI, the original HCT-CI, and the flexible HCT-CI using a different risk group stratification. The median patient pretransplant scores for the HCT-CI, PAM, and CCI were 3.5, 22, and 0, respectively. The flexible HCT-CI risk-scoring system (restratified as: low risk [LR] 0-3 points, intermediate risk [IR] 4-5 points, and high risk [HR] >5 points) was the best predictor for non-relapse mortality (NRM). The 100-day and 2-year NRM incidence in these risk categories was 4% (95% confidence interval C.I. 2%-11%), 16% (95% C.I. 9%-31%), and 29% (95% C.I. 19%-45%), respectively (P < .001), and 19% (95% C.I. 12%-28%), 33% (95% C.I. 22%-49%), and 40% (95% C.I. 28%-56%), respectively (P=.01). However, we found no predictive value for NRM using neither the original HCT-CI nor the PAM or CCI models. The better predictive capacity for NRM of the flexible HCT-CI than PAM and CCI was confirmed with the c-statistics (c-statistics of 0.672, 0.634, and 0.595, respectively). Regarding the 2-year overall survival (OS), the flexible HCT-CI score categories were also associated with the highest predictive HR. In conclusion, our single-center study suggests that the flexible HCT-CI is a good predictor of 2-year NRM and survival after an allo-RIC.

… such as the HCT-CI would be useful for AYAs. We conducted a retrospective cohort study to determine the validity of the HCT-CI in a cohort of AYA patients undergoing allogeneic HCT. …

BACKGROUND Allogeneic hematopoietic cell transplantation (HCT) outcomes may be predicted by published risk scores; however, the ideal system has not been identified for acute leukemias. PATIENTS AND METHODS We retrospectively examined the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), modified European Group for Blood and Marrow Transplantation (mEBMT), EBMT-Alternating Decision Tree (ADT), and others on 231 patients with acute leukemia. RESULTS Acute myeloid leukemia was diagnosed in 200 patients, and acute lymphocytic leukemia was diagnosed in 31 patients. For HCT-CI, patients were grouped as 0 to 1, 2 to 3, and > 3. For mEBMT, patients were grouped as 0 to 2, 3, and > 3. For EBMT-ADT, the 100-day mortality was calculated and grouped as ≤ 4.1%, 4.1% to 11.5%, and > 11.5%. Higher HCI-CI demonstrated inferior overall survival (P = .04; c-statistic, 0.57), whereas mEBMT and EBMT-ADT did not stratify well. A new weighted score was developed that assigned 1 point for age ≥ 60 years, acute lymphocytic leukemia diagnosis, mismatch unrelated or haploidentical donor, cardiovascular comorbidity, and pre-transplant diabetes, whereas arrhythmia received 2 points. The new weighted score assigned 0 points to 88 (38%), 1 to 2 points to 121 (52%) and ≥ 3 points to 22 (10%) patients, and demonstrated improved prognostic capability compared with the other scores (P = .0001; c-statistic, 0.61). CONCLUSIONS The HCT-CI stratifies patients with leukemia for overall survival but is inferior to our single-center score, which is influenced by cardiac comorbidity and arrhythmia. Differences in pre-transplant risk scores may be related to different transplant practices.

The Hematopoietic Cell Transplant Co-morbidity Index (HCT-CI, Sorror et al 2005) was developed as a prognostic tool for overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic cell transplant (HCT) patients. The prognostic significance of the score for patients with acute myeloid leukemia (AML) undergoing HCT has been demonstrated, however reports are conflicting. The purpose of this single-center study was to retrospectively investigate the prognostic impact of the individual component co-morbidities of the HCT-CI on the outcome of 418 patients that underwent HCT for AML at our center between 2000 and 2013. Patients underwent HCT in first (CR1, n=303) and second (CR2, n=115) complete remission. Median age at HCT was 50 years (range 18-71), 212 (51%) patients were female. Myeloablative conditioning (MAC) was used in 283 (68%) patients, reduced-intensity (RIC) in 135 (32%) patients. Donors were related for 236 (56%) patients, unrelated for 182 (44%) patients. Grafts were peripheral blood stem cells (PBSC) in 339 (81%) patients and bone marrow in 79 (19%) patients. Median follow-up of patients alive was 62 months (range 12-168). Cytogenetics at diagnosis were available for 84% of patients, of which 31 (7%) were favorable, 246 (59%) were intermediate and 74 (18%) were unfavorable risk (MRC classification). HCT-CI scores were grouped as 0 (n=109, 26%), 1-2 (n=157, 38%) and ≥3 (n=152, 36%). A total of 171 patients (41%) underwent HCT during the years 2000-2006 and 247 patients (59%) during the years 2007-2013. The observed frequency of the co-morbidities composing the HCT-CI is summarized in Table 1. Univariate analysis for OS demonstrated the following significant variables: Age (HR=1.02, 95%CI=1.01-1.03, p=0.0002), CR status (HR=1.42 for CR2, 95%CI=1.08-1.87, P=0.01), donor type (HR=0.73 for related, 95%CI=0.57-0.94, p=0.02), HCT-CI group (overall p-value=0.004). For OS, univariate analysis of the impact of individual co-morbidities was performed for the components of the HCT-CI score that were observed in ≥5% of the patients (Table 1). All variables with a p-value ≤0.2 were introduced into the multivariable analysis (not including the HCT-CI itself), and these included cardiac disorder (CAD, CHF, MI or EF≤50%) (HR=1.65, 95%CI=1.17-2.32, p=0.004), prior solid tumor (HR=1.56, 95%CI=1.06-2.30, p=0.02) and diabetes (HR=1.40, 95%CI=0.89-2.19, p=0.14). In the multivariable analysis for OS, none of the aforementioned co-morbidities demonstrated independent prognostic relevance. For NRM, univariate analysis demonstrated cardiac disorder (HR=1.89, 95%CI=1.27-2.81, p=0.002), diabetes (HR=1.94, 95%CI=1.20-3.12, p=0.007) and moderate pulmonary (FEV1 and/or DLCO 66-80% or dyspnea on slight activity) (HR=1.31, 95%CI=0.93-1.84, p=0.12) to meet the significance criteria for inclusion in the multivariable analysis, which finally demonstrated diabetes (HR=2.17, 95%CI=1.31-3.60, p=0.003) and cardiac disorder (HR=1.78, 95%CI=1.15-2.76, p=0.01) to be independent predictors of NRM post-transplant. In conclusion, among the pre-transplant co-morbidities included in the HCT-CI, diabetes and cardiac dysfunction are independent prognostic indicators for NRM but not for OS. Pulmonary dysfunction does not seem to negatively influence outcomes in this cohort of patients. Disclosures Kim: Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

Allogeneic hematopoietic cell transplantation (HCT) can cure many non-malignant conditions but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, paediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children, adolescents and young adults (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2,815 children and AYAs (<40yo) who received first allogeneic HCT for non-malignant diseases from 2008–2017 were included to create an expanded youth non-malignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently – history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), underweight (14.5%). 39% of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1–2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (HR 1.41, 95% CI 1.01–1.98). Modifications to the HCT-CI can benefit children and AYA patients with non-malignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population.

… had the poorest outcomes. Therefore, we found that HCT-CI is associated with the outcomes of … Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective …

Allogeneic hematopoietic cell transplantation is a curative procedure for hematologic malignancies but is associated with a significant risk of non-relapse mortality (NRM). The Hematopoietic Cell Transplantation– Comorbidity Index (HCT-CI) is a prognostic tool that discriminates this risk in all age groups. A recent survey of transplant physicians demonstrated that 79% of pediatric providers used the HCT-CI infrequently, and most reported concerns about its applicability in the younger population. We conducted a retrospective study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of expanded HCT-CI definitions on NRM in pediatric and young adult patients with hematologic malignancies. We included 5,790 patients <40 years old receiving allogeneic transplant between 2008 and 2017 to examine broader definitions of comorbidities in the HCT-CI, including history of mechanical ventilation and fungal infection, estimated glomerular filtration rate (eGFR), and body mass index (BMI) percentiles. Multivariable Fine-Gray models were created to determine the effect of each HCT-CI defining comorbidity and its modification on NRM, and were utilized to develop two novel risk scores. We next developed the expanded HCT-CI for children and young adults (youth with malignancies; expanded ymHCT-CI), where 23% patients had an increased comorbidity score, compared to the HCT-CI. Comorbidities with hazard ratio (HR) <1.2 were then removed to create the simplified HCT-CI for children and young adults (youth with malignancies; simplified ymHCT-CI), which demonstrated higher scores corresponded to a greater risk of NRM (p<0.001). These novel comorbidity indices with broader definitions are more relevant to pediatric and young adult patients, and prospective studies are needed to validate these in the younger patient population. It remains to be seen if the development of these pediatric-specific and practical risk indices increases their utilization by the pediatric transplant community.

We have carried out HLA-matched unrelated donor hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in patients with hematologic malignancies who were ineligible for conventional transplantations because of age, comorbidities, or both. The nonmyeloablative regimen consisted of 90 mg/m2 fludarabine and 2 Gy total body irradiation given before and mycophenolate mofetil and cyclosporine given after HCT. This report compares, retrospectively, morbidity and mortality among 60 consecutive patients given nonmyeloablative conditioning (nonablative patients) to those among 74 concurrent and consecutive patients given myeloablative conditioning (ablative patients) before unrelated HCT. The Charlson Comorbidity Index was used to assess pretransplantation comorbidities. Even though nonablative patients had significantly higher pretransplantation comorbidity scores, were older, and had more often failed preceding ablative transplantations and cytotoxic therapies, they experienced fewer grades III to IV toxicities than ablative patients. Further, the incidence of grades III to IV acute graft-versus-host disease (GVHD) was significantly lower in nonablative patients. Both patient groups had comparable 1-year probabilities of chronic GVHD. The 1-year nonrelapse mortality rate was 20% in nonablative patients compared to 32% in ablative patients (hazard ratio = 1.4). After adjustment for pretransplantation differences between the 2 patient groups, the hazard ratio was 3.0 (P = .04). Multivariate analyses showed higher pretransplantation comorbidity scores to result in increased toxicity and mortality.

The hematopoietic cell transplantation specific comorbidity index (HCT-CI) has been recently proposed to predict the probability of nonrelapse mortality (NRM) and overall survival (OS) in allogeneic HCT recipients while taking into account any pretransplant comorbidity. We tested the validity of the HCT-CI in a cohort of 373 adult HCT recipients (184 matched-related donor and 189 unrelated umbilical cord blood) who received a myeloablative (N = 150) or nonmyeloablative (N = 223) conditioning regimen. HCT-CI scores of 0, 1, 2, and > or =3 were present in 58 (16%), 56 (15%), 64 (17%), and 195 (52%) patients, respectively. Pulmonary conditions were the most common comorbidity. Cumulative incidence of NRM at 2 years was 10%, 20%, 24%, and 28% for HCT-CI scores of 0, 1, 2, and > or =3, respectively (P = .01). The corresponding probability of OS at 2 years was 72%, 67%, 51%, and 48%, respectively (P < .01). On multivariate analyses adjusted for recipient age, disease risk, donor source, and conditioning regimen intensity, the relative risks for NRM for HCT-CI scores of 1, 2, and > or =3 (compared to a score of 0) were 2.0 (95% confidence intervals, 0.8-5.3), 2.6 (1.0-6.7), and 3.2 (1.4-7.4), respectively. The risks for overall mortality were 1.2 (0.6-2.1), 2.0 (1.1-3.4), and 2.1 (1.3-3.3), respectively. In subgroup analyses, the HCT-CI score did not consistently predict NRM and OS among different donor sources and conditioning regimens. The HCT-CI, although a useful tool for capturing pretransplant comorbidity and risk-assessment, needs to be further validated prior to adopting it for routine clinical use.

… A modified EBMT risk score and the hematopoietic cell transplantation-specific comorbidity index for pre-transplant risk assessment in adult acute lymphoblastic leukemia. …

So far, prognostic evaluation of patients with myelodysplastic syndrome has mainly been based on disease-related parameters like cytopenias, karyotype, or percentage of blast cells in the bone marrow. Patients’ characteristics reflecting comorbidities like cardiovascular diseases and impaired renal or liver function were not taken into account. In this study, the authors found that the Hematopoietic Cell Transplantation Comorbidity Index (HCTCI) may be useful for patients with myelodysplastic syndrome receiving best supportive care only. See perspective article on page 602. We studied the impact of comorbidities on survival and evaluated the prognostic utility of comorbidity scores in MDS patients, who received best supportive care and were assessable according to the Charlson Comorbidity Index (CCI) and the Hematopoietic Stem Cell Transplantation Comorbidity Index (HCTCI): 171 patients were identified in the Duesseldorf MDS Registry. The HCTCI captured more comorbidities. Both scoring systems had prognostic relevance, but the HCTCI more clearly distinguished between low-, intermediate- and high-risk patients. Median survival times of the different risk groups according to the HCTCI were 68, 34 and 25 months, respectively. The HCTCI showed prognostic impact in the IPSS intermediate- and high-risk group. On multivariate regression analysis, only the HCTCI remained a prognostic factor independent of IPSS. Considering their prognostic impact, comorbidities of MDS patients should receive appropriate attention in clinical trials as well as day-to-day clinical decision making.

Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50–73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59–3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14–2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07–2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13–2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54–4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults.

Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients.

Allogeneic hematopoietic cell transplantation (alloHCT) in older patients requires the weighing of risks and benefits for this potentially curative treatment while facing age-related …

Allogeneic hematopoietic cell transplantation (alloHCT) has been increasingly offered to older adults with hematologic malignancies. However, optimal methods to determine fitness for alloHCT have yet to be defined. We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict post-alloHCT outcomes in a single-center prospective cohort study of patients aged 50 and older. Outcomes included overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM). A total of 148 patients were included, with median age 62 years (range 50–76). In multivariate regression analysis, several CGA measures of functional status were predictive of post-alloHCT outcomes, after adjusting for traditional prognostic factors. Any deficit in Instrumental Activities of Daily Living (IADL) was associated with inferior OS (hazard ratio [HR] 1.81,95% confidence interval [CI] 1.07–3.08, p=0.03) and PFS (HR 1.85, 95% CI 1.15–2.99, p=0.01). Medical Outcomes Study Physical Health scale (MOS-PH) score <85 was associated with inferior OS (HR 1.96, 95% CI 1.13–3.40, p=0.02), PFS (HR 1.75, 95% CI 1.07–2.88, p=0.03), and increased NRM (subdistribution HR 2.57, 95% CI 1.12–5.92, p=0.03). MOS-PH was also associated with the number of non-hematologic grade >3 adverse events within the first 100 days after alloHCT (rate ratio 1.61,95% CI 1.04–2.49, p=0.03). These findings support previous work suggesting that IADL is an important prognostic tool prior to alloHCT. MOS-PH is newly identified as an additional metric to identify older patients at higher risk of poor post-alloHCT outcomes, including toxicity and NRM.

Use of allogeneic hematopoietic cell transplantation (alloHCT) is increasing in older patients with hematologic malignancies. Studies suggest that geriatric assessment (GA), incorporating functional measures such as instrumental activities of daily living (IADL), delineates subtle age-related impairments that enhance risk-stratification. The objective of this multi-institutional retrospective study was to evaluate the prognostic utility of GA metrics collected pre-alloHCT. Eligibility criteria included age ≥50 and pre-alloHCT GA inclusive of at least IADL. Beyond IADL, additional geriatric metrics were collected where available and included Medical Outcomes Study Physical Health score (MOS-PH), Timed Up and Go (TUG), and cognition by Blessed Orientation Memory Concentration (BOMC). Three hundred thirty subjects were included, with a median age of 63 (range 50 to 77). Impairments were frequent: 36% had at least 1 IADL impairment; 14% had TUG ≥13.5 seconds; and 17% had cognitive impairment (BOMC ≥ 7). Median MOS-PH score was 80. IADL and age were not significantly associated with nonrelapse mortality (NRM) or overall survival (OS). In multivariate analysis, only impaired cognition and Hematopoietic Cell Transplant-Comorbidity Index score ≥3 showed an independent association with 1-year NRM (subdistribution hazard ratio [SHR], 2.36; P = .01; and SHR, 2.19; P = .009, respectively). Cognitive impairment independently conferred inferior 1-year OS (hazard ratio, 1.94; P = .01). In a preplanned subgroup analysis in 224 patients aged ≥60 years, cognitive impairment remained the sole GA metric predictive of NRM (2-year NRM: SHR, 2.72; P = .007). These data suggest that cognitive impairment elevates risk of post-alloHCT NRM in older patients.

Limitations found on geriatric assessment (GA) track with worse outcomes after hematopoietic cell transplantation (HCT). We report on a multidisciplinary team clinic (MDC), consisting of a cancer-specific GA and a multidisciplinary team of providers, to assess candidacy and create an individualized optimization plan for allogeneic HCT candidates aged ≥60 years and autologous HCT and adoptive T-cell therapy candidates aged ≥70 years. Among the 247 patients evaluated in the MDC, allogeneic HCT candidates comprised the majority (60%), followed by autologous HCT (37%) with occasional older cellular therapy candidates (3%). Almost all patients meeting program-required minimum ages for MDC optimization at our institution were assessed (98%). Relative to historical control subjects undergoing GA alone, allogeneic HCT patients aged ≥60 years who underwent MDC appraisal had similar frequencies of high-risk disease, reduced intensity regimens, and high comorbidity but fewer GA-graded functional impairments. The MDC cohort experienced fewer inpatient deaths, shorter length of stay, and fewer discharges to nursing facilities compared with control subjects. Improvements in early mortality were observed over time; 1-year overall survival improved from 43% in the pre-MDC era to 70% in the recent MDC era, and 1-year nonrelapse mortality decreased from 43% to 18%. The 31 autologous HCT recipients aged ≥70 years optimized by the MDC achieved 0% nonrelapse mortality and 97% overall survival at 1 year. A GA-guided MDC for older HCT candidates is feasible and seems to reduce transplant-associated morbidity and mortality. An MDC should encourage broader and safer utilization of transplantation in older patients.

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains—physical, cognitive, nutritional, and psychological—at 2 time points prior to HCT—new patient evaluation (NPE) and sign-off (SO)—between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.

… In summary, a comprehensive geriatric assessment with FIL score seems to add significant prognostic information in elderly patients submitted to allo-SCT. The pretransplant adoption …

Hematologic malignances are more common and often higher risk in older patients. Allogeneic hematopoietic cell transplantation (alloHCT) best enables long-term disease control for patients with poor risk or relapsed/refractory hematologic malignancies such as acute myeloid leukemia, myelodysplastic syndromes, or myelofibrosis. Rates of alloHCT among older patients, while still relatively low compared with younger patients, have risen sharply over the past decade. Accumulating evidence supports alloHCT for patients ≥60 years of age relative to non-HCT therapies based on improved overall and disease-free survival. However, a significant proportion of older adults have limitations characterized by geriatric assessment. A systematic process to evaluate and optimize older patients may improve decision making, transplant outcomes, and alloHCT access. We present case-based studies to illustrate a stepwise and rational approach to proper older patient evaluation, pretransplant optimization, and posttransplant care with attention to important geriatric issues and quality of life.

Background Older patients who receive hematopoietic cell transplantation (HCT) may be at risk for adverse outcomes due to age-related conditions or frailty. Geriatric assessment (GA) has been used to evaluate HCT candidates but can be time-consuming. We therefore sought to determine the predictive ability of two screening tools, the Vulnerable Elders Survey (VES-13) and the G8, for abnormal GA or frailty. Materials and Methods We enrolled 50 allogeneic HCT candidates age ≥60 years. The GA included measures of medical, physical, functional, and social health. Frailty was defined as 3 or more abnormalities on grip strength, gait speed, weight loss, exhaustion, and activity. We associated baseline characteristics and abnormal GA or frailty. We determined the sensitivity and predictive ability of the VES-13 and G8 for GA and frailty. Results Overall, 33 (66%) patients (mean age 65.4 years) had an abnormal GA, and11 patients (22%) were frail. The G8 screening tool had a higher sensitivity for an abnormal GA (69.7%), and the VES-13 had a higher specificity (100%). Both tools had similar discriminatory ability. Conclusions Older HCT candidates had a significant number of deficits on baseline GA and a high prevalence of frailty. Existing screening tools may not be able to replace a full GA.

Haematopoietic stem-cell transplantation (HSCT) has seen substantial growth among older adults. Chronological age is no longer viewed as an absolute barrier to HSCT, and alternative methods for assessing pre-transplantation fitness are increasingly used. In this Series paper, we summarise the metrics for pre-transplantation risk assessment in older adults, including both traditional metrics and geriatric assessment, and the ability of these metrics to predict post-transplantation outcomes. We also discuss strategies to broaden the utility of geriatric assessment, including in chronologically younger HSCT candidates and to guide individualised pre-transplantation interventions. Finally, we discuss donor considerations in older adults, including use of older sibling donors, haploidentical donors, and emerging data for donor-associated clonal haematopoiesis of indeterminate potential.

Geriatric assessment (GA) may identify vulnerabilities and promote risk-stratification in older adults predisposed to toxicities after autologous (auto), allogeneic (allo) hematopoietic cell transplantation (HCT) and chimeric antigen T-cell therapies (CAR T). With increased utilization cellular therapies for older adults the American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines and its Special Interest Group for Aging (SIG) conducted an online cross-sectional survey between April 2023 and August 2023 to determine transplantation and cellular therapy physicians' practice patterns regarding GA in older patients receiving HCT and CAR T-cell therapies. E-mail surveys were sent to 1168 ASTCT physician members and only 96 (8.2%) respondents completed the survey. Most (86%) were affiliated with university/teaching centers and 70% had a combined HCT and cellular therapy practice. More than 50% of respondents were interested in pursuing GA but 68% described barriers. The top two recognized barriers to GA were lack of time (96%) and clinical support staff (90%). Despite interest, only 15% respondents reported to know the domains of GA 'well'. Among those using GA, the minimum age used for routine GA was 65 years for allo-HCT and CAR T in over 91% respondents. Taken together, we recommend the HCT community leadership and GA experts combine efforts to address the gap in GA uptake and implementation.

… geriatric assessments into the optimization of older patients for hematopoietic stem cell transplantation and … Geriatric assessment to predict survival in older allogeneic hematopoietic cell …

OBJECTIVES To evaluate the results of the comprehensive geriatric assessment (CGA) before allogeneic hematopoietic stem cell (HSCT) transplantation in patients aged 60 years and over. METHODS We evaluated all consecutive patients undergoing CGA before HSCT between September 2011 and July 2018 in a private hospital in Brazil. We also evaluated the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-SCI) and the Disease Risk Index (DRI). RESULTS During the study period, 61 patients were referred for transplant evaluation. After exclusions, we analyzed 40 patients, with a mean age of 67.6 years (60-76). The CGA detected vulnerability and frailty in 43% and 18.9% respectively according to the Fried Frailty Phenotype score; limitations across the domain of function and disability with handgrip test alterations in 65.8%. However, 36 (90%) were independent for instrumental activities of daily living (IADL). Cognitive and depression domain have shown abnormal with the clock test in 44.4%, and loss of memory complains in 37.5%. But the mini-mental test was normal in 89%. Geriatric Depression Scale (GDS) was normal in 82.5%. 30% were considered at risk for malnutrition. Half of the patients (50%) had a high Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score. 32.5% needed ICU admission. The overall survival and non-relapse mortality at 2 years were 41.8% and 38.7% respectively. CONCLUSION The CGA was feasible in detecting the patients' vulnerabilities in our population. More studies, multicentric and with a larger number of patients, are needed to evaluate the role of CGA in this context of allo-HCT in our population.

ABSTRACT Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) has seen marked growth among older adults, where chronological age is no longer a barrier to transplant. As allo-HCT expands to older and potentially less fit individuals, prognosticating transplant outcomes in this population remains an ongoing need. Areas covered: This review summarizes pre-transplant assessment tools in optimizing patient selection and predicting transplant outcomes in older adults, including comorbidity indices, psychosocial assessment, geriatric assessment, serum biomarkers, and disease risk. This review also discusses the impact of donor age and clonal hematopoiesis of indeterminate significance on transplant outcomes. Expert commentary: Determining which patients should be referred for transplant remains challenging, especially in older adults. Chronological age is an insufficient prognostic metric, and refining, validating, and developing novel pre-transplant risk assessment tools for geriatric patients offers great potential benefit to the field.

Background Despite improvements in conditioning regimens and supportive care having expanded the curative potential of HCT, underutilization of HCT in older adults persists (Bhatt VR et al, BMT 2017). Therefore, we conducted a survey of transplant physicians (TP) to determine their perceptions of the impact of older age (≥60 years) on HCT candidacy and utilization of tools to gauge candidacy. Methods We conducted a 23-item, online cross-sectional survey of adult physicians recruited from the Center for International Blood and Marrow Transplant Research between May and July 2019. Results 175/770 (22.7%) TP completed the survey; majority of respondents were 41-60 years old, male, and practicing in a teaching hospital. Over 75% were at centers performing ≥50 HCT per year. When considering regimen intensity, most (96%, n=168) had an upper age limit (UAL) for using a myeloablative regimen (MAC), with only 29 physicians (17%) stating they would consider MAC for patients ≥70 years. In contrast, when considering a reduced intensity/non-myeloablative conditioning (RIC/NMA), 8%, (n=13), 54% (n=93), and 20% (n=35) stated that age 70, 75, and 80 years respectively would be the UAL to use this approach, with 18% (n=31) reporting no UAL. TP agreed that Karnofsky Performance Score (KPS) could exclude older pts for HCT, with 39.1% (n=66), 42.6% (n=72), and 11.4% (n=20) requiring KPS of ≥70, 80, and 90, respectively. The majority (n=92, 52.5%) indicated an HCT-comorbidity index threshold for exclusion, mostly ranging from ≥3 to ≥ 5. Almost all (89.7%) endorsed the need for a better health assessment of pre-HCT vulnerabilities to guide candidacy for pts ≥60 with varied assessments being utilized beyond KPS (Figure 1). However, the majority of centers rarely (33.1%) or never (45.7%) utilize a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates ≥60 yrs. The largest barriers to performing GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff (Figure 2). Approximately half (n=78, 45%) endorsed GA now routinely influences candidacy. Conclusions The vast majority of TP will consider RIC/NMA alloHCT for patients ≥70 years. However, there is heterogeneity in assessing candidacy. Incorporation of GA into a standardized and easily applied health assessment tool for risk stratification is an unmet need. The recently opened BMT CTN 1704 may aid in addressing this gap.

Older patients with hematological malignancies are increasingly considered for hematopoietic cell transplantation (HCT) [1]. The selection of an appropriate older candidate has historically been based on the clinician’s subjective assessment and the HCT comorbidity index (HCT-CI) [2–4]. Recently, comprehensive geriatric assessment (CGA) has emerged as a risk stratification tool for survival outcomes and treatment toxicities in older patients with advanced hematological malignancies [5, 6]. For HCT patients, specific domains of CGA such as instrumental activities of daily living (IADL) and gait speed may predict survival [7], however, the impact of CGA on transplant decision-making and treatment-related toxicities have not been reported. In this retrospective study, we identified all patients who were referred to the outpatient geriatrics service prior to a planned HCT from 2011 to 2017 at our institution. Findings from the pre-HCT CGA and clinical, demographic, and outcome data were extracted from the electronic medical record using standard methods. CGA was performed by a member of the geriatrics team according to the published standard for cancer patients [8] and incorporated a patientcentered assessment in the form of an electronic rapid fitness assessment (eRFA) in the last 2 years [9]. Components of CGA included assessment of basic and instrumental activities of daily living (ADL/IADL); cognition (Montreal cognitive assessment, MoCA); nutrition (mini nutritional assessment, MNA); medication review; fall risk; depression (geriatric depression scale, GDS); and mobility and muscle strength (timed up and go test) [8, 9]. We then systemically collected all grade 3 or higher toxicities according to CTCAE version 4.3 during the peri-transplant period up to day 100 for transplanted patients as described previously [10–12]. For patients who did not undergo transplant, we inquired the primary physician and reviewed medical decision-making and subsequent plans of action as documented in the electronic medical record. In total, 59 geriatric referrals were made during the period, with 51% of them during the last 2 years (30 out of 59). The referrals were based on transplant physicians’ clinical assessment of individual patients, since no standard triggers existed at our institution. After excluding 11 patients with post-HCT referrals, we analyzed a cohort of 48 patients with pretransplant CGA (Table 1). Fifteen patients underwent autologous HCT, 18 patients allogeneic HCT, and 15 patients did not undergo HCT. The main reasons for forgoing HCT in these 15 patients were overall poor performance status/comorbidities (60%), patient decision (27%), and rapid disease relapse/progression (13%). For the 33 patients who underwent transplant, the median number of days from CGA to HCT was 32 (interquartile range, 16.8–48.8). During a median follow-up of 13 months for survivors, 11 patients (9 in the allogeneic group and 2 in the autologous group) died giving an estimated 1-year overall survival of 78% (95% CI, 0.58–0.90), with 91% (95% CI, 0.52–0.99) and 70% (95% CI, 0.42–0.86) for autologous or allogeneic patients, respectively. Day 100 mortality rate was 9% for the whole group. Overall, the causes of death were relapse (n= 5, 45%), sepsis/infection * Richard J. Lin linr@mskcc.org

A new hematopoietic cell transplantation–specific comorbidity index (HCT-CI) was effective in predicting outcomes among patients with hematologic malignancies who underwent HCT at Fred Hutchinson Cancer Research Center (FHCRC). Here, we compared the performance of the HCT-CI to 2 other indices and then tested its capacity to predict outcomes among 2 cohorts of patients diagnosed with a single disease entity, acute myeloid leukemia in first complete remission, who underwent transplantation at either FHCRC or M. D. Anderson Cancer Center (MDACC). FHCRC patients less frequently had unfavorable cytogenetics (15% versus 36%) and HCT-CI scores of 3 or more (21% versus 58%) compared with MDACC patients. We found that the HCT-CI had higher sensitivity and outcome predictability compared with the other indices among both cohorts. HCT-CI scores of 0, 1 to 2, and 3 or more predicted comparable nonrelapse mortality (NRM) among FHCRC and MDACC patients. In multivariate models, HCT-CI scores were associated with the highest hazard ratios (HRS) for NRM and survival among each cohort. The 2-year survival rates among FHCRC and MDACC patients were 71% versus 56%, respectively. After adjustment for risk factors, including HCT-CI scores, no difference in survival was detected (HR: 0.98, P = .94). The HCT-CI is a sensitive and informative tool for comparing trial results at different institutions. Inclusion of comorbidity data in HCT trials provides valuable, independent information.

… Finally, we studied a cumulative HCT-CI score ≥ 3 points as an independent comorbid condition. Non-relapse mortality (NRM) was defined as death without the competing event of …

… for non-relapse mortality (NRM) risk and overall survival (OS) among 5888 adults who underwent PTCY-based allo-HCT … main drivers of non-relapse mortality (NRM) after allo-HCT. The …

Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo‐HCT) is essential for estimating non‐relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of ‘high‐yield’ comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34‐selected allo‐HCT. Here, we evaluated the SCI in a single‐centre cohort of 327 patients receiving reduced‐intensity conditioning followed by unmanipulated allografts from HLA‐matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0–1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3‐year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all‐cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1‐, 2‐ and 3‐year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo‐HCT from HLA‐matched donors after reduced‐intensity conditioning.

Allogeneic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDS) but is severely limited by non-relapse mortality (NRM), especially in this mostly old population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years the age at which transplants are made has been progressively increasing and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study of the European Group for Blood and Marrow Transplantation (EBMT) registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDS between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47% respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio for NRM. In multivariate analysis, age-band (HR 1.13; 95% CI, 1.02 to 1.25, p=0.016), HCT-CI ≥ 3 (HR 1.34; 95% CI, 1.04 to 1.73, p=0.022) and KPS ≤80 (HR 2.03; 95% CI, 1.52 to 2.73, p<0.0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDS.

… HCT-CI scores at the time of cGVHD cohort enrollment were associated with higher non-relapse mortality … for measuring comorbidity in patients with cGVHD, so we used the HCT-CI and …

Non-relapse mortality (NRM) remains a major and often unavoidable adverse event following allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly among older adults and patients with multiple comorbidities. Although the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is widely used for risk assessment, its predictive performance for NRM is limited, particularly for capturing functional status and physiological reserve. Sarcopenia, a marker of physical frailty and reduced physiological reserve, has recently emerged as a potential prognostic marker in transplant populations. This study aimed to determine whether combining pre-transplant sarcopenia with the HCT-CI improves NRM risk stratification after allo-HSCT. We retrospectively analyzed 95 adult patients who underwent their first allo-HSCT at our institution between May 2017 and December 2024. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria using standardized assessments of handgrip strength, gait speed, and skeletal muscle mass index. Patients were classified into high-risk (sarcopenia plus HCT-CI ≥ 3) or low-risk (others) groups. Compared with the low-risk group, the high-risk group showed significantly higher 2-year cumulative incidence of NRM (41.7% vs. 16.1%, p=0.026) and poorer overall survival (33.3% vs. 71.0%, p=0.002). In multivariable analysis, the composite high-risk classification independently predicted NRM (subdistribution hazard ratio 3.48, 95% confidence interval, 1.26-9.64, p=0.018), while sarcopenia or HCT-CI alone did not. These findings suggest that integrating physical reserve and comorbidity potentially enhances NRM risk stratification after allo-HSCT. The composite index may provide a practical framework to help optimize conditioning intensity, guide prehabilitation strategies, and personalize post-transplant management.

… (HCT). This retrospective study was done to assess the impact of the HCTcomorbidity index (HCT-… The OS and non-relapse mortality (NRM) were 56% and 30% at 2 years, respectively. …