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Beyond Age and Performance Status: Frailty and Fitness Assessment for Hematopoietic Cell Transplantation and CAR T-Cell Therapy

The following article is the sole perspective of the authors and does not necessarily represent the opinion of ASTCT.

Frailty and fitness assessment have become increasingly important in determining eligibility for hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR) T-cell therapy. Chronological age and conventional performance status alone do not adequately characterize physiologic reserve or vulnerability to treatment-related complications.

This is particularly important as the field has increasingly moved away from excluding patients from potentially life-sustaining therapies based on single characteristics, such as chronological age, that may not accurately reflect treatment tolerance or anticipated benefit. Geriatric assessment provides a multidimensional evaluation that extends beyond comorbidity to include physical and functional status, cognition, psychological health, nutrition, medications and polypharmacy, and social support (Jayani, 2023; Muffly et al., 2013; Muffly et al., 2014).

Frailty Assessment Tools and Evidence

Numerous frailty and geriatric assessment instruments have been evaluated in patients with hematologic malignancies, but these instruments assess different domains and may classify the same patient differently. Objective measures such as gait speed, grip strength, activities of daily living (ADLs), instrumental activities of daily living (IADLs), and the Short Physical Performance Battery (SPPB) can identify vulnerabilities that may not be apparent from Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status alone.

For example, a prospective study of older allogeneic HCT (allo-HCT) recipients showed that limitations in IADLs, slow walking speed, higher HCT-CI, impaired mental health, and elevated C-reactive protein independently predicted inferior survival (Muffly et al., 2013). These observations support combining conventional transplant risk assessment with multidimensional geriatric and functional assessment (Muffly et al., 2013; Muffly et al., 2014).

Recent transplantation and cellular therapy initiatives increasingly recognize the potential value of geriatric assessment. An ASTCT survey demonstrated substantial heterogeneity in current practice and showed that many transplant physicians do not consider either Karnofsky performance status or HCT-CI alone sufficient for determining fitness in older HCT candidates (Farhan et al., 2025; Munshi et al., 2025). Comprehensive geriatric assessment (CGA), or a focused multidomain assessment when full CGA is impractical, therefore represents an important framework for evaluating physiologic reserve. Emerging inflammatory, immune, metabolic, and aging-related biomarkers may eventually complement clinical frailty assessment, but they currently remain investigational and should not replace functional and clinical evaluation (Farhan et al., 2025; Munshi et al., 2025).

Treatment-Specific Definitions of Fitness

Fitness for HCT and CAR T therapy should be considered a multidimensional and treatment-specific construct rather than a binary determination based solely on chronological age, performance status, or comorbidity burden alone. Although allogeneic HCT, autologous HCT, and CAR T therapy share important vulnerabilities associated with aging, their physiologic demands and competing risks differ substantially.

Allo-HCT requires sufficient reserve to tolerate conditioning-related toxicity, prolonged immunosuppression, graft-versus-host disease (GVHD), infectious complications, and extended functional recovery. Autologous HCT has a greater emphasis on tolerance of high-dose chemotherapy, hematologic recovery, infection risk, and preservation of functional independence. CAR T-cell therapy introduces unique challenges related to cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), prolonged cytopenias, and specialized monitoring requirements. Therefore, fitness should be defined according to treatment-specific risks, expected benefit, and recovery potential rather than uniform eligibility thresholds across cellular therapies. (Farhan et al., 2025; Jayani, 2023; Mirza et al., 2025).

Table 1 summarizes a proposed assessment framework for older adults undergoing allo-HCT, autologous HCT, or CAR T-cell therapy. (Engelhardt et al., 2017; Farhan et al., 2025; Jayani, 2023; Palumbo et al., 2015).

Table 1. Proposed Multidimensional Assessment of Fitness and Frailty Before Allo-HCT, Autologous HCT, and CAR T Cell Therapy in Older Adults

Abbreviations: ADL, activities of daily living; BMI, body mass index; CAR T, chimeric antigen receptor T-cell; CHARM, Composite Health Assessment Risk Model; CFS, Clinical Frailty Scale; HCT-CI, Hematopoietic Cell Transplantation–Comorbidity Index; IADL, instrumental activities of daily living; ICANS, immune effector cell-associated neurotoxicity syndrome; IMWG, International Myeloma Working Group; MNA-SF, Mini Nutritional Assessment–Short Form; MoCA, Montreal Cognitive Assessment; SPPB, Short Physical Performance Battery.

Assessing Fitness Beyond Comorbidity in HCT

Fitness for autologous and allo-HCT has traditionally been evaluated using performance status, organ function, disease characteristics, and comorbidities. The Hematopoietic Cell Transplantation–Comorbidity Index (HCT-CI), developed by Sorror and colleagues, remains one of the most widely used instruments for pretransplant risk stratification and predicts non-relapse mortality and overall survival (Sorror et al., 2005; Sorror et al., 2014). However, the HCT-CI should be regarded as a comorbidity index rather than a comprehensive frailty instrument.

Important dimensions of vulnerability —  cognition, physical performance, sarcopenia, nutritional status, polypharmacy, falls, functional independence, psychological health, and social support — are not comprehensively represented by the HCT-CI (Jayani, 2023; Muffly et al., 2013). Consequently, a low HCT-CI does not necessarily indicate that a patient is physiologically fit, just as a higher HCT-CI should not automatically exclude a patient from transplantation.

A more comprehensive approach would integrate HCT-CI with objective functional measures such as gait speed, grip strength, SPPB, ADLs/IADLs, nutritional assessment, cognitive screening, and patient-reported physical function. This concept is particularly relevant for older adults undergoing allogeneic HCT, for whom conditioning intensity, GVHD prophylaxis, donor characteristics, disease biology, comorbidities, and physiologic reserve collectively influence outcomes (Jayani, 2023; Muffly et al., 2013). For autologous HCT, multidimensional assessment may similarly improve prediction of treatment toxicity, hospitalization, functional decline, rehabilitation requirements, and recovery (Engelhardt et al., 2017; Muffly et al., 2013; Muffly et al., 2014; Palumbo et al., 2015).

Treatment-specific assessment instruments may further refine this approach. For allogeneic HCT, the Composite Health Assessment Risk Model (CHARM) integrates conventional transplant-related risk factors with selected geriatric and clinical variables to provide additional prognostic information in older candidates. However, its predictive discrimination is modest, and it should complement rather than replace comprehensive clinical assessment (Jayani, 2023; Muffly et al., 2014).

For autologous HCT, particularly in patients with multiple myeloma, disease-specific tools, such as the International Myeloma Working Group Frailty Index and the Revised Myeloma Comorbidity Index, may help characterize vulnerability beyond ECOG performance status (Engelhardt et al., 2017; Palumbo et al., 2015). These instruments should be interpreted in the context of disease burden, treatment response, organ function, and the anticipated toxicity of high-dose therapy. Importantly, an instrument developed in one treatment population should not be automatically assumed to have equivalent predictive performance in another.

The distinction between treatment-specific fitness is especially relevant when evaluating patients aged 70 years or older. A patient with preserved functional independence but substantial cardiopulmonary comorbidity may have a different risk profile for allo-HCT than for autologous HCT. Meanwhile, a patient with limited mobility, but otherwise preserved organ function, may remain eligible for either approach after individualized assessment and optimization.

The goal is not to establish a universal definition of transplant fitness, but to determine whether the patient's physiologic reserve is sufficient for the anticipated treatment-related stressors and whether potentially reversible vulnerabilities can be addressed before proceeding (Jayani, 2023; Sorror et al., 2014).

Defining Fitness for CAR T Therapy

CAR T-cell therapy presents a distinct fitness paradigm. Unlike conventional transplantation, it does generally does not require myeloablative conditioning, and some patients who are not candidates for HCT may remain eligible for CAR T therapy. Nevertheless, treatment requires sufficient physiologic reserve to tolerate leukapheresis, bridging therapy, lymphodepletion, CRS, ICANS, infections, prolonged cytopenias, hospitalization, and potentially prolonged functional recovery (Lin et al., 2023; Mirza et al., 2025; Rejeski et al., 2023).

Prospective studies suggest that geriatric assessment can identify clinically meaningful vulnerabilities among older CAR T candidates. Lin and colleagues demonstrated the feasibility of incorporating geriatric assessment and consultation into routine CAR T evaluation (Lin et al., 2023). Subsequent experience with a multidisciplinary geriatric assessment–guided clinic showed that vulnerabilities are common and associated with increased toxicity and poorer outcomes (Yates et al., 2024).

Importantly, the purpose of frailty assessment is not to establish rigid exclusion criteria. Rather, it is intended to identify potentially modifiable vulnerabilities and guide individualized treatment planning. Functional impairment, malnutrition, polypharmacy, cognitive limitations, and inadequate caregiver support may all represent opportunities for intervention rather than barriers to treatment. (Li et al., 2021;  Yates et al., 2024; Mohile et al., 2021).

The clinically relevant question may then evolve from “Is this patient frail?” to “Which components of this patient's frailty are reversible, and does the patient retain sufficient physiologic reserve to tolerate the cellular therapy pathway?”

Identifying frailty should lead to a structured intervention strategy rather than automatically excluding an older patient from potentially beneficial treatment. Comprehensive geriatric assessment can identify potentially reversible vulnerabilities, including reduced muscle strength, impaired mobility, malnutrition, polypharmacy, cognitive difficulties, depressive symptoms, and inadequate caregiver support.

Multicomponent prehabilitation programs incorporating individualized aerobic exercise, resistance training, balance exercises, and physical therapy may improve physical performance and help patients maintain functional reserve before treatment (Jarden et al., 2009; Wiskemann et al., 2011). Nutritional interventions should address inadequate caloric and protein intake, unintentional weight loss, and sarcopenia, ideally through dietitian-guided counseling and supplementation when indicated. Medication reconciliation and pharmacist-led optimization can reduce potentially inappropriate prescribing, excessive sedative exposure, drug interactions, and medication-related functional impairment (Li et al., 2021; Mohile et al., 2021).

Additional interventions may include occupational therapy, falls prevention, cognitive and delirium-prevention strategies, management of depression and sleep disturbances, and coordinated social work or caregiver support.

However, the strength of evidence varies considerably. Randomized studies of exercise and supportive interventions in HCT populations have demonstrated feasibility and improvements in selected patient-reported or functional outcomes, but findings are heterogeneous, (Jarden et al., 2009; Wiskemann et al., 2011) and evidence that prehabilitation reduces non-relapse mortality, severe toxicity, or improves overall survival remains insufficient.

Direct evidence supporting prehabilitation specifically in adults aged 70 years or older receiving CAR T is particularly limited. Moreover, improvement in physical performance does not necessarily establish that treatment-related mortality has been reduced. Thus, these interventions should be regarded as clinically reasonable, individualized strategies for optimizing potentially modifiable vulnerabilities, while acknowledging that their ability to alter major transplant or CAR T outcomes requires confirmation in adequately powered prospective studies (Jarden et al., 2009; Li et al., 2021; Mohile et al., 2021; Wiskemann et al., 2011).

Frailty and physiologic reserve are dynamic characteristics that may change substantially during hematologic malignancy treatment. Disease control, resolution of inflammation, nutritional recovery, physical rehabilitation, and optimization of comorbidities may improve functional capacity, whereas chemotherapy toxicity, prolonged hospitalization, infections, corticosteroid exposure, and treatment-related deconditioning may accelerate functional decline (Farhan et al., 2025; Jayani, 2023). Consequently, eligibility assessment should not be restricted to a single pretreatment evaluation.

For allogeneic HCT, reassessment after induction or salvage therapy, following major hospitalization, after a defined prehabilitation period, and immediately before conditioning may identify clinically meaningful changes in transplant tolerance. For autologous HCT, repeated assessment after induction and before high-dose conditioning may help distinguish persistent frailty from treatment-related or potentially reversible impairment. In CAR T candidates, functional and geriatric reassessment is particularly relevant after bridging therapy, infection, hospitalization, or prolonged manufacturing intervals, because the patient's condition at referral may differ substantially from their status immediately before lymphodepletion.

A pragmatic longitudinal strategy would combine SPPB, gait speed, grip strength, ADL/IADL, and patient-reported physical function at baseline, immediately before treatment, and approximately days +30 and +100, followed by assessments at 6 and 12 months when feasible. These repeated measures could distinguish resilient patients who maintain function, patients experiencing transient deterioration followed by recovery, and those developing persistent functional impairment. Importantly, these trajectories may provide clinically meaningful information beyond survival alone, including the probability of maintaining independence, avoiding institutionalization, and returning to baseline activities (Farhan et al., 2025; Jarden et al., 2009; Wiskemann et al., 2011).

Future prospective studies should determine whether changes in frailty and physical performance following prehabilitation or treatment optimization predict subsequent toxicity, non-relapse mortality, quality of life, and survival, and whether incorporating dynamic assessments improves treatment selection beyond conventional baseline risk models (Farhan et al., 2025; Jarden et al., 2009; Wiskemann et al., 2011).

Prospective studies are still needed to establish standardized CAR T fitness criteria and determine how frailty should influence patient selection, prehabilitation, toxicity prevention, supportive care, and post-treatment rehabilitation. Integration of clinical frailty assessment with inflammatory biomarkers, immune fitness, immunosenescence, sarcopenia, and CAR T cellular kinetics represents an especially promising area for translational investigation. Likewise, future fitness measures may be combined with validated toxicity prediction scores to better anticipate treatment tolerability and inform supportive care strategies (Rejeski et al., 2023). However, T-cell differentiation, exhaustion, senescence, and metabolic fitness remain investigational biomarkers and should not currently be used as standalone criteria for excluding older patients from CAR T therapy.

Frailty-Directed Interventions Across Cellular Therapies

Identification of frailty should prompt a structured evaluation of potentially modifiable vulnerabilities rather than automatic exclusion from treatment. Across autologous HCT, allogeneic HCT, and CAR T-cell therapy, geriatric assessment can identify deficits that may be amenable to intervention before treatment (Farhan et al., 2025; Jayani, 2023; Mohile et al., 2021). Common targets for intervention include:

• Physical impairment and deconditioning
• Malnutrition and sarcopenia
• Polypharmacy and medication-related toxicity
• Cognitive and psychological health
• Comorbid disease burden
• Social and caregiver support needs

Interventions should be individualized according to the deficits identified through geriatric and functional assessment. Patients with reduced gait speed, impaired balance, or low SPPB scores may benefit from supervised physical therapy, progressive resistance training, aerobic conditioning, and fall-prevention strategies. Nutritional optimization should address inadequate protein and caloric intake, unintentional weight loss, and treatment-related gastrointestinal symptoms, ideally through early dietitian involvement. Medication reconciliation, renal dose adjustment, management of neuropathy and pain, and optimization of cardiovascular and metabolic comorbidities may further improve treatment readiness.

In selected patients, a short prehabilitation period between induction therapy and high-dose conditioning may provide an opportunity to improve physical reserve without compromising disease control. Evidence from exercise and rehabilitation studies in HCT populations suggests potential benefits for physical performance, fatigue, and quality of life, although studies specifically evaluating frail older auto-HCT recipients remain limited. Importantly, there is insufficient evidence that prehabilitation independently reduces day-100, non-relapse mortality, severe treatment toxicity, or improves overall survival. Therefore, frailty-directed interventions should currently be considered strategies to improve functional readiness and recovery rather than validated methods for reducing transplant-related mortality.

Frailty-directed optimization before allo-HCT is particularly important because patients face the combined physiologic burden of conditioning chemotherapy, prolonged immunosuppression, infectious complications, graft-versus-host disease (GVHD), and potentially extended functional recovery. A multidimensional geriatric assessment can identify actionable vulnerabilities that are not adequately captured by HCT-CI or conventional performance status.

Patients with impaired physical function may benefit from individualized prehabilitation programs incorporating resistance exercises, aerobic training, balance rehabilitation, and physical therapy before conditioning, with continuation during hospitalization and after transplantation when clinically feasible. Nutritional interventions should address sarcopenia, inadequate oral intake, weight loss, and micronutrient deficiencies, while pharmacist-led medication review may reduce potentially inappropriate medications, sedative exposure, drug interactions, and treatment-related complications. Additional interventions include cognitive screening, delirium-prevention strategies, psychosocial support, caregiver education, and optimization of cardiopulmonary and other chronic conditions.

Compared with CAR T therapy, allo-HCT has a more established interventional evidence base. Randomized studies by Wiskemann and colleagues and Jarden and colleagues demonstrated that structured exercise or multimodal interventions around allogeneic transplantation can improve selected measures of physical capacity, fatigue, functional performance, and quality of life, although results vary across outcomes and studies (Jarden et al., 2009; Wiskermann et al., 2011).

Nevertheless, these studies were not designed specifically to establish that reversing frailty reduces non-relapse mortality, severe GVHD, relapse, or overall mortality in adults aged 70 years or older. Accordingly, prehabilitation and geriatric optimization are reasonable components of supportive care, but their effects on major transplant outcomes require confirmation in prospective trials incorporating standardized frailty measurements and clinically meaningful endpoints.

Frailty-directed interventions before CAR T therapy should account for the distinctive treatment pathway, including leukapheresis, bridging therapy, lymphodepletion, acute immune-mediated toxicities, and potentially prolonged cytopenias and functional recovery. Unlike allogeneic HCT, the primary challenge is not tolerance of myeloablative conditioning or GVHD, but rather the ability to withstand CRS, ICANS, infections, hospitalization, and treatment-related deconditioning. A geriatric assessment-guided approach can identify potentially modifiable vulnerabilities and direct individualized interventions.

Patients with impaired mobility, reduced muscle strength, or a history of falls may benefit from physical therapy, progressive resistance exercises, and balance training; those with weight loss, inadequate oral intake, or sarcopenia should receive early nutritional assessment and targeted dietary support. Medication optimization is particularly relevant for patients receiving sedatives, anticholinergic medications, or other neuroactive agents that may complicate neurologic assessment or increase delirium risk. Baseline cognitive impairment should prompt delirium-prevention strategies, caregiver education, and enhanced neurologic monitoring rather than automatic exclusion. Because bridging therapy, infections, and hospitalization may substantially alter physiologic reserve, functional status should be reassessed before lymphodepletion. The evidence supporting this approach is promising but remains largely observational.

In a geriatric assessment-guided multidisciplinary clinic study involving 61 older CAR T candidates, 53 subsequently received CAR T therapy; patients recommended to proceed had lower intensive care utilization and better overall survival than those advised against treatment (Yates et al., 2024). However, these findings do not establish that geriatric interventions themselves caused the improved outcomes, because baseline vulnerability, patient selection, and disease-related factors may have contributed (Yates et al., 2024).

Toward Individualized Fitness Assessment

Frailty assessment is evolving into an essential component of patient evaluation for HCT and CAR T-cell therapy. HCT-CI remains valuable for quantifying comorbidity and predicting transplant-related risk, but HCT-CI should not be considered synonymous with frailty assessment (Sorror et al., 2005). Multidimensional assessment provides additional information regarding physical function, cognition, nutrition, medications, psychosocial factors, and physiologic reserve (Jayani, 2023; Muffly et al., 2013; Muffly et al., 2014).

Importantly, the concept of fitness should be tailored to the specific demands of allogeneic HCT, autologous HCT, and CAR T therapy. Allo-HCT requires consideration of conditioning toxicity, GVHD, prolonged immunosuppression, and non-relapse mortality; autologous HCT emphasizes tolerance of high-dose chemotherapy, hematologic recovery, and preservation of functional independence; and CAR T therapy introduces distinct risks associated with CRS, ICANS, infections, prolonged cytopenias, and immune effector cell function.

Across all three modalities, frailty should be regarded as a potentially dynamic and partially modifiable state rather than a fixed characteristic established at the initial consultation. Systematic reassessment following induction or bridging therapy, hospitalization, prehabilitation, and immediately before treatment may provide more clinically meaningful information than a single baseline evaluation (Farhan et al., 2025; Jarden et al., 2009; Jayani, 2023; Wiskemann et al., 2011).

For CAR T therapy, standardized definitions of fitness and frailty remain an important unmet need (Lin et al., 2023; Yates et al., 2024; Munshi et al., 2025). Future prospective studies should integrate frailty, objective physical performance, comorbidity, cognition, nutrition, sarcopenia, patient-reported outcomes, inflammatory and immune biomarkers, and treatment-specific outcomes. Equally important, interventional studies are needed to determine whether targeted prehabilitation, nutritional optimization, medication review, rehabilitation, and multidisciplinary supportive care can improve treatment tolerance, functional recovery, quality of life, and survival (Jarden et al., 2009; Li et al., 2021; Mohile et al., 2021; Wiskemann et al., 2011).

Ultimately, the objective should not be to establish an arbitrary threshold defining “how frail is too frail.” Instead, clinicians should identify treatment-specific vulnerabilities, distinguish potentially reversible vulnerability from treatment futility, implement targeted interventions when appropriate.

Future studies should define standardized fitness criteria, validate dynamic assessment strategies, and determine whether prehabilitation, nutritional optimization, medication review, and multidisciplinary supportive care can improve treatment tolerance, functional recovery, quality of life, and survival. By moving beyond frailty identification toward individualized optimization, HCT and cellular therapy programs may improve both access to treatment and outcomes for older adults receiving allogeneic HCT, autologous HCT, and CAR T-cell therapy.

References

1. Jayani RV. How old is too old? Frailty and geriatric assessments of older patients undergoing allogeneic HCT. Hematology Am Soc Hematol Educ Program. 2023;2023(1):709-714. doi:10.1182/hematology.2023000457.

2. Muffly LS, Kocherginsky M, Stock W, et al. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica. 2014;99(8):1373-1379. doi:10.3324/haematol.2014.103655.

3. Muffly LS, Boulukos M, Swanson K, et al. Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients. Biol Blood Marrow Transplant. 2013;19(3):429-434. doi:10.1016/j.bbmt.2012.11.006.

4. Munshi PN, Olin RL, Wall S, McCurdy SR, Al-Juhaishi T, Baker J, Bhatt VR, Chokr N, Dahi P, DeFilipp Z, Espinoza-Gutarra M, Farhan S, Gowda L, Hamilton BK, Inamoto Y, Jayani R, Kharfan-Dabaja MA, Lin R, Meyers G, Mishra A, Murthy HS, Nawas M, Rosko AE, Ruiz M, Sorror ML, Sung AD, Carpenter PA, Hamadani M, Artz AS. US Geriatric Assessment Practices for Older Adults Undergoing Hematopoietic Cell Transplantation or Chimeric Antigen Receptor T Cell Therapy: An American Society for Transplantation and Cellular Therapy Physician Survey from the Aging Special Interest Group and Committee on Practice Guidelines. Transplant Cell Ther. 2025 May;31(5):285-296. doi: 10.1016/j.jtct.2025.02.014. Epub 2025 Feb 15. PMID: 39961473.

5. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-2919. doi:10.1182/blood-2005-05-2004.

6. Lin RJ, Kim SJ, Brown S, et al. Prospective geriatric assessment and geriatric consultation in CAR T-cell therapy for older patients with lymphoma. Blood Adv. 2023;7(14):3501-3505. doi:10.1182/bloodadvances.2023010003.

7. Yates SJ, Cursio JF, Artz A, Kordas K, Bishop MR, Derman BA, Kosuri S, Riedell PA, Kline J, Jakubowiak A, Mortel M, Johnson S, Nawas MT. Optimization of older adults by a geriatric assessment-guided multidisciplinary clinic before CAR T-cell therapy. Blood Adv. 2024 Jul 23;8(14):3785-3797. doi: 10.1182/bloodadvances.2024012727. PMID: 38810262; PMCID: PMC11298834.

8. Mirza AS, Hosing C, Foss F, Kim S, Moskop A, Oloyede T, Abid MB, Afrough A, Ahmed S, Badar T, Barba P, Bhatt VR, Brown VI, Dahiya S, Deol A, Epperla N, Ganguly S, Grover NS, Hashmi H, Hashmi S, Hematti P, Hildebrandt GC, Hill JM Jr, Hossain NM, Ibrahim U, Johnson PC, Kharfan-Dabaja MA, Krem MM, Lekakis LJ, Maziarz RT, Murthy HS, Riedell PA, Salas MQ, Shouse G, Strouse C, Thakar MS, Turtle CJ, Woolfrey A, Wudhikarn K, Yared JA, Pasquini MC, Gowda L. Impact of age on outcomes after CD19 CAR T-cell therapy for large B-cell lymphomas. Blood Neoplasia. 2025 Nov 25;3(2):100187. doi: 10.1016/j.bneo.2025.100187. PMID: 41867486; PMCID: PMC12999346.

9. Farhan S, Kennedy VE, Espinoza-Gutarra MR, Lust H, Bobillo MSO, Lin AY, Olin RL, Lin RJ, Rentscher KE, Taylor MR, Mohanraj L, Wood WA, Murthy HS, Ahmed N, Dueck AC, Phelan R, Kelly DL, Yuen C, Munshi PN, Schoemans H, Hamilton BK, Lee C, Sung AD. Assessing physical function in transplantation and CAR-T recipients: expert recommendations from the survivorship, aging and biobehavioral special interest groups of ASTCT. Transplant Cell Ther. 2025 Oct;31(10):742-755. doi: 10.1016/j.jtct.2025.06.017. Epub 2025 Jun 20. PMID: 40545000; PMCID: PMC13189036.

10. Rejeski K, Hansen DK, Bansal R, Sesques P, Ailawadhi S, Logue JM, Bräunlein E, Cordas Dos Santos DM, Freeman CL, Alsina M, Theurich S, Wang Y, Krackhardt AM, Locke FL, Bachy E, Jain MD, Lin Y, Subklewe M. The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma. J Hematol Oncol. 2023 Jul 31;16(1):88. doi: 10.1186/s13045-023-01465-x. PMID: 37525244; PMCID: PMC10391746.

11. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125(13):2068-2074. doi:10.1182/blood-2014-12-615187.

12. Engelhardt M, Domm AS, Dold SM, Ihorst G, Reinhardt H, Zober A, et al. A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients. Haematologica. 2017;102(5):910-921. doi:10.3324/haematol.2016.162693.

13. Sorror ML, Storer BE, Sandmaier BM, Maloney DG, Chauncey TR, Langston A, et al. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol. 2014;32(29):3249-3256. doi:10.1200/JCO.2013.53.8157.

14. Wiskemann J, Dreger P, Schwerdtfeger R, Bondong A, Huber G, Kleindienst N, et al. Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Blood. 2011;117(9):2604-2613. doi:10.1182/blood-2010-09-306308.

15. Jarden M, Baadsgaard MT, Hovgaard DJ, Boesen E, Adamsen L. A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT. Bone Marrow Transplant. 2009;43(9):725-737. doi:10.1038/bmt.2009.27.

16. Mohile SG, Mohamed MR, Xu H, Culakova E, Loh KP, Magnuson A, et al. Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study. Lancet. 2021;398(10314):1894-1904. doi:10.1016/S0140-6736(21)01789-X.

17. Li D, Sun CL, Kim H, et al. Geriatric assessment-driven interventions (GAIN) on chemotherapy related toxic effects in Older adults with Cancer: A Randomized Clinical trial to improve treatment outcomes in older adults with cancer: evidence and implementation considerations. Randomized clinical trial. JAMA Oncol 2021. Nov 1; 7: e214158 doi: 10.1001/jamaoncol.2021.4158. Epub 2021 Nov 18.

Marco Ruiz, MD, MPH, MSc, MBA

Marco Ruiz, MD, MPH, MSc, MBA is a professor of medicine in the Department of Oncology at Florida International University (FIU) College of Medicine and program director of the Hematology/Oncology Fellowship at FIU/Baptist Health in Miami, Florida. Dr. Ruiz is  a hematologist-oncologist and blood and marrow transplant physician at the Miami Cancer Institute at Baptist Health South Florida. For more than 20 years, he has specialized in the care of patients with hematologic malignancies, particularly multiple myeloma, as well as blood and marrow transplantation and CAR T-cell therapy. His research interests include multiple myeloma, malignancies in patients with HIV, and the role of geriatric assessment in transplantation and cellular therapy. He serves as co-chair of ASTCT’s Committee on Education and Content and is a member of the ASTCT Aging Special Interest Group Steering Committee.

Marc J. Braunstein, MD, PhD, FACP, FASCO

Marc J. Braunstein, MD, PhD, FACP, FASCO, is an associate professor of medicine at NYU Grossman Long Island School of Medicine and program director of the Hematology/Oncology Fellowship at NYU Langone Health–Long Island. A board-certified hematologist-oncologist and physician-scientist, Dr. Braunstein specializes in plasma cell disorders, particularly multiple myeloma, as well as B-cell malignancies and hematopoietic stem cell transplantation. He co-directs the Autologous Stem Cell Transplantation Program and has helped expand access to cellular therapies on Long Island. His academic interests include clinical and translational research, immunotherapy, stem cell transplantation, and clinical trials in multiple myeloma and lymphoma. He serves as vice chair of ASTCT’s Committee on Education and Content and is committed to advancing medical education and mentorship within the field.