Orthostatic hypotension is classically defined as a decrease in systolic blood pressure of at least 20 millimeters of mercury, or a decrease in diastolic pressure of at least 10 millimeters of mercury, upon standing. In healthy people, standing triggers an almost instantaneous cascade of physiological responses: baroreceptors in the carotid arteries and aortic arch sense the pooling of blood in the legs and abdomen, prompting a reflexive increase in heart rate and constriction of blood vessels to maintain cerebral perfusion. When this autonomic compensation falters, the brain is briefly starved of oxygenated blood, producing lightheadedness, visual dimming, or in severe cases, fainting. While some patients remain entirely asymptomatic despite meeting the diagnostic criteria, others report fatigue, difficulty concentrating, or neck discomfort. In the general population, the condition is associated with falls, substantial morbidity, and even increased mortality, making its presence in vulnerable cancer patients a genuine safety concern.

The study cohort comprised 153 patients undergoing autologous hematopoietic cell transplantation, 127 receiving allogeneic transplants, and 17 treated with chimeric antigen receptor T-cell, or CAR-T, therapy. Blood pressure and heart rate were measured while patients lay supine and again at one and three minutes after standing, following institutional protocol. When the researchers stratified results by therapy type, the cumulative incidence of any orthostatic hypotension at day 30 was 62.8 percent in the autologous group, 52.0 percent in the allogeneic group, and 52.9 percent in the CAR-T group, a difference that did not reach statistical significance. However, the timing of onset varied subtly between groups. CAR-T patients tended to develop the condition earliest, with a median onset of day one, compared with day four in allogeneic recipients and day five in autologous transplant patients. Symptomatic disease was significantly more frequent in the autologous group, affecting 28.8 percent, compared with 15.7 percent of allogeneic patients and 5.9 percent of CAR-T recipients.

The early onset in CAR-T patients offers a tantalizing clue about underlying biology. CAR-T therapy works by engineering a patient’s own T cells to attack cancer, but the treatment frequently unleashes a flood of inflammatory signaling molecules known as cytokines. These molecules can drive hypotension by increasing the permeability of blood vessel walls, allowing fluid to leak out of the circulation and reducing the effective circulating blood volume. Elevated levels of cytokines such as interleukin-6, tumor necrosis factor-alpha, and transforming growth factor-alpha, which are common in patients with advanced malignancy, have also been correlated with disrupted circadian regulation and cortisol rhythms, implying impaired autonomic control of the cardiovascular system. In transplant patients, additional mechanisms come into play, including chemotherapy-induced gastrointestinal mucositis, nausea, and reduced oral intake, all of which deplete intravascular volume, alongside diarrhea, electrolyte disturbances, and medications with autonomic side effects.

Perhaps the most provocative finding concerned the care setting. Among patients with plasma cell disorders who underwent autologous transplantation, the researchers compared 96 inpatients with 19 outpatients treated more recently. The incidence of orthostatic hypotension was dramatically higher in the outpatient group, reaching 94.7 percent by day 30 compared with 54.2 percent among hospitalized patients, and onset occurred significantly earlier, at a median of day four versus day six. For symptomatic disease, the gap was even wider: 63.2 percent of outpatients versus 22.9 percent of inpatients. In multivariate analysis, outpatient treatment emerged as the strongest risk factor, carrying a hazard ratio of 3.60 for any orthostatic hypotension and 4.66 for the symptomatic form. The authors suggest this may reflect less fluid intake and poorer nutritional status on the patient side, combined with less intensive monitoring and fluid management on the provider side, though they caution that the small outpatient sample and differences in blood pressure monitoring may partly explain the disparity.

Beyond care setting, the analysis identified several other independent risk factors. A documented history of orthostatic hypotension before cellular therapy increased the risk of developing the condition again, with a hazard ratio of 1.76. For symptomatic disease, weight loss exceeding 2 percent from baseline roughly doubled the risk, with a hazard ratio of 2.09, while the occurrence of any infection within the first 30 days raised the risk by a factor of 2.57. The infection finding is particularly novel; the authors report that this is the first study to describe infection as a potential risk factor for orthostatic hypotension in the cancer population, with neutropenic fever being the most frequent infectious event in the cohort. Infections can precipitate distributive hypovolemia and vasodilation, undermining the very mechanisms the body relies upon to maintain blood pressure when standing. The weight loss threshold of 2 percent was chosen because losses of that magnitude are generally recognized as an indicator of dehydration.

Intriguingly, the analysis produced one result that runs counter to established expectations. Older patients, defined as those aged 60 and above, and male patients appeared to have a lower risk of developing symptomatic orthostatic hypotension, with hazard ratios of 0.38 and 0.56 respectively. Because aging is normally associated with an increased risk of the condition, the researchers interpret this apparent protective effect with considerable caution. They suggest it most likely reflects bias rather than biology: older adults often have diminished awareness of symptoms related to reduced cerebral blood flow and may report falls rather than typical complaints such as dizziness, while retrospective designs introduce ascertainment and detection biases. Older patients may also have been less likely to receive outpatient therapy, which was itself the strongest risk factor. The authors label this observation hypothesis-generating and call for prospective confirmation.

Notably, the occurrence of orthostatic hypotension did not translate into measurable differences in hard clinical outcomes. Among the 278 hospitalized patients, there were no statistically significant differences between those who did and did not develop the condition in relapse rates, non-relapse mortality, or overall survival at 100 days and one year. The study also found no significant association between orthostatic hypotension and fall events, though only ten falls occurred across the entire cohort, leaving the analysis underpowered to detect such a link. Nine of the ten patients who fell had experienced weight loss exceeding 2 percent before or shortly after the fall, and routine interventions, including bed-exit alarms for inpatients and fluid supplementation for affected patients, may have suppressed fall rates even among those with the condition. The absence of statistical significance, the authors emphasize, should not be read as evidence of no association.

The practical implications of the study are straightforward and potentially transformative for supportive care in hematology. The researchers recommend incorporating active orthostatic vital sign measurement, meaning supine and standing blood pressure and heart rate, into routine assessment during and after cellular therapy, ideally at least daily during the highest-risk early post-infusion period and at every outpatient visit. Patients found to have orthostatic hypotension can be managed with a stepwise approach that includes reviewing and, where appropriate, temporarily reducing antihypertensive medications, oral or intravenous fluid repletion guided by daily weights, patient education about slow positional changes and adequate fluid and salt intake, and fall prevention measures. Those with symptomatic or recurrent episodes, or patients being managed as outpatients, may warrant closer monitoring and a lower threshold for preemptive fluid support. These recommendations align with current cardio-oncology guidance from the American Heart Association and European Society of Cardiology on recognizing and managing autonomic dysfunction in patients with cancer. As cellular therapies continue to expand into new cancers and earlier lines of treatment, the humble blood pressure cuff may prove to be one of the most important tools in protecting patients through their recovery.

Subject of Research: Orthostatic hypotension incidence and risk factors in patients receiving hematopoietic cell transplantation and CAR-T cellular therapy

Article Title: Unmasking orthostatic hypotension after cellular therapy: risk factors, implications, and clinical significance

Article References: Vazquez-Urrutia, J. R., Santucci, J., Modgil, P., Lal, A., Inoue, Y., Zimmerman, J., Woodworth, R., Knol, K., Hess, E., Jordan, J., Stover, J., Rekawek, E., Cioccio, J., Rakszawski, K., Songdej, N., Nickolich, M., Zheng, H., Naik, S., Ehmann, C., … Minagawa, K. (2026). Unmasking orthostatic hypotension after cellular therapy: risk factors, implications, and clinical significance. Supportive Care in Cancer, 34(10), Article 1023. https://doi.org/10.1007/s00520-026-11247-z

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11247-z

Keywords: orthostatic hypotension, cellular therapy, hematopoietic cell transplantation, CAR-T therapy, blood pressure, falls, weight loss, infection, outpatient care, supportive care, autonomic dysfunction, oncology

Falls are far more than an inconvenient stumble. They are a leading cause of injury, disability, loss of independence and death among older people worldwide. A fall can trigger a cascade of adverse outcomes: fractures, particularly of the hip, hospitalization, fear of falling again, reduced mobility, social isolation and, ultimately, admission to long-term care. Landmark work has demonstrated that falls and fall-related injuries significantly elevate the risk of nursing home admission, while more recent studies have linked falls to accelerated cognitive decline and dementia, and emergency services data show that older adults who fall face elevated mortality and heavy healthcare utilization in the year that follows. Mortality from falls among the oldest adults has been rising in several countries, and the World Guidelines for Falls Prevention and Management, published in 2022 as a global initiative, have emphasized that falls should be treated as a major, modifiable public health problem rather than an inevitable accompaniment of ageing. The new Irish findings give that warning renewed urgency, because they show that a high-income country with an established research infrastructure and clinical awareness of falls is nonetheless seeing the problem grow.

The study, published in European Geriatric Medicine, was conducted by a team from The Irish Longitudinal Study on Ageing at Trinity College Dublin, the Mercer’s Institute for Successful Ageing at St James’s Hospital, and the Royal College of Surgeons in Ireland, led by Kate Doyle and colleagues including Robert Briggs, Rose-Anne Kenny, Frank Moriarty, Amanda Lavan, Siobhan Scarlett and Caoimhe McGarvey. Rather than relying on a single snapshot, the investigators harnessed the longitudinal design of TILDA, a nationally representative cohort that has followed thousands of older Irish adults with detailed health assessments since 2009. The analysis focused on three time points separated by years: Wave 1, carried out between 2009 and 2011 and including 3,507 participants aged 65 or over with a mean age of 73.3 years; Wave 3, conducted between 2014 and 2015 with 3,582 participants of mean age 73.9; and Wave 6, completed between 2021 and 2023 with 3,333 participants whose mean age was 74.3. Women made up slightly more than half of each sample, a proportion that rose modestly from 52.5 percent at Wave 1 to 55.3 percent at Wave 6.

The conceptual heart of the study lies in its focus on modifiable falls risk factors, the concrete, measurable and potentially reversible conditions that clinical guidelines recommend assessing in anyone at high risk of falling. Three domains took center stage. The first was the use of fall-risk-increasing drugs, abbreviated FRIDs, a class of medications identified through a validated instrument known as the Screening Tool of Older Persons Prescriptions in older adults with high fall risk, or STOPPFall. This tool, developed by a European task force on fall-risk-increasing drugs, catalogues medications whose pharmacological actions can precipitate a fall: sedatives and hypnotics that dull arousal and slow reactions, antidepressants that affect balance and blood pressure regulation, antipsychotics, benzodiazepines, opioids, antihypertensives and other agents that can induce dizziness, orthostatic drops in blood pressure, or impaired cognition. Because FRIDs are prescribed, they are in principle directly modifiable through deprescribing and medication review, which is precisely why the research team prioritized tracking them over time.

The second risk factor was orthostatic hypotension, a phenomenon in which blood pressure falls abnormally upon standing, depriving the brain of perfusion and producing dizziness, unsteadiness or frank syncope. In this analysis, orthostatic hypotension was operationalized in a way that captures both the objective hemodynamic measure and the symptomatic experience: a drop in systolic blood pressure of at least 20 millimeters of mercury upon standing from sitting, and/or self-reported orthostatic unsteadiness. This dual definition matters clinically, because research from the TILDA cohort itself has shown that even asymptomatic orthostatic hypotension, detected only on measurement, predicts future falls, and that delayed blood pressure recovery after standing independently predicts fracture in community-dwelling older people. Systematic reviews and meta-analyses confirm that orthostatic hypotension is associated with a substantially elevated risk of falls, and that drug-related causes extend well beyond antihypertensive medications to include antidepressants, dopaminergic agents and other drug classes. The third domain was mobility impairment, quantified using the Timed Up-and-Go test, or TUG, a simple but well-validated performance measure in which an individual rises from a chair, walks three meters, turns, returns and sits down again. A completion time of 12 seconds or longer was classified as mobility impairment. Decades of research have established that TUG times above this threshold predict falls with useful accuracy, reflecting underlying deficits in gait, balance, muscle power and executive function.

The results concerning these risk factors were strikingly consistent and consistently concerning. At every one of the three waves, more than one in four older Irish adults was taking at least one medication flagged by the STOPPFall criteria, and more than one in seven was taking two or more such drugs. More than one in five of the population met the definition of orthostatic hypotension at each assessment. More than one in four had mobility impairment on the Timed Up-and-Go test. These proportions did not fluctuate dramatically between 2009 and 2023; instead, they formed a stable, elevated plateau of risk factors threading through the entire period. The stability is itself the message: the underlying physiological and pharmacological conditions that make older people prone to falling were pervasive throughout the fifteen-year window, and the rising incidence of falls occurred against this unchanging backdrop of hazard. The combination also paints a mechanistic picture, in which sedating and blood-pressure-lowering medications compromise cardiovascular and neurological resilience, orthostatic hypotension undermines the body’s ability to maintain cerebral perfusion during postural change, and impaired mobility reduces the margin of safety in everyday movement, with their overlap amplifying individual vulnerability.

Weighting the data to reflect the national population sharpened the implications. The rise from 22.1 percent to 29.8 percent in fall incidence corresponds to an increase from roughly 117,665 affected individuals to approximately 228,007, an expansion driven by both a higher rate of falling per person and the growth of the older population itself, as documented in the 2022 Irish census. Each fall carries costs that ripple outward through emergency departments, orthopedic services, rehabilitation units, primary care and family caregiving. Prior TILDA-based research has shown that older people’s use of emergency departments surged even during the COVID-19 pandemic, and fall-related injuries are among the most common reasons older adults require acute care. If roughly three in ten older adults now experience falls in a given period, the arithmetic of an ageing society ensures that absolute numbers of fall-related fractures, head injuries and deaths will continue to climb unless the underlying trajectory changes. The authors argue that this constitutes a clear case for population-level action: falls risk factors, because they are common, modifiable and measurable, are legitimate targets for national falls prevention policy, not merely for individual clinical assessment.

The study also carries practical lessons for how such prevention might work. Multifactorial interventions, which combine medication review, exercise, management of orthostatic hypotension, vision correction and environmental modification, have demonstrated effectiveness in preventing falls among community-dwelling older adults in systematic reviews and meta-analyses. The STOPPFall framework offers clinicians a structured pathway for identifying and, where appropriate, deprescribing fall-risk-increasing drugs, and recent work from specialist falls and syncope services shows that such reviews are feasible in practice and can reshape prescribing patterns. Timed Up-and-Go screening can be administered in primary care with minimal equipment, and orthostatic blood pressure measurement is inexpensive and quick, yet both remain underused outside specialist settings. The Irish findings suggest that screening for these three conditions at a population scale, followed by targeted intervention, represents one of the most concrete available strategies to bend the curve of falls incidence. International guidelines echo this position, calling for health systems to embed falls risk assessment and management into routine care for older adults.

Ultimately, the study is a reminder that scientific progress and public health outcomes are not the same thing. Ireland possesses one of the world’s richest longitudinal datasets on ageing, its researchers have contributed decisively to the global understanding of falls, syncope, medication risk and mobility in later life, and the clinical tools for prevention are validated and available. Yet the incidence of falls has risen from roughly one in five older adults to nearly one in three over the span of the study, and the prevalence of fall-risk-increasing drug use, orthostatic hypotension and mobility impairment has remained stubbornly high throughout. The researchers conclude that addressing falls risk factors must become a priority of national falls prevention policy at the population level, so that the burden of falls and fall-related injuries can be reduced before demographic ageing multiplies it further. For a rapidly ageing world watching closely how societies adapt to longer lives, the Irish data offer both a warning and a blueprint: the components of prevention are known, but they must now be deployed at scale.

Subject of Research: Longitudinal trends in falls incidence and modifiable falls risk factors among community-dwelling older adults in Ireland

Article Title: Longitudinal trends in the incidence of falls and prevalence of risk factors for falls in community-dwelling older people in Ireland

Article References: Doyle, K., McGarvey, C., Scarlett, S., Moriarty, F., Lavan, A., Kenny, R.-A., & Briggs, R. (2026). Longitudinal trends in the incidence of falls and prevalence of risk factors for falls in community-dwelling older people in Ireland. European Geriatric Medicine. https://doi.org/10.1007/s41999-026-01602-y

Image Credits: AI Generated

DOI: 10.1007/s41999-026-01602-y

Keywords: falls, older people, community-dwelling, fall-risk-increasing drugs, STOPPFall, orthostatic hypotension, Timed Up-and-Go, mobility impairment, TILDA, ageing, epidemiology, falls prevention