Prospective neurocognitive function over 5 years after allogeneic hematopoietic cell transplantation for cancer survivors compared with matched controls at 5 years.

PURPOSE: Research has documented cognitive deficits both before and after high-dose treatment followed by allogeneic hematopoietic cell transplantation (HCT), with partial recovery by 1 year. This study prospectively examined the trajectory and extent of long-term cognitive dysfunction, with a focus on 1 to 5 years after treatment. PATIENTS AND METHODS: Allogeneic HCT recipients completed standardized neuropsychological tests including information processing speed (Trail Making A and Digit Symbol Substitution Test), verbal memory (Hopkins Verbal Learning Test-Revised), executive function (Controlled Oral Word Association Test and Trail Making B), and motor dexterity and speed (Grooved Pegboard). Survivors (n = 92) were retested after 80 days and 1 and 5 years after transplantation. Case-matched controls (n = 66) received testing at the 5-year time point. A Global Deficit Score (GDS) summarized overall impairment. Response profiles were analyzed using linear mixed effects models. RESULTS: Survivors recovered significant cognitive function from post-transplantation (80 days) to 5 years in all tests (P < .0001) except verbal recall (P > .06). Between 1 and 5 years, verbal fluency improved (P = .0002), as did executive function (P < .01), but motor dexterity did not (P > .15), remaining below controls (P < .0001) and more than 0.5 standard deviation below population norms. In GDS, 41.5% of survivors and 19.7% of controls had mild or greater deficits (NcNemar test = 7.04, P = .007). CONCLUSION: Although neurocognitive function improved from 1 to 5 years after HCT, deficits remained for more than 40% of survivors. Risk factors, mechanisms and rehabilitation strategies need to be identified for these residual deficits.

Pre- and post-transplantation risk factors for delirium onset and severity in patients undergoing hematopoietic stem-cell transplantation.

PURPOSE: To determine pre- and post-transplantation risk factors for delirium onset and severity during the acute phase of myeloablative hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Ninety adult patients with malignancies admitted to the Fred Hutchinson Cancer Research Center for their first HSCT were assessed prospectively from 1 week before transplantation to 30 days after transplantation. Delirium was assessed three times per week using the Delirium Rating Scale and the Memorial Delirium Assessment Scale. Potential risk factors were assessed by patient self-report, charts, and computerized records. Multivariable analysis of time to onset of a delirium episode was undertaken using Cox proportional hazards regression with time-varying covariates. Analysis for delirium severity was carried out using a linear mixed effects model. Validation and sensitivity analyses were performed on the final models. RESULTS: Forty-five patients (50%) experienced a delirium episode. Pretransplantation risk factors for onset and higher severity of delirium were higher mean alkaline phosphatase and blood urea nitrogen (BUN) levels. Poorer pretransplantation executive functioning was also associated with higher delirium severity. Higher doses of opioid medications were the only post-transplantation risk factor for delirium onset (hazard ratio, 1.05; 95% CI, 1.02 to 1.08). Higher opioid doses, current and prior pain, and higher BUN levels were post-transplantation risk factors for greater delirium severity (all P < .01). CONCLUSION: Pre- and post-transplantation factors can assist in identifying patients who are at risk for delirium during myeloablative HSCT and may enable clinical interventions to prevent delirium onset or decrease delirium symptoms.

Impact of delirium on decision-making capacity after hematopoietic stem-cell transplantation.

BACKGROUND: Delirium is a common complication of myeloablative hematopoietic stem-cell transplantation (HSCT), yet no studies have explored the later effects of an episode of delirium in this setting on patients' decision-making capacity after the acute symptoms of delirium have resolved. OBJECTIVE: The authors assessed the impact of delirium during the acute phase of myeloablative HSCT on later decision-making capacity. METHOD: Decision-making capacity was assessed with the MacArthur Competence Assessment Tool in 19 patients before they received their first HSCT and at 30 and 80 days post-transplantation. Delirium was assessed 3 times per week with the Delirium Rating Scale and the Memorial Delirium Assessment Scale from 7 days pre-transplantation through 30 days post-transplantation. RESULTS: Although there was little variance in the pre-treatment scores, with most patients showing very high or perfect scores on decision-making abilities, a multivariate regression model showed that delirium was predictive of a lower reasoning score at Day 30 post-transplantation. CONCLUSION: Patients who experienced a delirium episode during the acute phase of HSCT were not likely to develop clinically meaningful impairments in decision-making capacity post-transplantation, although they evidenced minor impairment in their reasoning ability.

Impact of delirium on cognition, distress, and health-related quality of life after hematopoietic stem-cell transplantation.

PURPOSE: To determine the impact of delirium during the acute phase of myeloablative hematopoietic stem-cell transplantation (HSCT) on health-related quality of life (HRQOL), distress, and neurocognitive functioning 30 and 80 days after transplantation. PATIENTS AND METHODS: Ninety patients completed a battery assessing HRQOL, distress, and neuropsychological functioning before receiving their first HSCT. Delirium was assessed three times per week using the Delirium Rating Scale and the Memorial Delirium Assessment Scale from 7 days before transplantation through 30 days after transplantation. At 30 days after transplantation, distress and neurocognitive functioning were assessed. At 80 days after transplantation, HRQOL, distress, and neuropsychological functioning were re-evaluated. RESULTS: After adjusting for confounding factors, patients who experienced a delirium episode, versus patients who did not, reported significantly worse depression, anxiety, and fatigue symptoms at 30 days (linear regression beta(s) = 0.2, 0.3, and 0.5, respectively; P < .04). At 80 days, patients with a delirium episode had significantly worse executive functioning (beta = -1.1; P < .02), attention and processing speed (beta(s) = -4.7 and -5.4, respectively; P < .03), mental health on the Medical Outcomes Study Health Survey, 12-item short form (beta = -6.5; P < .02), and anxiety, fatigue, and cancer and treatment distress symptoms (beta(s) = 0.4, 0.6, and 0.3, respectively; P < .03). CONCLUSION: Patients with a malignancy who experience delirium during myeloablative HSCT showed impaired neurocognitive abilities and persistent distress 80 days after transplantation. Effective prevention or treatment of delirium during HSCT may improve both cognitive and psychological outcomes.

Clinical presentation of delirium in patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Delirium is common in patients undergoing hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and excess mortality in diverse patient samples. Although delirium can be treated successfully, it is largely undiagnosed. Understanding the clinical presentation of delirium may help improve the recognition of delirium in these patients. In the current study, the authors investigated the clinical presentation of delirium in HSCT patients, including the time course of these symptoms and comorbid affective distress, fatigue, and pain. METHODS: Ninety patients ages 22-62 years were recruited prior to undergoing their first allogeneic or autologous HSCT. Delirium, distress, and pain symptom assessments were conducted prospectively 3 times per week from pretransplantation through Day 30 posttransplantation. RESULTS: Delirium episodes occurred in 50% of patients and lasted approximately 10 days, with peak severity at the end of the second week posttransplantation. Factor analysis revealed three groups of delirium symptoms representing psychosis-behavior, cognition, and mood-consciousness. Delirium episodes were characterized by rapid onset of psychomotor and sleep-wake cycle disturbance that persisted and cognitive symptoms that continued to worsen throughout much of the episode. Rises in psychosis-behavior and cognitive symptoms predated the start of delirium episodes by approximately 4 days. Affective distress and fatigue were common and appeared to be associated most with psychosis-behavioral delirium symptoms. CONCLUSIONS: The results describe in detail the clinical presentation of delirium in patients undergoing HSCT. Affective distress and fatigue commonly were associated with delirium. These findings may aid clinicians in improving the recognition and treatment of delirium in this population and avoiding further morbidity and potential mortality.

Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant.

Research indicates that myeloablative hematopoietic cell transplantation (HCT) impairs neurocognitive function. However, prospective studies on long-term effects are lacking. This longitudinal study examined neurocognitive changes over the first year in 142 adult recipients of allogeneic HC transplants who received neuropsychologic testing before transplantation and again after 80 days and 1 year. Age-, sex-, and education-adjusted population-based standardized scores were used for normative comparisons. Performance on all tests declined from before transplantation to 80 days (P < .05) and improved by 1 year (P < .05), returning to pretransplantation levels on all tests except for grip strength and motor dexterity. Although verbal fluency and memory recovered by 1 year, both were below norms at all 3 testing times (P < .01). Logistic regressions indicated that patients without chemotherapy, other than hydroxyurea, previous to HCT and patients not receiving chronic graft-versus-host disease (GVHD) medication at 1 year had lower risk of impaired function (P < .05). In conclusion, HCT was associated with significant generalized decline in neurocognitive performance at 80 days, with subsequent recovery to pretransplantation levels by 1 year for most survivors, except on motor tasks. Results indicate that long-term cognitive decrements, as distinct from motor disabilities, infrequently derive directly from HCT.

Delirium in patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Delirium is common in patients with malignant disease and is associated with significant morbidity. Studies have not examined the epidemiology of delirium in patients undergoing hematopoietic stem cell transplantation (HSCT). The objectives of this study were to determine the prevalence, incidence, severity, and duration of delirium in the acute phase of HSCT and to determine the pretransplantation risk factors for the occurrence and severity of delirium during this period. METHODS: Ninety adult patients with malignancies who were admitted to the Fred Hutchinson Cancer Research Center for their first HSCT were assessed prospectively from 1 week pretransplantation to 30 days posttransplantation. Delirium occurrence using the Delirium Rating Scale (DRS) and severity using the Memorial Delirium Assessment Scale (MDAS) were assessed three times per week. Pretransplantation risk factors were assessed by patient self-report, charts, and computerized records. RESULTS: The cumulative posttransplantation incidence of delirium events (DRS score > 12) was 66 (73%), and the incidence of delirium episodes (DRS score > 12 for 2 of 3 consecutive assessments) was 45 (50%). The mean +/- standard deviation duration of delirium episodes was 4.8 +/- 2.8 assessments (approximately 10 days). Pretransplantation risk factors for having a delirium episode were lower cognitive functioning (Trailmaking B test [a standardized test of visual conceptual and visuomotor tracking and cognitive flexibility]; P = 0.0008), higher blood urea nitrogen (P = 0.002), higher alkaline phosphatase (P = 0.008), lower physical functioning (SF-12 [self report questionnaire that is a general measure of functioning]; P = 0.03), and higher magnesium (P = 0.03). Pretransplantation risk factors for higher delirium severity scores were higher creatinine (P < 0.0001), the presence of total body irradiation (P = 0.0001), higher magnesium (P = 0.0003), lower Mini-Mental State Examination score (P = 0.002), malignancy diagnosis category (P = 0.002), female gender (P = 0.008), higher alkaline phosphatase (P = 0.02), older age (P = 0.03), and prior alcohol or drug abuse (P = 0.046). CONCLUSIONS: Half of patients who undergo HSCT experience a delirium episode during the 4 weeks posttransplantation. Pretransplantation risk factors can assist in identifying patients who are more likely to develop delirium posttransplantation.