Cognitive impairment is well-recognized after myeloablative allogeneic hematopoietic cell transplantation (HCT). However, cognitive functioning after reduced-intensity allogeneic or autologous HCT remains unclear.

A total of 477 HCT recipients (236 autologous, 128 reduced-intensity allogeneic, 113 myeloablative allogeneic) underwent standardized neuropsychologic testing before HCT and at 6 months and 1, 2, and 3 years after HCT. Ninety-nine frequency-matched healthy controls underwent testing at commensurate time points. Primary outcomes of the study were practice effect–adjusted domain-specific T scores and global deficit scores. Piecewise generalized estimating equation models were used to compare groups and to identify associated variables and post-HCT trends of cognitive impairment.

Median age was 52 years (range, 18 to 74 years) for HCT recipients and 55 years (range, 19 to 73 years) for controls. Post-HCT scores were comparable between controls and autologous and reduced-intensity HCT recipients. Myeloablative HCT recipients had significantly lower (P < .001) post-HCT scores than controls for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity. Pre-HCT to 6 months post-HCT scores did not change after reduced-intensity HCT but declined significantly for fine motor dexterity (P < .001) after myeloablative HCT. However, pre-HCT to 3 years post-HCT scores declined significantly (P < .003) in reduced-intensity HCT recipients for executive function, verbal fluency, and working memory. Older age, male sex, and lower education, income, and cognitive reserve were associated with post-HCT cognitive impairment. At 3 years post-HCT, global cognitive impairment was present in 18.7% of autologous and 35.7% of allogeneic HCT recipients.

Myeloablative allogeneic HCT recipients showed significant cognitive decline compared with healthy controls. Reduced-intensity allogeneic HCT recipients showed evidence of delayed decline. Cognitive functioning in autologous HCT recipients generally was spared. The study identified vulnerable subpopulations that could benefit from targeted interventions.

Impaired cognition is an increasingly recognized consequence of myeloablative allogeneic hematopoietic cell transplantation (HCT)1,2 and could affect societal reintegration and return to work or school.3,4 Potentially neurotoxic agents, including cranial and total body irradiation, high-dose chemotherapy, intrathecal methotrexate, and corticosteroids, place cancer survivors at risk for cognitive impairment.5,6 Decline in memory, learning, attention/concentration, and psychomotor and executive functioning have been reported after HCT,1 with recovery for most domains by 5 years.2 Nonetheless, deficits remain for 40% of survivors.2

Previous studies in HCT patients have been limited by small sample sizes, cross-sectional study designs, lack of a healthy comparison group, and limited inclusion of autologous HCT recipients.2,7-15 These limitations likely have contributed to mixed evidence with respect to the extent and nature of cognitive compromise in HCT survivors.16 In addition, the increasing use of reduced-intensity conditioning demands an understanding of the trajectory of cognitive functioning in this growing population.17 We addressed these gaps by establishing a prospective cohort of adults who underwent autologous or allogeneic HCT for hematologic malignancies and a healthy comparison group. Our goal was to determine the longitudinal trajectory of cognitive functioning by using standardized neuropsychologic assessments from before HCT to 3 years after HCT and to identify host- and treatment-related factors associated with cognitive impairment and, thus, the identification of high-risk subpopulations for future targeted interventions.

Study Population and Design

Patients scheduled to receive autologous or allogeneic HCT for hematologic malignancies at City of Hope between 2005 and 2011 were approached for study participation. Participants were at least 18 years of age and English literate and provided informed consent. Eligible controls without a chronic health condition (frequency matched for age at enrollment, sex, and annual household income) were recruited from family and friends of study participants or from the community. HCT recipients and controls were excluded if they had a preexisting neurologic or major psychiatric disorder; significant auditory, visual, or motor impairments; or neuropsychologic interventions within 6 months of study participation. The study was approved by the institutional review board at City of Hope. Informed consent was provided according to the Declaration of Helsinki.

The study used a prospective, longitudinal design to assess cognitive functioning by using standardized neuropsychologic tests administered at five predetermined time points: pre-HCT (median of 16 days before HCT), 6 months (−45 to 95 days), 1 year (−1.4 to 4.1 months), 2 years (−3.3 to 4.9 months), and 3 years (−4.2 to 6.4 months) after HCT. Tests were administered to controls at commensurate time points. Fourteen standardized tests (Data Supplement) covered eight domains of cognitive functioning (executive function, verbal fluency, verbal speed, processing speed, working memory, auditory memory, visual memory, and fine motor dexterity). Cognitive reserve was assessed at enrollment by using an intelligence quotient (IQ) estimate. Fatigue was evaluated at each study time point. A description of all instruments is provided in the Data Supplement.

Self-reported demographic information was obtained at study enrollment and on return to work after HCT. Medical records were used to abstract information about primary diagnosis, stem-cell source (autologous, sibling, or unrelated donor), preparative regimen, risk of relapse at HCT (standard or high risk), and remission status. For allogeneic HCT recipients, information was collected about conditioning intensity (reduced intensity or myeloablative) and presence of chronic graft-versus-host disease (cGVHD) at each time point.

Statistical Analysis

Raw test scores were transformed to approach normality such that higher transformed scores indicated better performance. The Data Supplement lists the direction and transformation of each raw score. Practice effects18 were estimated within controls and applied to HCT recipients with the assumption of comparable practice effects between HCT recipients and controls given similar demographic characteristics and testing time points (Data Supplement). Practice effects were measured by using generalized estimating equation (GEE) regression models19 that adjusted for the number of previous tests, time interval between two consecutive tests, age, sex, marital status, and IQ and were estimated as the magnitude of difference between test scores at two consecutive time points. Adjusted scores corrected for practice effects were calculated as the difference between the transformed raw scores and the estimated cumulative practice effects for controls and HCT recipients. Corrected scores were transformed to standardized T scores (mean, 50; standard deviation, 10).

We used piecewise GEE models (by using an indicator variable for modeling pre-HCT scores and overall post-HCT scores) to compare controls with autologous HCT recipients and with reduced-intensity and myeloablative allogeneic HCT recipients. We also compared reduced-intensity with myeloablative allogeneic HCT recipients. Next, within autologous and allogeneic cohorts, we compared pre-HCT scores with early (at 6 months) and late (at 3 years) post-HCT scores. Finally, we examined sociodemographic and clinical variables associated with cognitive impairment. Models with T scores were built by using backward selection of variables significant at P < .1, including demographic (age, sex, ethnicity, marital status, education, income) and clinical (fatigue, IQ, risk of relapse, disease status, primary diagnosis, preparative regimens) variables. By using Bonferroni’s method for multiple testing, a significance threshold of P ≤ .003 (.05/14 tests) was used to account for comparisons across groups.

A summary score of cognitive functioning called the global deficit score20-22 (Data Supplement) was calculated for all participants. A score of ≥ 0.5 (at least mild cognitive impairment) was used to identify the presence of global cognitive deficit.20 We used a GEE to model the odds of global cognitive deficit at each time point, the post-HCT overall risk of impairment, and the post-HCT trends over time that compared autologous and myeloablative and reduced-intensity allogeneic HCT recipients with controls. Trend models included a group-time interaction to examine the direction and magnitude of the global deficit score slope after HCT. The proportion of HCT recipients who had not returned to work by 3 years and the odds of not returning to work in association with global cognitive deficit were estimated. Models with the global cognitive deficit outcome were adjusted for demographic and clinical variables where significant, and a P value significance threshold of 5% was used. All analyses were performed with SAS 9.4 statistical software (SAS Institute, Cary, NC).

Participant Characteristics

A total of 477 HCT recipients (236 autologous, 128 reduced-intensity, and 113 myeloablative allogeneic) and 99 controls were enrolled in the study. Figure 1 shows participants at all time points. Sample size and power calculations are provided in the Data Supplement. The Data Supplement lists participants who completed testing at all time points and compares them with those who missed at least one time point. The most common reasons for attrition among HCT recipients were death (27.5%) and receipt of a second HCT (7.3%). Among eligible HCT recipients, 429 completed pre-HCT testing (89.9%), with 341 (81.6%) at 6 months, 308 (81.5%) at 1 year, 247 (80.7%) at 2 years, and 227 (81.4%) at 3 years.

Table 1 lists the demographic characteristics of HCT recipients and controls at enrollment. Age, sex, ethnicity, and income did not differ between HCT recipients and controls. HCT recipients had lower education (less than college graduate, 49.3% v 37.4%; P = .03) and lower cognitive reserve (IQ at or below the median for HCT recipients, 51.5% v 35.3%; P = .004). Median age at study enrollment for HCT recipients was 52.2 years (range, 18 to 74 years), 61.4% were male and 67.5% were non-Hispanic white (NHW), and 49.2% of allogeneic HCT recipients developed cGVHD.


Table 1. Demographic and Clinical Characteristics of Study Participants

Group Comparisons
Pre-HCT scores.
HCT recipients versus controls.

No statistically significant differences were found between autologous HCT recipients and controls or between reduced-intensity allogeneic HCT recipients and controls. Myeloablative allogeneic HCT recipients had significantly lower pre-HCT scores (P < .001) than controls for processing speed (Table 2; Fig 2A).


Table 2. Pairwise Comparisons of Pre-HCT and Overall Post-HCT T Scores Between Autologous, Reduced-Intensity Allogeneic, and Myeloablative Allogeneic HCT Recipients and Healthy Controls

Myeloablative versus reduced-intensity allogeneic HCT recipients.

Pre-HCT scores were comparable across all domains.

Post-HCT scores.
HCT recipients versus controls.

No statistically significant differences were found in overall post-HCT scores between autologous HCT recipients and controls or between reduced-intensity allogeneic HCT recipients and controls. Myeloablative allogeneic HCT recipients had significantly lower scores (P ≤ .003) for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity (Table 2; Fig 2A).

Myeloablative versus reduced-intensity allogeneic HCT recipients.

Myeloablative allogeneic recipients had significantly lower overall post-HCT scores (P ≤ .003) than reduced-intensity recipients for verbal speed and processing speed.

Trajectory of cognitive functioning among HCT recipients.
Autologous HCT.

Compared with pre-HCT scores, autologous HCT recipients had significantly higher post-HCT scores (P ≤ .003) in verbal fluency at 6 months and 3 years. Significantly lower scores (P ≤ .003) were observed at 3 years for visual memory and at 6 months and 3 years for fine motor dexterity. Lower scores were observed at 6 months for verbal speed but reached pre-HCT scores at 3 years (Table 3).


Table 3. Comparison of Pre-HCT T Scores With Early and Late Post-HCT T Scores Among Autologous, Reduced-Intensity Allogeneic, and Myeloablative Allogeneic HCT Recipients

Reduced-intensity allogeneic HCT.

No differences were found between the pre-HCT and 6-month post-HCT scores. Significantly lower scores (P ≤ .003) were observed at 3 years for executive function, verbal fluency, and working memory.

Myeloablative allogeneic HCT.

Significantly lower scores (P ≤ .003) were observed at 6 months and 3 years for fine motor dexterity.

Variables associated with post-HCT cognitive impairment.
Autologous HCT.

Variables associated with significantly worse (P ≤ .003) post-HCT cognitive scores were older age at time of test (all domains except verbal fluency and auditory memory), male sex (all domains except verbal speed, working memory, auditory memory, and fine motor dexterity), female sex (working memory), ethnicity other than NHW (working memory), lower education (executive function, verbal fluency, processing speed, and working memory), low income (executive function, verbal speed, processing speed, and working memory); and low cognitive reserve (all domains except visual memory and fine motor dexterity; Table 4).


Table 4. Demographic and Clinical Variables Associated With Post-HCT T Scores for Autologous, Reduced-Intensity, and Myeloablative Allogeneic HCT Recipient

Reduced-intensity allogeneic HCT.

Variables associated with significantly worse (P ≤ .003) cognitive scores were older age at time of test (all domains except verbal fluency and auditory memory), male sex (all domains except auditory memory, visual memory, and fine motor dexterity), female sex (working memory), and lower cognitive reserve (all domains except verbal speed, visual memory, and fine motor dexterity).

Myeloablative allogeneic HCT.

Variables associated with significantly worse cognitive scores (P ≤ .003) were older age at time of test (executive function, processing speed, working memory, and visual memory), female sex (working memory), ethnicity other than NHW (verbal fluency), lower education (verbal fluency and working memory), lower income (processing speed and auditory memory), and lower cognitive reserve (all domains except auditory memory, visual memory, and fine motor dexterity).

Global cognitive deficit.
Autologous HCT.

No statistically significant differences were found in the prevalence of global cognitive deficit between autologous HCT recipients and controls before HCT (22.5% v 17.2%; P = .3) or 3 years after HCT (18.7% v 8.7%, P = .1; Data Supplement). Adjusted risk of global cognitive deficit was comparable with that of controls (odds ratio [OR], 1.35; 95% CI, 0.7 to 2.7; Fig 2B; Data Supplement). Older age (OR, 1.05; 95% CI, 1.02 to 1.08), male sex (OR, 5.3; 95% CI, 2.4 to 11.1), lower income (< $50,000: OR, 7.1 [95% CI, 2.7 to 18.6]; $50,000 to $100,000: OR, 3.5 [95% CI, 1.5 to 8.0]), and lower cognitive reserve (OR, 10.0; 95% CI, 4.5 to 25.0) were associated with global cognitive deficit after HCT (Data Supplement).

Reduced-intensity allogeneic HCT.

Prevalence of global cognitive deficit was comparable with controls before HCT and at 6 months and 1 and 2 years after HCT but was significantly higher at 3 years after HCT (35.4% v 8.7%; P = .001; Data Supplement). Although the adjusted risk for global cognitive deficit was not elevated at any of the post-HCT time points, the trend of impairment increased significantly over time (OR, 1.8; 95% CI, 1.3 to 2.5; Fig 2B; Data Supplement). Older age (OR, 1.11; 95% CI, 1.05 to 1.17) and low cognitive reserve (OR, 7.1; 95% CI, 2.9 to 16.7) were associated with global cognitive deficit after HCT (Data Supplement).

Myeloablative allogeneic HCT.

Prevalence of global cognitive deficit was comparable with that of controls before HCT (22.3% v 17.2%; P = .4), but was significantly higher at 6 months (31.1% v 16.5%; P = .03), 2 years (34.6% v 16.4%; P = .02), and 3 years after HCT (36% v 8.7%; P = .002; Data Supplement). Adjusted risk of global cognitive deficit was significantly higher than that of controls (OR, 3.5; 95% CI, 1.5 to 7.9) and increased over time (OR, 1.3; 95% CI, 1.0 to 1.8; Fig 2B, Data Supplement). Older age (OR, 1.06; 95% CI, 1.02 to 1.1) and ethnicity other than NHW (OR, 5.6; 95% CI, 1.8 to 17.7) were associated with global cognitive deficit after HCT among myeloablative allogeneic HCT recipients (Data Supplement).

Return to work.

Overall, 29.5% of HCT recipients who participated at the 3-year time point had not returned to work (autologous, 19.5%; reduced-intensity allogeneic, 31.2%; myeloablative allogeneic HCT, 46.3%). Multivariable analysis (Data Supplement) showed no association between global cognitive deficit and not returning to work by 3 years after HCT in autologous HCT recipients (OR, 0.4; 95% CI, 0.04 to 3.3). However, in allogeneic HCT recipients, global cognitive deficit was associated with a 9.9-fold increased odds of not returning to work (95% CI, 2.4 to 40.2).

In this longitudinal assessment of cognitive functioning in adult HCT recipients, we found that post-HCT cognitive functioning in autologous and reduced-intensity allogeneic HCT recipients was comparable with that of healthy controls. However, myeloablative allogeneic HCT recipients had worse cognitive functioning after HCT in five of the eight domains examined. Compared with pre-HCT performance, autologous HCT recipients showed improvement in verbal fluency but a decline in visual memory and fine motor dexterity. Myeloablative allogeneic HCT recipients showed early decline in fine motor dexterity that persisted up to 3 years. Although no decline was observed at 6 months for reduced-intensity allogeneic HCT recipients, evidence showed a delayed decline in executive function, verbal fluency, and working memory at 3 years after HCT.

Previous studies that focused on autologous HCT showed improvement in cognitive functioning over time,23-26 whereas those that focused on allogeneic HCT recipients showed a decline after HCT with limited recovery over time.7,8,14 Most studies, however, focused primarily on myeloablative HCT recipients.8,11,27,28 In the current cohort, > 50% of the allogeneic HCT recipients received reduced-intensity conditioning, which allowed us to make the novel observation that the post-HCT cognitive trajectory for reduced-intensity allogeneic recipients resembles that of healthy controls, albeit with a delayed decline. On the other hand, global cognitive deficit was apparent at 6 months after HCT in myeloablative allogeneic HCT recipients, with no improvement at 3 years. The goal of reduced-intensity allogeneic HCT is to reduce early regimen-related toxicity17,29; this likely explains the low risk of cognitive impairment in the early post-transplantation period (6 months). The delayed cognitive decline in this group possibly is analogous to the risk of radiation-related adverse events, such as cataracts, where patients who receive single-dose total body irradiation have a shorter latency and a higher risk of cataracts; on the other hand, those who receive fractionated total body irradiation develop cataracts much later after exposure, and the risk is not as high.30

We identified older age, male sex, lower education and income, and lower cognitive reserve as predictors of post-HCT cognitive impairment across all HCT types. Similar to a previous study,8 we did not find an association between cognitive functioning and specific therapeutic exposures used in preparative regimens or with cGVHD. Older age, lower education, higher fatigue, and lower cognitive reserve have previously been described as predictors of cognitive decline after allogeneic HCT,8,10 and early recovery of cognitive functioning was reported among patients with greater cognitive reserve.31

In the current cohort, females had higher performance across all tests except for working memory tests that measure attention and arithmetic abilities. The lower cognitive performance in males in this study contrasts with a higher risk of cognitive impairment in female childhood cancer survivors32 and greater self-reported cognitive symptoms among adult female HCT survivors.33 In the general population, females have an advantage in verbal skills, processing speed, executive function, and the fine motor domain, whereas males outperform females in visuospatial, working memory, and mathematical abilities.34-36 Sex differences in cognitive functioning are likely influenced by the effects of estrogen (and testosterone through its conversion into estrogen) on the CNS.36-39 Although hypogonadism is observed frequently after HCT in both males and females, females are more likely to be supplemented with hormone replacement. Persistent untreated hypogonadism could possibly explain the lower performance observed in male HCT survivors; however, we were unable to evaluate this in the current study.

Findings from this large, prospectively followed cohort need to be placed in the context of the study’s limitations. The study was conducted at a single institution and could be limited by clinical practices unique to the institution. However, transplantation practices usually follow standard operating procedures mandated by cellular therapy–accrediting organizations; these regulatory processes minimize heterogeneity in clinical practice across transplantation centers. Neuropsychologic tests in the United States generally are normed and standardized in English-speaking individuals; validated instruments for use in non–English-speaking populations were not available when we conducted the study. Furthermore, these tests were originally developed to identify impairments associated with moderate to severe brain damage and, therefore, may not be sensitive in detecting mild dysfunction typically associated with cancer-related toxicities. Unavoidable attrition over the course of the study as a result of post-HCT illness or death could have introduced bias in the magnitude of cognitive impairment; however, among those alive and able to participate, the average participation rate was 83% across all time points. Although we found a 10-fold higher odds of not returning to work among allogeneic HCT recipients with global cognitive deficit at the 3-year time point, measures of anxiety, depression, financial toxicity, and quality of life were not collected longitudinally. Future directions of this research would involve comprehensive collection of functional and social outcomes data.

These limitations notwithstanding, this study had several strengths. We used a validated neuropsychological battery for objective assessment of cognitive functioning suitable for repeated administration in a longitudinal study that adjusted for practice effects. This adjustment is especially relevant for the evaluation of cognitive change across multiple time points and global performance scores over time.40,41 We used a novel approach to estimate practice effects while taking advantage of the data collected on healthy controls. We believe that our approach improved the accuracy of the estimation of practice effect in the study population by measuring practice effects in a population comparable to patients with respect to demographics and testing time points. Direct comparison with healthy controls also facilitated the contrast of cognitive changes in HCT recipients over time. The sufficiently large sample size allowed for valid comparisons by HCT type and conditioning intensity.1 Predetermined time points for assessment, including the pre-HCT assessment, provided a means to observe patterns and determinants of change in cognitive functioning during both the short-term and the long-term post-HCT period.

In conclusion, at 3 years after HCT, 18% of autologous HCT recipients and 35.7% of allogeneic HCT recipients demonstrated global cognitive deficits. Compared with healthy controls, myeloablative allogeneic HCT recipients were the most compromised, with evidence of cognitive impairment in multiple domains. Reduced-intensity allogeneic and autologous HCT recipients demonstrated cognitive functioning comparable to controls, with evidence for delayed cognitive impairment in reduced-intensity allogeneic HCT recipients. Allogeneic HCT recipients with global cognitive deficits were at a 10-fold increased risk of not returning to work, which suggests that cognitive impairment is a significant barrier to societal reintegration for this vulnerable population. Cognitive functioning needs to be monitored after HCT among patients identified to be at the highest risk to facilitate targeted cognitive interventions such as cognitive training.42-48

© 2017 by American Society of Clinical Oncology

Supported in part by the Leukemia and Lymphoma Society (62771-11 to S.B.).

Presented at the American Society of Hematology 55th Annual Meeting, New Orleans, LA, December 7-10, 2013.

Conception and design: Sunita K. Patel, Stephen J. Forman, Smita Bhatia

Financial support: Smita Bhatia

Administrative support: Smita Bhatia

Provision of study materials or patients: Smita Bhatia

Collection and assembly of data: Alysia Bosworth, Emily Morse, Molly Mather, Liton Francisco, Smita Bhatia

Data analysis and interpretation: Noha Sharafeldin, Yanjun Chen, Canlan Sun, F. Lennie Wong, Smita Bhatia

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

Cognitive Functioning After Hematopoietic Cell Transplantation for Hematologic Malignancy: Results From a Prospective Longitudinal Study

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to or

Noha Sharafeldin

No relationship to disclose

Alysia Bosworth

No relationship to disclose

Sunita K. Patel

No relationship to disclose

Yanjun Chen

No relationship to disclose

Emily Morse

No relationship to disclose

Molly Mather

No relationship to disclose

Canlan Sun

No relationship to disclose

Liton Francisco

No relationship to disclose

Stephen J. Forman

Patents, Royalties, Other Intellectual Property: Mustang Bio

F. Lennie Wong

No relationship to disclose

Smita Bhatia

No relationship to disclose

1. Syrjala KL, Dikmen S, Langer SL, et al: Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant. Blood 104:3386-3392, 2004 Crossref, MedlineGoogle Scholar
2. Syrjala KL, Artherholt SB, Kurland BF, et al: Prospective neurocognitive function over 5 years after allogeneic hematopoietic cell transplantation for cancer survivors compared with matched controls at 5 years. J Clin Oncol 29:2397-2404, 2011 LinkGoogle Scholar
3. Zakzanis KK, Grimes KM: Relationship among apathy, cognition, and real-world disability after mild traumatic brain injury. Appl Neuropsychol Adult 24:559-565, 2017 Crossref, MedlineGoogle Scholar
4. Kirchhoff AC, Leisenring W, Syrjala KL: Prospective predictors of return to work in the 5 years after hematopoietic cell transplantation. J Cancer Surviv 4:33-44, 2010 Crossref, MedlineGoogle Scholar
5. Wefel JS, Kesler SR, Noll KR, et al: Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA Cancer J Clin 65:123-138, 2015 Crossref, MedlineGoogle Scholar
6. Ganz PA, Kwan L, Castellon SA, et al: Cognitive complaints after breast cancer treatments: Examining the relationship with neuropsychological test performance. J Natl Cancer Inst 105:791-801, 2013 Crossref, MedlineGoogle Scholar
7. Jim HS, Small B, Hartman S, et al: Clinical predictors of cognitive function in adults treated with hematopoietic cell transplantation. Cancer 118:3407-3416, 2012 Crossref, MedlineGoogle Scholar
8. Scherwath A, Schirmer L, Kruse M, et al: Cognitive functioning in allogeneic hematopoietic stem cell transplantation recipients and its medical correlates: A prospective multicenter study. Psychooncology 22:1509-1516, 2013 Crossref, MedlineGoogle Scholar
9. Meyers CA, Weitzner M, Byrne K, et al: Evaluation of the neurobehavioral functioning of patients before, during, and after bone marrow transplantation. J Clin Oncol 12:820-826, 1994 LinkGoogle Scholar
10. Harder H, Cornelissen JJ, Van Gool AR, et al: Cognitive functioning and quality of life in long-term adult survivors of bone marrow transplantation. Cancer 95:183-192, 2002 Crossref, MedlineGoogle Scholar
11. Booth-Jones M, Jacobsen PB, Ransom S, et al: Characteristics and correlates of cognitive functioning following bone marrow transplantation. Bone Marrow Transplant 36:695-702, 2005 Crossref, MedlineGoogle Scholar
12. Wefel JS, Vardy J, Ahles T, et al: International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol 12:703-708, 2011 Crossref, MedlineGoogle Scholar
13. Sostak P, Padovan CS, Yousry TA, et al: Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology 60:842-848, 2003 Crossref, MedlineGoogle Scholar
14. Schulz-Kindermann F, Mehnert A, Scherwath A, et al: Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies. Bone Marrow Transplant 39:789-799, 2007 Crossref, MedlineGoogle Scholar
15. Tannock IF, Ahles TA, Ganz PA, et al: Cognitive impairment associated with chemotherapy for cancer: Report of a workshop. J Clin Oncol 22:2233-2239, 2004 LinkGoogle Scholar
16. Phillips KM, McGinty HL, Cessna J, et al: A systematic review and meta-analysis of changes in cognitive functioning in adults undergoing hematopoietic cell transplantation. Bone Marrow Transplant 48:1350-1357, 2013 Crossref, MedlineGoogle Scholar
17. Petersen SL: Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. Dan Med Bull 54:112-139, 2007 MedlineGoogle Scholar
18. Goldberg TE, Harvey PD, Wesnes KA, et al: Practice effects due to serial cognitive assessment: Implications for preclinical Alzheimer’s disease randomized controlled trials. Alzheimers Dement (Amst) 1:103-111, 2015 Crossref, MedlineGoogle Scholar
19. Hubbard AE, Ahern J, Fleischer NL, et al: To GEE or not to GEE: Comparing population average and mixed models for estimating the associations between neighborhood risk factors and health. Epidemiology 21:467-474, 2010 Crossref, MedlineGoogle Scholar
20. Carey CL, Woods SP, Gonzalez R, et al: Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol 26:307-319, 2004 Crossref, MedlineGoogle Scholar
21. Blackstone K, Moore DJ, Franklin DR, et al: Defining neurocognitive impairment in HIV: Deficit scores versus clinical ratings. Clin Neuropsychol 26:894-908, 2012 Crossref, MedlineGoogle Scholar
22. Vardy J, Rourke S, Tannock IF: Evaluation of cognitive function associated with chemotherapy: A review of published studies and recommendations for future research. J Clin Oncol 25:2455-2463, 2007 LinkGoogle Scholar
23. Ahles TA, Tope DM, Furstenberg C, et al: Psychologic and neuropsychologic impact of autologous bone marrow transplantation. J Clin Oncol 14:1457-1462, 1996 LinkGoogle Scholar
24. Chang G, Meadows ME, Orav EJ, et al: Mental status changes after hematopoietic stem cell transplantation. Cancer 115:4625-4635, 2009 Crossref, MedlineGoogle Scholar
25. Wenz F, Steinvorth S, Lohr F, et al: Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI). Int J Radiat Oncol Biol Phys 48:1497-1501, 2000 Crossref, MedlineGoogle Scholar
26. Jacobs SR, Small BJ, Booth-Jones M, et al: Changes in cognitive functioning in the year after hematopoietic stem cell transplantation. Cancer 110:1560-1567, 2007 Crossref, MedlineGoogle Scholar
27. Harder H, Van Gool AR, Cornelissen JJ, et al: Assessment of pre-treatment cognitive performance in adult bone marrow or haematopoietic stem cell transplantation patients: A comparative study. Eur J Cancer 41:1007-1016, 2005 Crossref, MedlineGoogle Scholar
28. Harder H, Van Gool AR, Duivenvoorden HJ, et al: Case-referent comparison of cognitive functions in patients receiving haematopoietic stem-cell transplantation for haematological malignancies: Two-year follow-up results. Eur J Cancer 43:2052-2059, 2007 Crossref, MedlineGoogle Scholar
29. Bearman SI: Reduced-intensity allogeneic stem cell transplantation. Curr Hematol Rep 2:277-286, 2003 MedlineGoogle Scholar
30. Fahnehjelm KT, Törnquist AL, Olsson M, et al: Visual outcome and cataract development after allogeneic stem-cell transplantation in children. Acta Ophthalmol Scand 85:724-733, 2007 Crossref, MedlineGoogle Scholar
31. Beglinger LJ, Duff K, Van Der Heiden S, et al: Neuropsychological and psychiatric functioning pre- and posthematopoietic stem cell transplantation in adult cancer patients: A preliminary study. J Int Neuropsychol Soc 13:172-177, 2007 Crossref, MedlineGoogle Scholar
32. Armstrong GT, Sklar CA, Hudson MM, et al: Long-term health status among survivors of childhood cancer: Does sex matter? J Clin Oncol 25:4477-4489, 2007 LinkGoogle Scholar
33. Sanders JE, Hoffmeister PA, Storer BE, et al: The quality of life of adult survivors of childhood hematopoietic cell transplant. Bone Marrow Transplant 45:746-754, 2010 Crossref, MedlineGoogle Scholar
34. Sherwin BB: Estrogen and cognitive functioning in women: Lessons we have learned. Behav Neurosci 126:123-127, 2012 Crossref, MedlineGoogle Scholar
35. Zaidi ZF: Gender differences in human brain: A review. Open Anat J 2:37-55, 2010 CrossrefGoogle Scholar
36. Upadhayay N, Guragain S: Comparison of cognitive functions between male and female medical students: A pilot study. J Clin Diagn Res 8:BC12-BC15, 2014 MedlineGoogle Scholar
37. Wallentin M: Putative sex differences in verbal abilities and language cortex: A critical review. Brain Lang 108:175-183, 2009 Crossref, MedlineGoogle Scholar
38. Chung WC, Auger AP: Gender differences in neurodevelopment and epigenetics. Pflugers Arch 465:573-584, 2013 Crossref, MedlineGoogle Scholar
39. Upadhayay N, Paudel BH, Singh PN, et al: Pre- and postovulatory auditory brainstem response in normal women. Indian J Otolaryngol Head Neck Surg 66:133-137, 2014 (suppl 1) Crossref, MedlineGoogle Scholar
40. McCaffrey RJ, Duff K, Westervelt HJ (eds): Practitioner’s Guide to Evaluating Change With Neuropsychological Assessment Instruments. New York, NY: Kluwer Academic, 2000 Google Scholar
41. Duff K, Beglinger LJ, Schultz SK, et al: Practice effects in the prediction of long-term cognitive outcome in three patient samples: A novel prognostic index. Arch Clin Neuropsychol 22:15-24, 2007 Crossref, MedlineGoogle Scholar
42. Von Ah D, Jansen CE, Allen DH: Evidence-based interventions for cancer- and treatment-related cognitive impairment. Clin J Oncol Nurs 1817-25, 2014 (suppl 18) Crossref, MedlineGoogle Scholar
43. Kesler S, Hadi Hosseini SM, Heckler C, et al: Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors. Clin Breast Cancer 13:299-306, 2013 Crossref, MedlineGoogle Scholar
44. Damholdt MF, Mehlsen M, O’Toole MS, et al: Web-based cognitive training for breast cancer survivors with cognitive complaints—A randomized controlled trial. Psychooncology 25:1293-1300, 2016 Crossref, MedlineGoogle Scholar
45. Hassler MR, Elandt K, Preusser M, et al: Neurocognitive training in patients with high-grade glioma: A pilot study. J Neurooncol 97:109-115, 2010 Crossref, MedlineGoogle Scholar
46. Poppelreuter M, Weis J, Bartsch HH: Effects of specific neuropsychological training programs for breast cancer patients after adjuvant chemotherapy. J Psychosoc Oncol 27:274-296, 2009 Crossref, MedlineGoogle Scholar
47. Sitzer DI, Twamley EW, Jeste DV: Cognitive training in Alzheimer’s disease: A meta-analysis of the literature. Acta Psychiatr Scand 114:75-90, 2006 Crossref, MedlineGoogle Scholar
48. Kane RL, Butler M, Fink HA, et al: Interventions To Prevent Age-Related Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer’s-Type Dementia. Rockville, MD, Agency for Healthcare Research and Quality, 2017 Google Scholar


No companion articles


DOI: 10.1200/JCO.2017.74.2270 Journal of Clinical Oncology 36, no. 5 (February 10, 2018) 463-475.

Published online December 18, 2017.

PMID: 29252122

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