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1.  Body Composition After Bone Marrow Transplantation in Childhood 
Oncology nursing forum  2012;39(2):186-192.
Purpose/Objectives
To describe the body composition and fat distribution of childhood bone marrow transplantation (BMT) survivors at least one year post-transplantation and examine the ability of the Centers for Disease Control and Prevention criteria to identify survivors with elevated body fat percentage.
Design
Cross-sectional, descriptive.
Setting
Pediatric oncology program at a National Cancer Institute–designated comprehensive cancer center.
Sample
48 childhood BMT survivors (27 males and 21 females).
Methods
Measurements included dual-energy x-ray absorptiometry scan, height, weight, and physical activity. Descriptive statistics were reported and mixed-model linear regression models were used to describe findings and associations.
Main Research Variables
Total body fat percentage and central obesity (defined as a ratio of central to peripheral fat of 1 or greater).
Findings
Fifty-four percent of survivors had body fat percentages that exceeded recommendations for healthy body composition and 31% qualified as having central obesity. Previous treatment with total body irradiation was associated with higher body fat percentage and central obesity, and graft-versus-host disease was associated with lower body fat percentage. The body mass index (BMI) criteria did not correctly identify the BMT survivors who had elevated body fat percentage.
Conclusions
Survivors of childhood BMT are at risk for obesity and central obesity that is not readily identified with standard BMI criteria.
Implications for Nursing
Nurses caring for BMT survivors should include evaluation of general and central obesity in their assessments. Patient education materials and resources for healthy weight and muscle building should be made available to survivors. Research is needed to develop appropriate interventions.
doi:10.1188/12.ONF.186-192
PMCID: PMC4251428  PMID: 22374492
2.  Allogeneic Bone Marrow Transplantation in First Remission for Children With Ultra-High-Risk Features of Acute Lymphoblastic Leukemia: A Children’s Oncology Group Study Report 
The prognosis for childhood acute lymphoblastic leukemia (ALL) has improved dramatically over the past quarter of a century. Despite improvements in the treatment of childhood ALL, relapse still occurs in 20 to 30% of patients. While many of these relapses occur in the “standard-risk” patients, approximately 10% of these patients present at diagnosis with clinical and biological features that identify them as very high risk of relapse. Children (2 months-21 years) with at least one ultra-high-risk feature (UHRF) of ALL in first remission treated on a frontline Children’s Cancer Group (CCG) ALL study with a matched family allogeneic donor were eligible for study entry onto CCG-1921 and an allogeneic bone marrow transplant (AlloBMT). Each patient received fractionated total body irradiation (1200 cGy) and cyclophosphamide (120 mg/kg) conditioning therapy followed by unmobilized bone marrow from a matched family donor. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and cyclosporin. Twenty-nine patients with median age of 8.7 years with UHRF ALL in first complete remission (CR1) received an AlloBMT from a family member. The incidence of grade II–IV acute GVHD was 20.7% and the incidence of chronic GVHD was 3.7%. AlloBMT conditioning regimen was well tolerated and only one patient (3%) had treatment-related mortality. Ten patients (35%) died due to progressive disease. The 5-year event free survival (EFS) for all patients was 58.6% and patients without cytogenetic abnormalities had a 5-year EFS of 77.8%. The 5-year EFS for infants and non-infants was 20.0% and 66.7% (log Rank p=0.01), respectively. Patients with Philadelphia chromosome positive ALL had a 5-year EFS of 66.7%. The children with UHRF of ALL may benefit from AlloBMT in CR1, especially patients with primary induction failure and Philadelphia chromosome positive ALL. Randomized prospective cooperative group studies are required to establish the role of allogeneic hematopoietic stem cell transplantation vs intensive chemotherapy in children with UHRF ALL in CR1.
doi:10.1016/j.bbmt.2006.09.013
PMCID: PMC2731715  PMID: 17241927
childhood acute lympoblastic leukemia; stem cell transplant; Philadelphia chromosome positive ALL; infantile ALL; induction failure
3.  Outcomes of Related Donor HLA-Identical or HLA-Haploidentical Allogeneic Blood or Marrow Transplantation for Peripheral T Cell Lymphoma 
The role of allogeneic blood or marrow transplantation (alloBMT) for peripheral T cell lymphoma (PTCL) remains to be defined. There is growing interest in reduced-intensity conditioning (RIC) regimens and/or utilization of human leukocyte antigen haploidentical (haplo) grafts given concerns about treatment-associated toxicities and donor availability. We reviewed the outcomes of 44 consecutive, related donor alloBMTs for PTCL performed at Johns Hopkins Hospital from 1994 to 2011, including 18 RIC/haplo alloBMTs. Patients receiving RIC (n = 24) were older, with median age of 59 years (range, 24 to 70), than patients receiving myeloablative conditioning (MAC, n = 20), with median age of 46 years (range, 18 to 64), P =.01. The median age at RIC/haplo alloBMT was 60 years. The estimated 2-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 26% to 55%) and overall survival (OS) was 43% (95% CI, 28% to 59%). In older patients (≥60, n = 14), the estimated 2-year PFS and OS were 38% (95% CI, 18% to 79%) and 45% (95% CI, 24% to 86%), respectively. On unadjusted analysis, there was a tendency toward superior outcomes for alloBMT in first remission versus beyond first remission, with an estimated 2-year PFS of 53% (95% CI, 33% to 77%) versus 29% (95% CI, 9% to 45%), P = .08. On competing risk analysis, the 1-year cumulative incidence of relapse was 38% for MAC/HLA-identical alloBMTs and 34% for RIC/haplo alloBMTs. Estimated 1-year nonrelapse mortality was 10% for MAC and 8% for RIC (11% for RIC/haplo alloBMT). On unadjusted landmark analysis, patients with acute grade II-IV or chronic graft-versus-host disease (GVHD) had a 17% probability of relapse (95% CI, 0% to 39%), compared with 66% (95% CI, 48% to 84%) in patients without GVHD, P = .04. Utilization of RIC and alternative donors expands treatment options in PTCL to those who are older and unable to tolerate high-dose conditioning, with outcomes comparable with approaches using myeloablative regimens and HLA-matched donors. AlloBMT may be appropriate in first remission in select high-risk cases.
doi:10.1016/j.bbmt.2013.01.006
PMCID: PMC4020434  PMID: 23370119
Peripheral T-cell lymphoma; Allogeneic blood or marrow; transplantation; Haploidentical; Reduced-intensity conditioning; Survival outcomes
4.  Impact of Disease Risk on Efficacy of Matched Related Bone Marrow Transplantation for Pediatric Acute Myeloid Leukemia: The Children's Oncology Group 
Journal of Clinical Oncology  2008;26(35):5797-5801.
Purpose
There is considerable variation in the use of HLA-matched related bone marrow transplantation (BMT) for the treatment of pediatric patients with newly diagnosed acute myeloid leukemia (AML). Some oncologists have argued that BMT should be offered to most patients in first complete remission (CR). Others have maintained that transplantation in first remission should be reserved for patients with high-risk disease. We performed this study to determine how disease risk influences the efficacy of BMT.
Methods
We combined data from four cooperative group clinical trials: Pediatric Oncology Group 8821, Children's Cancer Group (CCG) 2891, CCG 2961, and Medical Research Council 10. Using cytogenetics and the percentage of marrow blasts after the first course of chemotherapy, patients were stratified into favorable, intermediate, and poor-risk disease groups. Patients who could not be risk classified were analyzed separately. Outcomes for patients assigned to BMT and for patients assigned to chemotherapy alone were compared.
Results
The data set included 1,373 pediatric patients with AML in first CR. In the intermediate-risk group, the estimated disease-free survival at 8 years for patients who did not undergo transplantation was 39% ± 5% (2 SE), whereas it was 58% ± 7% for BMT patients. The estimated overall survival for patients who did not undergo transplantation was 51% ± 5%, whereas it was 62% ± 7% for BMT patients. Both differences were significant (P < .01). There were no significant differences for survival in the other two risk groups or in the non–risk-stratified patients.
Conclusion
Our study indicates that HLA-matched related BMT is an effective treatment for pediatric patients with intermediate-risk AML in first CR.
doi:10.1200/JCO.2007.13.5244
PMCID: PMC2645105  PMID: 18955460
5.  Prevalence and Predictors of Risky and Heavy Alcohol Consumption Among Adult Siblings of Childhood Cancer Survivors 
Psycho-oncology  2012;22(5):1134-1143.
Objective
To describe alcohol consumption patterns and risk factors for heavy alcohol use among siblings of childhood cancer survivors compared to survivors and national controls.
Methods
Secondary analysis of prospectively collected data from two national surveys was performed including a cohort of 3,034 adult siblings of childhood cancer survivors (age 18-56 years) and 10,398 adult childhood cancer survivors both from the Childhood Cancer Survivor Study, plus 5,712 adult participants from the population-based National Alcohol Survey. Cancer-related experiences, self-reported current health and mental health were examined in relation to alcohol consumption patterns including heavy and risky drinking.
Results
Adult siblings of childhood cancer survivors were more likely to be heavy drinkers (ORadj=1.3; 1.0-1.6) and risky drinkers (ORadj=1.3; 1.1-1.6) compared to controls from a national sample. Siblings were also more likely to drink at these two levels compared to survivors. Factors associated with heavy drinking among siblings include being 18-21 years old (ORadj=2.9; 2.0-4.4), male (ORadj=2.3; 1.7-3.0), having a high school education or less (ORadj=2.4; 1.7-3.5), and drinking initiation at a young age (ORadj=5.1; 2.5-10.3). Symptoms of depression, (ORadj=2.1; 1.3-3.2), anxiety (ORadj=1.9; 1.1-3.3) and global psychiatric distress (ORadj=2.5; 1.5-4.3) were significantly associated with heavy alcohol use.
Conclusions
Siblings of children with cancer are more likely to be heavy drinkers as adults compared to childhood cancer survivors or national controls. Early initiation of drinking and symptoms of psychological distress should be identified during early adolescence and effective sibling-specific interventions should be developed and made available for siblings of children with cancer.
doi:10.1002/pon.3121
PMCID: PMC3648621  PMID: 22736595
alcohol; childhood cancer; heavy drinking; risky drinking; siblings; cancer; alcohol/drug use; mental health; psychological impact
6.  Incidental Detection of Late Subsequent Intracranial Neoplasms with Magnetic Resonance Imaging Among Adult Survivors of Childhood Cancer 
Purpose
Survivors of childhood cancer are at increased risk of developing subsequent neoplasms. In long term survivors of childhood malignancies treated with and without cranial radiation therapy (CRT), undergoing unenhanced magnetic resonance imaging (MRI) of the brain, we estimated detection of intracranial neoplasms.
Methods
To investigate neurocognitive outcomes, 219 survivors of childhood cancer underwent unenhanced screening MRI of the brain. 164 of the survivors had been treated for acute lymphoblastic leukemia (ALL) (125 received CRT), and 55 for Hodgkin lymphoma (HL) (none received CRT). MRI examinations were reviewed and systematically coded by a single neuroradiologist. Demographic and treatment characteristics were compared for survivors with and without subsequent neoplasms.
Results
Nineteen of the 219 survivors (8.7%) had a total of 31 subsequent intracranial neoplasms identified by neuroimaging at a median time of 25 years (range 12-46 years) from diagnosis. All neoplasms occurred after CRT, except for a single vestibular schwannoma within the cervical radiation field in a HL survivor. The prevalence of subsequent neoplasms after CRT exposure was 14.4% (18 of 125). By noncontrast MRI, intracranial neoplasms were most suggestive of meningiomas. Most patients presented with no specific, localizing neurological complaints. In addition to the schwannoma, six tumors were resected based on results of MRI screening, all of which were meningiomas on histologic review.
Conclusion
Unenhanced brain MRI of long-term survivors of childhood cancer detected a substantial number of intracranial neoplasms. Screening for early detection of intracranial neoplasms among aging survivors of childhood cancer who received CRT should be evaluated.
Implications for Cancer Survivors
The high prevalence of incidentally detected subsequent intracranial neoplasms after CRT in long-term survivors of childhood cancer and the minimal symptoms reported by those with intracranial tumors in our study indicate that brain MRI screening of long-term survivors who received CRT may be warranted. Prospective studies of such screening are needed.
doi:10.1007/s11764-014-0344-8
PMCID: PMC4119575  PMID: 24488818
Survivors of Childhood Cancer; Cranial Radiation Therapy; Subsequent Intracranial Neoplasms; Meningiomas
7.  Longitudinal patterns of psychological distress in adult survivors of childhood cancer 
British Journal of Cancer  2013;109(5):1373-1381.
Background:
This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer.
Methods:
Participants included 4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported.
Results:
Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9% anxiety: 4.8% somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2% anxiety: 11.8% somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4–4.5; anxiety: OR=3.0; 95% CI=2.2–4.0; somatisation: OR=5.3; 95% CI=3.9–7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use.
Conclusion:
Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities.
doi:10.1038/bjc.2013.428
PMCID: PMC3778287  PMID: 23880828
psychological distress; survivorship; childhood cancer
8.  Prevalence of osteonecrosis and associated risk factors in children before allogenic bone marrow transplantation 
Bone marrow transplantation  2010;46(6):813-819.
Osteonecrosis (ON) is a debilitating long-term complication of allogenic bone marrow transplantation (alloBMT) but may begin before alloBMT in some children because of their primary disease treatment. Therefore, to estimate the prevalence and associated risk factors for ON before alloBMT, we conducted a retrospective analysis of magnetic resonance (MR) studies of 118 children who underwent first alloBMT at our institution between December 2000 and September 2007. Of the 118 consecutive patients, 107 (90.7%) underwent prospective MR studies irrespective of symptoms (69 males; median age at alloBMT 12.9 years), and 11 underwent MR studies for symptoms. Amongst the 107 who had prospective imaging, 23 (21.5%) had ON; nearly 50% had at least 30% epiphyseal involvement. Knees were more frequently involved than were hips; severity of ON was greater in hips. ON prevalence before alloBMT was 23.72% when all 118 patients were included in the denominator. Risk factor analysis, limited to MR studies performed irrespective of symptoms, revealed female gender (P = 0.049) and age ≥10 years at the time of MR study (P = 0.03) as significant risk factors and primary diagnosis of lymphoid malignancies and aplastic anemia trended towards significance. ON prior to alloBMT is a common occurrence in children.
doi:10.1038/bmt.2010.210
PMCID: PMC3010322  PMID: 20818446
Osteonecrosis; allogenic bone marrow transplantation; children; females; lymphoid malignancies; aplastic anemia
9.  Psychological Outcomes of Siblings of Cancer Survivors: A Report from the Childhood Cancer Survivor Study 
Psycho-oncology  2010;20(12):1259-1268.
Objective
To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer.
Methods
Cross-sectional, self-report data from 3,083 adult siblings (mean age 29 years, range 18-56 years) of 5+ year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression.
Results
Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98).
Conclusions
These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment.
doi:10.1002/pon.1848
PMCID: PMC3223600  PMID: 22114043
10.  The incidence of leukemia, lymphoma, and multiple myeloma among atomic bomb survivors: 1950 – 2001 
Radiation research  2013;179(3):10.1667/RR2892.1.
A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This paper presents analyses of radiation effects on leukemia, lymphoma, and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry-based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma, and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose response relationship and, to the extent the data allowed, to investigate variation in the excess risks with sex, attained age, exposure age, and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a non-linear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this non-linearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence that the radiation-associated excess leukemia risks, especially for acute myeloid leukemia, had persisted throughout the follow-up period out to – 55 years after the bombings. As in earlier analyses, there was a weak suggestion of a radiation dose response for non-Hodgkin lymphoma among men with no indication of such an effect among women. There was no evidence of radiation-associated excess risks for either Hodgkin lymphoma or multiple myeloma.
doi:10.1667/RR2892.1
PMCID: PMC3875218  PMID: 23398354
11.  Health-Related Quality of Life in Long-Term Survivors of Relapsed Childhood Acute Lymphoblastic Leukemia 
PLoS ONE  2012;7(5):e38015.
Background
Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL). Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL) was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors.
Methodology/Principal Findings
As part of the Swiss Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976–2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36), which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%). Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6) compared to those without (55.8;p=0.005), but after adjusting for self-reported late effects, this difference disappeared.
Conclusion/Significance
Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients’ HRQOL.
doi:10.1371/journal.pone.0038015
PMCID: PMC3360640  PMID: 22662262
12.  Reduced Cardiorespiratory Fitness in Adult Survivors of Childhood Acute Lymphoblastic Leukemia 
Pediatric blood & cancer  2013;60(8):10.1002/pbc.24492.
Background
Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited.
Procedure
To assess cardiorespiratory fitness, maximal oxygen uptake (VO2max) was measured in 115 ALL survivors (median age, 23.5 years; range 18–37). We compared VO2max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003–2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest.
Results
Compared to NHANES participants, ALL survivors had a substantially lower VO2max (mean 30.7 vs 39.9 ml/kg/min; adjusted P<0.0001). For any given percent total body fat, ALL survivors had an 8.9 ml/kg/min lower VO2max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2max compared with NHANES participants (all comparisons, P<0.001). Almost two-thirds (66.7%) of ALL survivors were classified as low cardiorespiratory fitness compared with 26.3% of NHANES participants (adjusted P<0.0001). In multivariable models including only ALL survivors, treatment exposures were modestly associated with VO2max. Among females, CRT was associated with low VO2max (P=0.02), but anthracycline exposure was not (P=0.58). In contrast, among males, anthracycline exposure ≥100 mg/m2 was associated with low VO2max (P=0.03), but CRT was not (P=0.54).
Conclusion
Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population.
doi:10.1002/pbc.24492
PMCID: PMC3725590  PMID: 23418044
childhood cancer; acute lymphoblastic leukemia; survivor; cardiorespiratory fitness
13.  The Preventive Health Behaviors of Long-Term Survivors Cancer and Hematopoietic Stem Cell Transplantation Compared to Matched Controls 
BACKGROUND
Little is known about the health promotion, prevention, and disease screening behaviors of cancer survivors treated with hematopoietic cell transplantation (HCT), who undergo arduous treatment and may be at particular risk for late effects and secondary malignancies. The purpose of this study was to examine the current health and secondary prevention behaviors of long-term HCT survivors compared to noncancer matched controls and to identify sociodemographic and clinical factors associated with appropriate prevention practices.
METHODS
HCT survivors (n=662) were drawn from 40 North American transplant centers. Peer-nominated acquaintances of survivors matched on sex, age, education, and marital status, served as controls (n=158). Data were collected a mean of 6.7 years post-HCT (range 1.8 – 22.6 years).
RESULTS
Despite greater frequency of physical exams, HCT survivor health and screening behaviors were similar to matched controls. Sociodemographic factors were associated with health prevention behaviors in expected ways. Some differences between disease group and type of transplant were found, with survivors of acute leukemia less likely to report regular exercise, autologous transplant survivors more likely than allogeneic to report screenings for breast and cervical cancer, and allogeneic survivors more likely than autologous to report a skin exam in the last year.
CONCLUSION
Despite higher levels of engagement with health care providers, HCT survivor health behaviors were no different than matched controls and comparable to those reported by non HCT cancer survivors. There remains considerable room for improvement. These findings support the need for further education of both HCT survivors and health practitioners.
doi:10.1016/j.bbmt.2009.09.015
PMCID: PMC2819641  PMID: 19781657
Cancer; hematopoietic stem cell transplant; bone marrow transplant; health behaviors; cancer survivorship
14.  Estimates of Outcomes Up to Ten Years after Stroke: Analysis from the Prospective South London Stroke Register 
PLoS Medicine  2011;8(5):e1001033.
Charles Wolfe and colleagues collected data from the South London Stroke Register on 3,373 first strokes registered between 1995 and 2006 and showed that between 20% and 30% of survivors have poor outcomes up to 10 years after stroke.
Background
Although stroke is acknowledged as a long-term condition, population estimates of outcomes longer term are lacking. Such estimates would be useful for planning health services and developing research that might ultimately improve outcomes. This burden of disease study provides population-based estimates of outcomes with a focus on disability, cognition, and psychological outcomes up to 10 y after initial stroke event in a multi-ethnic European population.
Methods and Findings
Data were collected from the population-based South London Stroke Register, a prospective population-based register documenting all first in a lifetime strokes since 1 January 1995 in a multi-ethnic inner city population. The outcomes assessed are reported as estimates of need and included disability (Barthel Index <15), inactivity (Frenchay Activities Index <15), cognitive impairment (Abbreviated Mental Test < 8 or Mini-Mental State Exam <24), anxiety and depression (Hospital Anxiety and Depression Scale >10), and mental and physical domain scores of the Medical Outcomes Study 12-item short form (SF-12) health survey. Estimates were stratified by age, gender, and ethnicity, and age-adjusted using the standard European population. Plots of outcome estimates over time were constructed to examine temporal trends and sociodemographic differences. Between 1995 and 2006, 3,373 first-ever strokes were registered: 20%–30% of survivors had a poor outcome over 10 y of follow-up. The highest rate of disability was observed 7 d after stroke and remained at around 110 per 1,000 stroke survivors from 3 mo to 10 y. Rates of inactivity and cognitive impairment both declined up to 1 y (280/1,000 and 180/1,000 survivors, respectively); thereafter rates of inactivity remained stable till year eight, then increased, whereas rates of cognitive impairment fluctuated till year eight, then increased. Anxiety and depression showed some fluctuation over time, with a rate of 350 and 310 per 1,000 stroke survivors, respectively. SF-12 scores showed little variation from 3 mo to 10 y after stroke. Inactivity was higher in males at all time points, and in white compared to black stroke survivors, although black survivors reported better outcomes in the SF-12 physical domain. No other major differences were observed by gender or ethnicity. Increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
Conclusions
Between 20% and 30% of stroke survivors have a poor range of outcomes up to 10 y after stroke. Such epidemiological data demonstrate the sociodemographic groups that are most affected longer term and should be used to develop longer term management strategies that reduce the significant poor outcomes of this group, for whom effective interventions are currently elusive.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, 15 million people have a stroke. About 5 million of these people die within a few days, and another 5 million are left disabled. Stroke occurs when the brain's blood supply is suddenly interrupted by a blood clot blocking a blood vessel in the brain (ischemic stroke, the commonest type of stroke) or by a blood vessel in the brain bursting (hemorrhagic stroke). Deprived of the oxygen normally carried to them by the blood, the brain cells near the blockage die. The symptoms of stroke depend on which part of the brain is damaged but include sudden weakness or paralysis along one side of the body, vision loss in one or both eyes, and confusion or trouble speaking or understanding speech. Anyone experiencing these symptoms should seek immediate medical attention because prompt treatment can limit the damage to the brain. Risk factors for stroke include age (three-quarters of strokes occur in people over 65 years old), high blood pressure, and heart disease.
Why Was This Study Done?
Post-stroke rehabilitation can help individuals overcome the physical disabilities caused by stroke, and drugs and behavioral counseling can reduce the risk of a second stroke. However, people can also have problems with cognition (thinking, awareness, attention, learning, judgment, and memory) after a stroke, and they can become depressed or anxious. These “outcomes” can persist for many years, but although stroke is acknowledged as a long-term condition, most existing data on stroke outcomes are limited to a year after the stroke and often focus on disability alone. Longer term, more extensive information is needed to help plan services and to help develop research to improve outcomes. In this burden of disease analysis, the researchers use follow-up data collected by the prospective South London Stroke Register (SLSR) to provide long-term population-based estimates of disability, cognition, and psychological outcomes after a first stroke. The SLSR has recorded and followed all patients of all ages in an inner area of South London after their first-ever stroke since 1995.
What Did the Researchers Do and Find?
Between 1995 and 2006, the SLSR recorded 3,373 first-ever strokes. Patients were examined within 48 hours of referral to SLSR, their stroke diagnosis was verified, and their sociodemographic characteristics (including age, gender, and ethnic origin) were recorded. Study nurses and fieldworkers then assessed the patients at three months and annually after the stroke for disability (using the Barthel Index, which measures the ability to, for example, eat unaided), inactivity (using the Frenchay Activities Index, which measures participation in social activities), and cognitive impairment (using the Abbreviated Mental Test or the Mini-Mental State Exam). Anxiety and depression and the patients' perceptions of their mental and physical capabilities were also assessed. Using preset cut-offs for each outcome, 20%–30% of stroke survivors had a poor outcome over ten years of follow-up. So, for example, 110 individuals per 1,000 population were judged disabled from three months to ten years, rates of inactivity remained constant from year one to year eight, at 280 affected individuals per 1,000 survivors, and rates of anxiety and depression fluctuated over time but affected about a third of the population. Notably, levels of inactivity were higher among men than women at all time points and were higher in white than in black stroke survivors. Finally, increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
What Do These Findings Mean?
Although the accuracy of these findings may be affected by the loss of some patients to follow-up, these population-based estimates of outcome measures for survivors of a first-ever stroke for up to ten years after the event provide concrete evidence that stroke is a lifelong condition with ongoing poor outcomes. They also identify the sociodemographic groups of patients that are most affected in the longer term. Importantly, most of the measured outcomes remain relatively constant (and worse than outcomes in an age-matched non-stroke-affected population) after 3–12 months, a result that needs to be considered when planning services for stroke survivors. In other words, these findings highlight the need for health and social services to provide long-term, ongoing assessment and rehabilitation for patients for many years after a stroke.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001033.
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); the US National Institute of Health SeniorHealth Web site has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
The UK National Health Service Choices Web site also provides information about stroke for patients and their families
MedlinePlus has links to additional resources about stroke (in English and Spanish)
More information about the South London Stroke Register is available
doi:10.1371/journal.pmed.1001033
PMCID: PMC3096613  PMID: 21610863
15.  Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort 
Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.
Design Retrospective cohort study.
Setting 26 institutions that participated in the Childhood Cancer Survivor Study.
Participants 14 358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.
Main outcome measures Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings.
Results Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m2 or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.
Conclusion Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.
doi:10.1136/bmj.b4606
PMCID: PMC3266843  PMID: 19996459
16.  A Transdiagnostic Community-Based Mental Health Treatment for Comorbid Disorders: Development and Outcomes of a Randomized Controlled Trial among Burmese Refugees in Thailand 
PLoS Medicine  2014;11(11):e1001757.
In a randomized controlled trial, Paul Bolton and colleagues investigate whether a transdiagnostic community-based intervention is effective for improving mental health symptoms among Burmese refugees in Thailand.
Please see later in the article for the Editors' Summary
Background
Existing studies of mental health interventions in low-resource settings have employed highly structured interventions delivered by non-professionals that typically do not vary by client. Given high comorbidity among mental health problems and implementation challenges with scaling up multiple structured evidence-based treatments (EBTs), a transdiagnostic treatment could provide an additional option for approaching community-based treatment of mental health problems. Our objective was to test such an approach specifically designed for flexible treatments of varying and comorbid disorders among trauma survivors in a low-resource setting.
Methods and Findings
We conducted a single-blinded, wait-list randomized controlled trial of a newly developed transdiagnostic psychotherapy, Common Elements Treatment Approach (CETA), for low-resource settings, compared with wait-list control (WLC). CETA was delivered by lay workers to Burmese survivors of imprisonment, torture, and related traumas, with flexibility based on client presentation. Eligible participants reported trauma exposure and met severity criteria for depression and/or posttraumatic stress (PTS). Participants were randomly assigned to CETA (n = 182) or WLC (n = 165). Outcomes were assessed by interviewers blinded to participant allocation using locally adapted standard measures of depression and PTS (primary outcomes) and functional impairment, anxiety symptoms, aggression, and alcohol use (secondary outcomes). Primary analysis was intent-to-treat (n = 347), including 73 participants lost to follow-up. CETA participants experienced significantly greater reductions of baseline symptoms across all outcomes with the exception of alcohol use (alcohol use analysis was confined to problem drinkers). The difference in mean change from pre-intervention to post-intervention between intervention and control groups was −0.49 (95% CI: −0.59, −0.40) for depression, −0.43 (95% CI: −0.51, −0.35) for PTS, −0.42 (95% CI: −0.58, −0.27) for functional impairment, −0.48 (95% CI: −0.61, −0.34) for anxiety, −0.24 (95% CI: −0.34, −0.15) for aggression, and −0.03 (95% CI: −0.44, 0.50) for alcohol use. This corresponds to a 77% reduction in mean baseline depression score among CETA participants compared to a 40% reduction among controls, with respective values for the other outcomes of 76% and 41% for anxiety, 75% and 37% for PTS, 67% and 22% for functional impairment, and 71% and 32% for aggression. Effect sizes (Cohen's d) were large for depression (d = 1.16) and PTS (d = 1.19); moderate for impaired function (d = 0.63), anxiety (d = 0.79), and aggression (d = 0.58); and none for alcohol use. There were no adverse events. Limitations of the study include the lack of long-term follow-up, non-blinding of service providers and participants, and no placebo or active comparison intervention.
Conclusions
CETA provided by lay counselors was highly effective across disorders among trauma survivors compared to WLCs. These results support the further development and testing of transdiagnostic approaches as possible treatment options alongside existing EBTs.
Trial registration
ClinicalTrials.gov NCT01459068
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, one in four people will experience a mental health disorder at some time during their life. Although many evidence-based treatments (EBTs), most involving some sort of cognitive behavioral therapy (talking therapies that help people manage their mental health problems by changing the way they think and behave), are now available, many people with mental health disorders never receive any treatment for their condition. The situation is particularly bad for people living in low-resource settings, where a delivery model for EBTs based on referral to mental health professionals is problematic given that mental health professionals are scarce. To facilitate widespread access to mental health care among poor and/or rural populations in low-resource settings, EBTs need to be deliverable at the primary or community level by non-professionals. Moreover, because there is a large burden of trauma-related mental health disorders in low-resource settings and because trauma increases the risk of multiple mental health problems, treatment options that address comorbid (coexisting) mental health problems in low-resource settings are badly needed.
Why Was This Study Done?
One possible solution to the problem of delivering EBTs for comorbid mental health disorders in low-resource settings is “transdiagnostic” treatment. Many mental health EBTs for different disorders share common components. Transdiagnostic treatments recognize these facts and apply these common components to a range of disorders rather than creating a different structured treatment for each diagnosis. The Common Elements Treatment Approach (CETA), for example, trains counselors in a range of components that are similar across EBTs and teaches counselors how to choose components, their order, and dose, based on their client's problems. This flexible approach, which was designed for delivery by non-professional providers in low-resource settings, provides counselors with the skills needed to treat depression, anxiety, and posttraumatic stress—three trauma-related mental health disorders. In this randomized controlled trial, the researchers investigate the use of CETA among Burmese refugees living in Thailand, many of whom are survivors of decades-long harsh military rule in Myanmar. A randomized controlled trial compares the outcomes of individuals chosen to receive different interventions through the play of chance.
What Did the Researchers Do and Find?
The researchers assigned Burmese survivors or witnesses of imprisonment, torture, and related traumas who met symptom criteria for significant depression and/or posttraumatic stress to either the CETA or wait-list control arm of their trial. Lay counselors treated the participants in the CETA arm by delivering CETA components—for example, “psychoeducation” (which teaches clients that their symptoms are normal and experienced by many people) and “cognitive coping” (which helps clients understand that how they think about an event can impact their feelings and behavior)—chosen to reflect the client's priority problems at presentation. Participants in the control arm received regular calls from the trial coordinator to check on their safety but no other intervention. Participants in the CETA arm experienced greater reductions of baseline symptoms of depression, posttraumatic stress, anxiety, and aggression than participants in the control arm. For example, there was a 77% reduction in the average depression score from before the intervention to after the intervention among participants in the CETA arm, but only a 40% reduction in the depression score among participants in the control arm. Importantly, the effect size of CETA (a statistical measure that quantifies the importance of the difference between two groups) was large for depression and posttraumatic stress, the primary outcomes of the trial. That is, compared to no treatment, CETA had a large effect on the symptoms of depression and posttraumatic stress experienced by the trial participants.
What Do These Findings Mean?
These findings suggest that, among Burmese survivors and witnesses of torture and other trauma living in Thailand, CETA delivered by lay counselors was a highly effective treatment for comorbid mental disorders compared to no treatment (the wait-list control). These findings may not be generalizable to other low-resource settings, they provide no information about long-term outcomes, and they do not identify which aspects of CETA were responsible for symptom improvement or explain the improvements seen among the control participants. Given that the study compared CETA to no treatment rather than a placebo (dummy) or active comparison intervention, it is not possible to conclude that CETA works better that existing treatments. Nevertheless, these findings support the continued development and assessment of transdiagnostic approaches for the treatment of mental health disorders in low-resource settings where treatment access and comorbid mental health disorders are important challenges.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001757.
The World Health Organization provides background information about mental health
The US National Institute of Mental Health provides information about a range of mental health disorders and about cognitive behavioral therapy
The UK National Health Service Choices website has information about cognitive behavioral therapy, including some personal stories and links to other related mental health resources on the Choices website
A short introduction to transdiagnosis and CETA written by one of the trial authors is available
Information about this trial is available on the ClinicalTrials.gov website
The UN Refugee Agency provides information about Burmese (Myanmar) refugees in Thailand
doi:10.1371/journal.pmed.1001757
PMCID: PMC4227644  PMID: 25386945
17.  The association of Ecstasy use and academic achievement among adolescents in two U.S. national surveys 
Addictive behaviors  2008;34(1):9-16.
The association of ecstasy (3, 4-methylenedioxymethamphetamine, MDMA) use with low academic achievement was examined in two nationally representative surveys of adolescents. We tested whether associations with low academic achievement were of similar magnitude or of stronger magnitude for ecstasy versus marijuana use (without ecstasy use), alcohol/tobacco use (without other drug use) and non-drug use in adolescence. Data from the adolescents in the 2002–2005 National Survey of Drug Use and Health (NSDUH, n= 65,294) and from the 2001–2003 Youth Risk Behavior Survey (YRBS, n= 27,592) were analyzed via weighted logistic regression models. Ecstasy, marijuana, and alcohol/tobacco use were associated with moderate and low academic achievement among adolescents in both surveys. Moreover, ecstasy was more strongly associated with low academic achievement and reporting that school gave no grades than alcohol/tobacco in both samples and than marijuana (NSDUH sample only). Prevention programs should inform adolescents that ecstasy use might impair their academic achievement.
doi:10.1016/j.addbeh.2008.07.022
PMCID: PMC2640221  PMID: 18778898
Ecstasy (MDMA) use; Marijuana use; Adolescence; Academic Achievement
18.  Changes in Health Status Among Aging Survivors of Pediatric Upper and Lower Extremity Sarcoma: A Report from the Childhood Cancer Survivor Study (CCSS) 
Objective
To evaluate health status and participation restrictions in childhood extremity sarcoma survivors.
Design
Members of the CCSS cohort with extremity sarcomas, who completed 1995, 2003 or 2007 questionnaires, were included.
Setting
Cohort Study of extremity sarcomas survivors.
Participants
Childhood cancer survivors diagnosed and treated between 1970–1986.
Interventions
Not applicable.
Main Outcome Measure
Prevalence rates for poor health status in six domains and five sub-optimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age.
Results
Among 1094 survivors, median age at diagnosis 13 years (range 0–20), current age 33 years (range 10–53), 49% were male, 87.5% Caucasian, and 75% had lower extremity tumors. In adjusted models, when compared to upper extremity survivors, lower extremity survivors had increased risk of activity limitations but lower risk of not completing college. Compared to those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEA) were 1.6 times more likely to report functional impairment; while those with an above the knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes < $20,000, unemployment and no college degree. Those with UEA more likely reported inactivity, unmarried status and no college degree. Lastly, those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with increased risk of poor mental health, functional impairment and activity limitation.
Conclusion
Treatment for lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at 10% higher risk for not completing college. Type of local control influences health status and participation restrictions. Both these outcomes decline with age.
doi:10.1016/j.apmr.2013.01.013
PMCID: PMC3913046  PMID: 23380347
upper extremity; lower extremity; sarcoma; survivors; childhood cancer
19.  Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St Jude Lifetime Cohort Study 
Journal of Clinical Oncology  2013;31(35):4407-4415.
Purpose
To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).
Patients and Methods
Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.
Results
Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.
Conclusion
This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.
doi:10.1200/JCO.2012.48.2315
PMCID: PMC3842908  PMID: 24190124
20.  Physical, Mental and Neurocognitive Status and Employment Outcomes in the Childhood Cancer Survivor Study Cohort 
Introduction
We examined the relationship of physical, mental, and neurocognitive function with employment and occupational status in the Childhood Cancer Survivor Study.
Methods
We included survivors ≥25 years of age with available Short Form-36 (physical and mental health component scores), Brief Symptom Inventory (depression, anxiety and somatization), and Neurocognitive Questionnaire (task efficiency, emotional regulation, organization, and memory). We generated relative risks (RR) from generalized linear models for these measures on unemployment (N=5386) and occupation (N=3763) outcomes adjusted for demographic and cancer-related factors, and generated sex-stratified models.
Results
Poor physical health was associated with an almost 8-fold higher risk of health-related unemployment (p<0.001) compared to survivors with normal physical health. Male survivors with somatization and memory problems were approximately 50% (p<0.05 for both) more likely to report this outcome, while task efficiency limitations was significant for both sexes (males: RR=2.43, p<0.001; females: RR=2.28, p<0.001). Employed female survivors with task efficiency, emotional regulation, and memory limitations were 13%-20% (p<0.05 for all) less likely to work in professional or managerial occupations than unaffected females.
Conclusions
Physical problems may cause much of the health-related unemployment among childhood cancer survivors. While both male and female survivors with neurocognitive deficits – primarily in task efficiencies – are at risk for unemployment, employed female survivors with neurocognitive deficits may face poor occupational outcomes more often than males.
Impact
Childhood cancer survivors are at risk for poor employment outcomes. Screening and intervention for physical, mental and neurocognitive limitations could improve employment outcomes for this population.
doi:10.1158/1055-9965.EPI-11-0239
PMCID: PMC3266056  PMID: 21844244
pediatric cancer; employment status; physical health; mental health; neurocognitive function
21.  Smokeless and Dual Tobacco Use among Males Surviving Childhood Cancer: A report from the Childhood Cancer Survivor Study 
Cancer survivors experience treatment-related complications that can be exacerbated by tobacco use. This study reports the prevalence of smokeless (ST) and dual tobacco (DT) use, compares these rates to the US population, and examines tobacco risk factors among males surviving childhood cancer. Data from the Childhood Cancer Survivor Study (CCSS) 2007 survey were used (N = 3378). Standardized incidence ratios (SIR) were obtained by comparing CCSS data to the National Survey on Drug Use and Health. Logistic regression was used to evaluate associations between risk factors and tobacco use. Among male survivors, 8.3% and 2.3% were current ST and DT users, respectively. Survivors were less likely than population males to report ST (SIR = 0.64, 95% CI = 0.57 – 0.72) or DT (SIR = 0.37, CI = 0.29 – 0.46) use; however, non-white survivors aged 35–49 years were more likely to use ST (SIR = 2.32, CI = 1.27 – 3.90). ST use was associated (p < 0.05) with younger age at diagnosis, lower education, being married or divorced/separated, and not living in the Northeastern US, while history of cardiovascular- and/or pulmonary-toxic treatment was protective. DT use was associated with younger age at diagnosis, lower education, divorce/separation, and high psychological distress. Having active heart or circulatory conditions was protective. Although ST/DT use is generally low among childhood cancer survivors, these findings suggest that tobacco use screening should be expanded to include ST use and that ST-specific education and cessation interventions should be provided to users. Screening and intervening for ST/DT use in childhood cancer survivors will reduce tobacco-related morbidity and mortality.
doi:10.1158/1055-9965.EPI-12-1302
PMCID: PMC3681858  PMID: 23580700
smokeless tobacco; dual tobacco; cancer survivors; health behaviors
22.  Myeloablative Allogeneic Bone Marrow Transplant Using T Cell Depleted Allografts Followed by Post-Transplant GM-CSF in High Risk Myelodysplastic Syndromes 
Leukemia research  2008;32(9):1439-1447.
Allogeneic blood and marrow transplantation (alloBMT) remains the only curative treatment for patients with myelodysplastic syndromes (MDS), but its application has been limited by the older age range of patients with this disease. T cell depletion decreases transplant-related toxicity related to graft-versus-host disease (GVHD), but does not improve overall survival because of increased risk for relapse and graft failure. Myeloid growth factors have been used to speed engraftment following alloBMT, but data suggest that they may also have anti-tumor properties. We treated 43 patients (median age 56) with MDS/AML with high risk features using a myeloablative T cell depleted alloBMT followed by prolonged systemic GM-CSF. The current event-free survival at 1 and 3 years was 47% and 34% respectively with a median follow-up of 22.8 months in surviving patients. The toxicities compared favorably with those seen using reduced intensity conditioning regimens and included grade III/IV GVHD (10%), graft failure (9%), and cumulative treatment related mortality (28%). The cumulative incidence of relapse remained high at 38%; however, 3/10 patients receiving donor lymphocyte infusions achieved durable complete remissions. These results suggest that it is possible to maintain treatment intensity while minimizing toxicity in older, high-risk MDS patients.
doi:10.1016/j.leukres.2007.12.017
PMCID: PMC2719785  PMID: 18261793
allogeneic bone marrow transplantation; t cell depletion; myelodysplastic syndrome; acute myeloid leukemia; GM-CSF
23.  Partially Mismatched Transplantation and Human Leukocyte Antigen Donor-Specific Antibodies 
The presence of donor human leukocyte antigen (HLA)-specific antibodies (DSA) increases engraftment failure risk in partially HLA-mismatched, or HLA-haploidentical, allogeneic marrow(alloBMT) transplantation. As preexisting sensitization to HLA antigens is not well characterized among candidates for HLA-haploidentical alloBMT, we retrospectively evaluated both the incidence and relative strength of DSA in this patient population. Based on correlations of solid-phase antibody assays on the Luminex (Luminex, Austin, TX) platform with actual crossmatch tests, DSA were characterized as weak for results that were consistent with negative flow cytometric crossmatch results or as moderate-to-strong for results consistent with positive flow cytometric or cytotoxicity crossmatches. We evaluated 296 alloBMT candidates; 111 (37.5%) were female. DSA were detected in 43 (14.5%) candidates, mostly among female candidates (42.9% female versus 12.5% male). Moderate-to-strong DSA strength was more frequently encountered when directed against haploidentical donors as compared with mismatched unrelated donors. DSAwere most commonly detected in female patients directed against their children. Because the presence of DSA has been considered prohibitive for HLA-mismatched alloBMT, we additionally report a desensitization methodology used to reduce DSA to negative or weak levels, ie, levels well below those detectable in a flow cytometric crossmatch. Nine patients without other available donors underwent desensitization. Eight who reduced their DSA to negative or weak levels proceeded to alloBMT and achieved full donor engraftment. These data support routine DSA evaluation in all patients considered for mismatched alloBMT; however, for patients with no other viable options, desensitization to weak or negative DSA levels may afford the opportunity for successful transplantation.
doi:10.1016/j.bbmt.2013.01.016
PMCID: PMC3768172  PMID: 23353119
Donor specific antibodies; Haploidentical allogeneic bone marrow transplantation; Desensitization
24.  High-Dose Cytarabine in Acute Myeloid Leukemia Treatment: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(10):e110153.
The optimal dose, scheme, and clinical setting for Ara-C in acute myeloid leukemia (AML) treatment remain uncertain. In this study, we performed a meta-analysis to systematically assess the impact of high-dose cytarabine (HDAC) on AML therapy during the induction and consolidation stages. Twenty-two trials with a total of 5,945 de novo AML patients were included in the meta-analysis. Only patients less than 60 year-old were included in the study. Using HDAC in induction therapy was beneficial for RFS (HR = 0.57; 95% CI, 0.35–0.93; P = 0.02) but not so for CR rate (HR = 1.01; 95% CI, 0.93–1.09; P = 0.88) and OS (HR = 0.83; 95% CI, 0.66–1.03; P = 0.1). In consolidation therapy, HDAC showed significant RFS benefits (HR = 0.67; 95% CI, 0.49–0.9; P = 0.008) especially for the favorable-risk group (HR = 0.38; 95% CI, 0.21–0.69; P = 0.001) compared with SDAC (standard dose cytarabine), although no OS advantage was observed (HR = 0.84; 95% CI, 0.55–1.27; P = 0.41). HDAC treatment seemed less effective than auto-BMT/allo-BMT treatment (HR = 1.66, 95% CI, 1.3–2.14; P<0.0001) with similar OS. HDAC treatment led to lower relapse rate in induction and consolidation therapy than SDAC treatment, especially for the favorable-risk group. Auto-BMT/allo-BMT was more beneficial in prolonging RFS than HDAC.
doi:10.1371/journal.pone.0110153
PMCID: PMC4192550  PMID: 25299623
25.  Early outreach to survivors of the shootings in Norway on the 22nd of July 2011 
European Journal of Psychotraumatology  2014;5:10.3402/ejpt.v5.23523.
Background
Under-treatment and unmet needs among survivors have been documented years after terror attacks. Improved early and proactive outreach strategies, including targeted interventions for individuals in need, are required. After the terrorist attacks in Norway on 22 July 2011, a national, proactive outreach strategy was developed and implemented to help those who were directly affected.
Objectives
The aims of this study were threefold: (1) to investigate whether the survivors at the island of Utøya had received proactive outreach from the municipalities, (2) to examine the relationships between received health services and the survivors’ level of exposure and post-trauma health problems, and (3) to explore the level of unmet needs among survivors 5 months post-terror.
Methods
Three hundred and twenty five survivors (M age=19.4, SD=4.6, 47.1% females, response rate 66%) of the 2011 massacre on Utøya Island, Norway, were interviewed face-to-face 4–5 months post-terror. The survivors were asked if they had received proactive outreach from their municipality, and what type of health services they had received. Survivors’ level of peri-trauma exposure, loss and injury, posttraumatic stress reactions, symptoms of anxiety and depression, somatic health problems, and sick leave, were assessed.
Results
Most participants (87%) reported that they had received early and proactive outreach, and most (84%) had a contact person. In addition a majority of the survivors has received support from their general practitioner (63%), or other municipal help services (66%). Specialized mental health services by psychiatrists or psychologists had been provided to 73.1% of the survivors. Survivors who had been referred to specialized mental health services reported higher levels of exposure to trauma, posttraumatic stress reactions, depression and anxiety, and somatic health problems, compared to non-receivers of such services. Forty-three survivors (14%) reported unmet needs for services.
Conclusion
In accordance with the national strategy, the vast majority of the participants in this study had received an early and proactive outreach and targeted responses from specialized mental health services had been provided to survivors in need of more extensive help. However, an important minority of the participants had not been reached as planned. The knowledge from this study may guide professionals and decision makers in planning for future disasters and improve the levels of care.
doi:10.3402/ejpt.v5.23523
PMCID: PMC4082194  PMID: 25018858
Posttraumatic stress reactions; PTSD; youth; terror; shootings; early intervention

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