We prospectively investigated whether coffee consumption was associated with decreased risk of colorectal cancer and whether cigarette smoking and stage of disease modify the association in the Singapore Chinese Health Study. During the first 12 years of follow-up, 961 colorectal cancer cases occurred in the cohort of over 60,000 middle-aged or older Chinese men and women living in Singapore. Baseline dietary exposures were assessed through in-person interviews using a validated food frequency questionnaire. The relation between coffee consumption and colorectal cancer risk was assessed by proportional hazards (Cox) regression. No overall association between coffee intake and colorectal cancer was observed. However, in analysis by subsite and stage restricted to ever smokers, the coffee–colon cancer association became statistically significant for advanced disease (P for trend = 0.01). The hazard ratio was 0.56 (95% confidence interval = 0.35–0.90) for advanced colon cancer in drinkers of 2 or more cups per day compared with those who drank no coffee or less than 1 cup per day. Although there is a null association between coffee intake and risk of colorectal cancer overall, coffee may protect against smoking related advanced colon cancer.

Purpose

Although health disparities are well-described for many cancers, little is known about racial and ethnic disparities in neuroblastoma. To evaluate differences in disease presentation and survival by race and ethnicity, data from the Children's Oncology Group (COG) were analyzed.

Patients and Methods

The racial/ethnic differences in clinical and biologic risk factors, and outcome of patients with neuroblastoma enrolled on COG ANBL00B1 between 2001 and 2009 were investigated.

Results

A total of 3,539 patients (white, 72%; black, 12%; Hispanic, 12%; Asian, 4%; and Native American, < 1%) with neuroblastoma were included. The 5-year event-free survival (EFS) rates were 67% for whites (95% CI, 65% to 69%), 69% for Hispanics (95% CI, 63% to 74%), 62% for Asians (95% CI, 51% to 71%), 56% for blacks (95% CI, 50% to 62%), and 37% for Native American (95% CI, 17% to 58%). Blacks (P < .001) and Native Americans (P = .04) had a higher prevalence of high-risk disease than whites, and significantly worse EFS (P = .01 and P = .002, respectively). Adjustment for risk group abrogated these differences. However, closer examination of the EFS among high-risk patients who remained event free for 2 years or longer, revealed a higher prevalence of late-occurring events among blacks compared with whites (hazard ratio, 1.5; 95% CI, 1.0 to 2.3; P = .04).

Conclusion

Black and Native American patients with neuroblastoma have a higher prevalence of high-risk disease, accounting for their worse EFS when compared with whites. The higher prevalence of late-occurring events among blacks with high-risk disease suggests that this population may be more resistant to chemotherapy. Studies focused on delineating the genetic basis for the racial disparities observed in this study are planned.

Purpose

Hispanics have a higher risk of early post-HCT treatment failure when compared to non-Hispanic whites. However, long-term morbidity among Hispanics has not been described.

Patients and Methods

Health-related outcomes were examined in 159 Hispanic and 825 non-Hispanic white patients who had undergone HCT between 1974 and 1998 and survived a mean of 8.7 years. Patients completed a detailed questionnaire about sociodemographic factors and the occurrence of chronic health conditions.

Results

Exposure to total body irradiation (TBI: OR=1.94, 95%CI, 1.06–3.56, p=0.03), presence of chronic graft vs. host disease (GvHD: OR=3.99, 95% CI, 1.94–8.24, p=0.002), and health insurance coverage (OR=3.46, 95% CI, 1.5–8.01, p=0.004), were significantly associated with severe/life-threatening conditions. Compared to non-Hispanic whites, Hispanics were 53% less likely to report severe/life-threatening conditions (OR=0.47, 95%CI, 0.27–0.83, p=0.009) after adjusting for relevant clinical variables. This effect size was mitigated (OR=0.56 [95%CI, 0.29–1.08], p=0.08) after adjusting for health insurance coverage.

Conclusions

Hispanics are less likely to report severe/life-threatening health conditions after HCT than non-Hispanic whites – a difference that decreases in magnitude and significance after taking health insurance into consideration. While confirming the role of TBI, and chronic GvHD, this study identifies the role of lack of health insurance coverage as a mediator of the lower prevalence of self-reported long-term morbidity in Hispanics.

Long-term survival after hematopoietic cell transplantation (HCT) is now an expected outcome. The growing population of survivors is at risk of developing treatment-related complications, including cardiovascular events (CVD). A nested case-control design was used to identify clinical and treatment-related risk factors for development of late (1+ years after HCT) CVD. Cases were identified from a cohort of one+ year survivors transplanted at City of Hope between 1977 and 2006. Controls (HCT survivors without CVD) were matched on age, year of HCT, type of HCT, and length of follow-up. Sixty-three patients with late CVD were identified; 44 (69.8%) with coronary artery events, and 19 (30.2%) with cerebrovascular events. Median age at HCT was 49.0 years; median age at late CVD was 54.0 years; 66.7% had undergone autologous HCT. Multivariate logistic regression analysis revealed multiple cardiovascular risk factors (≥2 of the following: obesity, dyslipidemia, hypertension, and diabetes) after HCT to be associated with a 5.2-fold increased risk of late CVD (p<0.01); pre-HCT chest radiation was associated with a 9.5-fold risk of coronary artery disease (p=0.03). Pre-HCT exposure to chest radiation and presence of comorbidities are primarily responsible for the risk associated with late CVD after HCT. These data form the basis for developing predictive models for identifying high-risk individuals for targeted surveillance and aggressive management of comorbidities.

The Bone Marrow Transplant Survivor Study is a retrospective cohort study in which participants who received HCT between 1974–1998 and survived for ≥2 yr completed a 255 item questionnaire on late effects occurring after HCT. There were 281 survivors with AML and 120 with ALL. Siblings of participants (n=319) were recruited for comparison. Median age at interview was 36.5 yr for survivors and 44yr for siblings. Median follow-up after HCT was 8.4 yr. Conditioning included TBI in 86% of AML and 100% of ALL subjects. The frequencies of late effects did not differ between ALL and AML survivors. Compared to siblings, survivors had a higher frequency of diabetes, hypothyroidism, osteoporosis, exercise induced shortness of breath (EISB), neurosensory impairments, and problems with balance, tremor or weakness. In multivariable analysis, the risk of these outcomes did not differ by diagnosis. Survivors after allogeneic HCT had higher odds of diabetes (odds ratio [OR] 3.9, p=0.04), osteoporosis (OR 3.1, p=0.05), abnormal sense of touch (OR 2.6, p=0.02) and to report their overall health as fair or poor (OR 2.2, p=0.03). Ongoing surveillance for these late effects and appropriate interventions are required to improve the health status of ALL and AML survivors after HCT.

Avascular necrosis (AVN) is a debilitating condition reported after chronic steroid use. The purpose of this study was to describe the magnitude of risk in individuals who survived one or more years after hematopoietic cell transplantation (HCT), and to investigate the role of immunosuppressive agents such as prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and cyclosporine (CSA) in the development of AVN after HCT. Using a retrospective study design, we followed 1,346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and relapse. Cox proportional regression techniques were used to identify associated risk factors. The median age at HCT was 34 years (range, 7 months–69 years), and median length of follow-up for those alive was 8.2 years. Seventy-five patients developed AVN of 160 joints. The cumulative incidence of AVN at 10 years was 2.9% after autologous HCT, 5.4% after allogeneic matched related donor HCT, and 15% after unrelated donor HCT (p<0.001 compared to autologous HCT recipients). For allogeneic transplant recipients, male sex (RR=2.1, 95% CI, 1.1–4.0), presence of chronic GvHD (RR=2.2) and exposure to CSA, FK506, prednisone and MMF rendered patients at increased risk, especially in patients with a history of exposure to three or more drugs (RR=9.2, 95%CI, 2.42–35.24). Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition.

Purpose

Therapy-related myelodysplasia or acute myelogenous leukemia (t-MDS/AML) is a lethal complication of autologous hematopoietic stem-cell transplantation (aHCT) for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). Here, we investigated the hypothesis that accelerated telomere shortening after aHCT could contribute to the development of t-MDS/AML.

Patients and Methods

A prospective longitudinal cohort was constructed to investigate the sequence of cellular and molecular abnormalities leading to development of t-MDS/AML after aHCT for HL/NHL. This cohort formed the sampling frame for a nested case-control study to compare changes in telomere length in serial blood samples from patients who developed t-MDS/AML with matched controls who did not develop t-MDS/AML.

Results

An initial increase in telomere length at day 100 after aHCT was followed by an accelerated telomere shortening in t-MDS/AML patients when compared with controls. These telomere alterations preceded the onset of t-MDS and were independent of other known risk factors associated with development of t-MDS/AML on multivariate analysis. Additionally, we observed reduced generation of committed progenitors in patients who developed t-MDS/AML, indicating that these telomere alterations were associated with reduced regenerative capacity of hematopoietic stem cells.

Conclusion

The development of t-MDS/AML after aHCT is associated with and preceded by markedly altered telomere dynamics in hematopoietic cells. Accelerated telomere loss in patients developing t-MDS/AML may reflect increased clonal proliferation and/or altered telomere regulation in premalignant cells. Genetic instability associated with shortened telomeres may contribute to leukemic transformation in t-MDS/AML.

Purpose

To examine the independent roles of pre–hematopoietic cell transplantation (HCT) therapeutic exposures, transplantation-related conditioning, and comorbidities (pre- and post-HCT) in the development of late congestive heart failure (CHF) after HCT.

Methods

This was a nested case-control design. Individuals with late CHF (diagnosed ≥ 1 year after HCT) were identified from a cohort of 2,938 1+ year survivors who underwent transplantation at City of Hope National Medical Center, Duarte, CA. This cohort formed the sampling frame for selecting controls (without CHF) matched for age and year of HCT, donor source (allogeneic v autologous), and length of follow-up.

Results

Sixty patients with late CHF were identified; median age at HCT was 45.3 years (range, 16.6 to 68.6 years); median time to CHF was 3.0 years (range, 1.03 to 18.9 years); 68% received autologous HCT. Median ejection fraction was 36.9% (range, 15% to 53%). Compared with matched controls (n = 166), patients with late CHF received more cycles of pre-HCT chemotherapy (8.6 v 4.9 cycles; P < .01), had greater body mass index at HCT (28.4 v 26.2 kg/m2; P = .01), greater lifetime anthracycline exposure (285.3 v 175.6 mg/m2; P < .01), and were more likely to have multiple chronic comorbidities (30.0% v 13.9%; P < .01). Multivariable analysis revealed number of pre-HCT chemotherapy cycles (odds ratio [OR] = 1.2; P < .01), anthracycline dose ≥ 250 mg/m2 (OR = 3.2; P = .05), and two or more chronic comorbidities (OR = 4.3; P = .01) to be independently associated with late CHF.

Conclusion

Pre-HCT exposure to anthracyclines and presence of comorbidities are primarily responsible for the risk associated with late CHF after HCT. Conditioning-related therapeutic exposure does not contribute significantly to the risk. These results form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities.

Background

Long-term HCT survivors have a high prevalence of severe and chronic health conditions, placing significant demands on the healthcare system. The aim of this study was to evaluate and compare the healthcare utilization by adult Hispanic and non-Hispanic white long term survivors of HCT.

Methods

A mailed questionnaire was used to assess self-reported health care utilization in three domains: general contact with healthcare system, general physical examination outside cancer center (GPE), and Cancer/HCT center visit. Eligible individuals had undergone HCT between 1974 and 1998, at 21 years of age or older and survived 2 or more years after HCT.

Results

The cohort included 681 non-Hispanic white and 137 Hispanic survivors. The median age at HCT was 38.3 years and the median length of follow-up was 6.6 years. Hispanic survivors had lower family income and education and were more likely to lack health insurance. The prevalence of GPE increased significantly over time among non- Hispanic whites (67% at 2–5 years to 76% at 11+ years) but remained unchanged among Hispanics (66% to 61%). Cancer/ HCT center visits declined over time among both Hispanics and non-Hispanic whites but higher proportion of Hispanics reported Cancer/HCT center visit at 11+ years after HCT (81% vs. 54%).

Conclusion

As compared to non-Hispanic whites, Hispanic survivors are less likely to establish contact with a primary care providers years after the HCT and continue to receive care at Cancer/HCT center. Future studies of this population are needed to establish the factors responsible for this pattern of healthcare utilization.

This study describes the risk of delayed chronic kidney disease (CKD) in 1190 adult hematopoietic cell transplantation (HCT) survivors who underwent HCT for hematologic malignancies or aplastic anemia between 1976 and 1997, and survived at least one year. CKD was defined as a sustained elevation of serum creatinine inferring a glomerular filtration rate of <60 mL/min/1.73 m2 for three months or longer. Median age at HCT was 35.0 years (range, 18.1 to 68.6 years) and median length of follow-up, 7.1 years from HCT (range, 1 to 24.3 years). Sixty patients with CKD were identified, resulting in a cumulative incidence of 4.4% at 5 years (autologous HCT: 3.8%; matched sibling HCT: 4.5%; unrelated donor HCT: 10.0%; p=0.09 compared to autologous HCT). Older age at HCT (relative risk [RR] per five-year increment, 1.33; 95% CI, 1.2-1.5); exposure to cyclosporine without tacrolimus (RR=1.90, 95% CI, 1.1 to 3.4) or with tacrolimus (RR=4.59, 95% CI, 1.8 to 11.5); and a primary diagnosis of multiple myeloma (RR=2.51, 95% CI, 1.1 to 5.6) were associated with an increased risk of delayed CKD. This study identifies sub-populations of HCT at increased risk for CKD, setting the stage for appropriate long-term follow-up of vulnerable patients.

We determined the prevalence of self-reported late-effects in survivors of autologous hematopoietic-cell transplantation (HCT) for Hodgkin’s lymphoma (HL, n=92) and non-Hodgkin’s lymphoma (NHL, n=184) using a 255-item questionnaire and compared them to 319 sibling controls in the Bone Marrow Transplant Survivor Study. Median age at HCT was 39 years (range, 13-69) and median post-transplant followup was 6 years (range, 2-17). Median age at survey was 46 years (range, 21-73) for survivors and 44 years (range, 19-79) for siblings. Compared to siblings, HCT survivors reported a significantly higher frequency of cataracts, dry mouth, hypothyroidism, bone impairments (osteoporosis and avascular necrosis), congestive heart failure, exercise-induced shortness of breath, neurosensory impairments, inability to attend work or school and poor overall health. Compared to those receiving no total-body irradiation (TBI), patients treated with TBI-based conditioning had higher risks of cataracts (odds-ratio (OR) 4.9, 95%CI 1.5-15.5) and dry mouth (OR 3.4, 95%CI 1.1-10.4). Females had a greater likelihood of reporting osteoporosis (OR 8.7, 95%CI: 1.8-41.7), congestive heart failure (OR 4.3, 95%CI 1.1-17.2) and abnormal balance, tremor or weakness (OR 2.4, 95%CI 1.0-5.5). HL and NHL survivors of autologous HCT have a high prevalence of long-term health-related complications and require continued monitoring for late-effects of transplantation.