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ABSTRACT: Long-term morbidity after hematopoietic cell transplantation (HCT) is unknown. The risk of physical and psychological health in 324 patients who had survived 10 or more years after HCT, and a sibling comparison group (n=309) was evaluated. Using the CTCAE v3.0, the 15-year cumulative incidence of severe/life-threatening/fatal conditions was 41% (95%CI, 34-48%). HCT survivors were 5.7 times as likely to develop a severe/life-threatening condition (p<0.001), and 2.7 times as likely to report somatic distress (p<0.001) compared with siblings. Compared with allogeneic HCT recipients with no chronic GvHD, those with active chronic GvHD were at a 1.8-fold higher risk of severe/life-threatening health conditions (p=0.006), and 4.5-fold higher risk of somatic distress (p=0.04); allogeneic HCT recipients with resolved chronic GvHD were not at increased risk of morbidity compared with those with no chronic GvHD. Only 27% of the HCT survivors returned to the transplant center for their cancer-related care. The burden of long-term physical and emotional morbidity borne by survivors remains substantial, even beyond 10 years after HCT; however, specialized healthcare is underutilized. Patients, families and healthcare providers need to be made aware of the high burden, such that they can plan for post-HCT care, even many years after HCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2013; · 3.15 Impact Factor
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Amrita Y Krishnan,
Matthew Mei, Can-Lan Sun,
Sandra H Thomas,
Jennifer Berano Teh,
Tongjun Kang,
Myo Htut,
George Somlo,
Firoozeh Sahebi,
Stephen J Forman,
Smita Bhatia
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ABSTRACT: Recent studies demonstrate an increased risk of second primary malignancies (SPM) in multiple myeloma (MM) patients on maintenance lenalidomide following autologous stem cell transplantation (ASCT). There may be other risk factors driving SPM post-ASCT in MM, so we explored this possibility through analysis of our large transplant database in conjunction with our long-term followup program. We conducted a retrospective cohort study of 841 consecutive MM patients who underwent ASCT from 1989-2009 at City of Hope, as well as a nested case-control analysis evaluating the role of all therapeutic exposures before, during and after ASCT. Median length of follow-up for the entire cohort was 3.4 years (range 0.3-19.9). Sixty cases with seventy SPM were identified. The overall cumulative incidence of SPM was 7.4% at five years and 15.9% at ten years if non-melanoma skin cancers (NMSCs) were included, and 5.3% at 5 years and 11.2% at 10 years if NMSCs were excluded. Multivariate analysis of the entire cohort revealed association of both older age (≥55yrs) (RR 2.3 p<0.004) and race (non-Hispanic white) (RR 2.4 p=0.01) with an increased risk of SPM. Furthermore, thalidomide exposure demonstrated a trend towards increased risk (OR=3.5, p=0.15); however, not enough patients were treated with lenalidomide to accurately assess the risk of this agent. Exclusion of NMSCs retained the association with these variables, but was accompanied with loss of statistical significance. This large single-institution analysis identified race and older age to be associated with increased risk of developing SPM. The trend toward increased risk with thalidomide exposure suggests a class effect from immunomodulatory drugs that may not be restricted to lenalidomide.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2012; · 3.15 Impact Factor
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Saro H Armenian, Can-Lan Sun,
Tabitha Vase,
Kirsten K Ness,
Emily Blum,
Liton Francisco,
Kalyanasundaram Venkataraman,
Raynald Samoa,
F Lennie Wong,
Stephen J Forman,
Smita Bhatia
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ABSTRACT: HCT recipients may be at an increased risk of developing hypertension, diabetes and dyslipidemia (referred to as cardiovascular risk factors ([CVRFs]); and these can potentially increase the risk of cardiovascular disease (CVD). We examined the incidence and predictors of CVRFs and subsequent CVD in 1885 consecutive 1+year survivors of HCT performed at City of Hope between 1995 and 2004. Ten-year cumulative incidence (CI) of hypertension, diabetes, dyslipidemia, and multiple (≥2) CVRFs was 37.7%, 18.1%, 46.7%, and 31.4%, respectively. The prevalence of CVRFs was significantly higher among HCT recipients compared to the general population; contributed to largely by allogeneic HCT recipients. Older age and obesity at HCT were associated with increased risk of CVRFs. History of Grade II-IV acute graft versus host disease was associated with an increased risk for hypertension (RR=9.1, p<0.01), diabetes (RR=5.8, p<0.01) and dyslipidemia (RR=3.2, p<0.01); conditioning with total body irradiation was associated with an increased risk of diabetes (RR=1.5, p=0.01) and dyslipidemia (RR=1.4, p<0.01). There was an incremental increase in 10-year incidence of CVD by number of CVRFs (4.7% [none], 7.0% [1 CVRF], 11.2% [≥2 CVRFs], p<0.01); the risk was especially high (15.0%) in patients with multiple CVRFs and pre-HCT exposure to anthracyclines or chest radiation.
Blood 10/2012; · 9.90 Impact Factor
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ABSTRACT: Chromosomal aberrations are an important consequence of genotoxic exposure and contribute to pathogenesis and progression of several malignancies. We investigated the susceptibility to chromosomal aberrations in chronic myelogenous leukemia (CML) progenitors after exposure to ionizing radiation. In normal progenitors, ionizing radiation induced both stable and unstable chromosomal lesions, but only stable aberrations persisted after multiple divisions. In contrast, radiation of chronic phase CML progenitors resulted in enhanced generation of unstable lesions that persisted after multiple divisions. CML progenitors demonstrated active cell cycle checkpoints and increased nonhomologous end joining DNA repair, suggesting that persistence of unstable aberrations was the result of continued generation of these lesions. CML progenitors demonstrated enhanced susceptibility to repeated cycles of chromosome damage, repair, and damage through a breakage-fusion-bridge mechanism. Perpetuation of breakage-fusion-bridge cycles in CML progenitors was mediated by classic nonhomologous end joining repair. These studies reveal a previously unrecognized mechanism of chromosomal instability in leukemia progenitors because of continued generation of unstable chromosomal lesions through repeated cycles of breakage and repair of such lesions.
Blood 04/2012; 119(26):6187-97. · 9.90 Impact Factor
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ABSTRACT: Advances in autologous hematopoietic cell transplantation (HCT) strategies have resulted in a growing number of long-term survivors. However, these survivors are at increased risk of developing cardiovascular complications due to pre-HCT therapeutic exposures and conditioning and post-HCT comorbidities. We examined the incidence and predictors of congestive heart failure (CHF) in 1244 patients undergoing autologous HCT for a hematologic malignancy between 1988 and 2002. The cumulative incidence of CHF was 4.8% at 5 years and increased to 9.1% at 15 years after transplantation; the CI for female lymphoma survivors was 14.5% at 15 years. The cohort was at a 4.5-fold increased risk of CHF (standardized incidence ratio = 4.5), compared with the general population. The risk of CHF increased substantially for patients receiving ≥ 250 mg/m(2) of cumulative anthracycline exposure (odds ratio [OR]: 9.9, P < .01), creating a new and lower threshold for cardiac surveillance after HCT. The presence of hypertension among recipients of high-dose anthracycline (≥ 250 mg/m(2)) resulted in a 35-fold risk (OR: 35.3, P < .01) of CHF; the risk was nearly 27-fold (OR: 26.8, P < .01) for high-dose anthracycline recipients with diabetes, providing evidence that hypertension and diabetes may be critical modifiers of anthracycline-related myocardial injury after HCT and creating targeted populations for aggressive intervention.
Blood 12/2011; 118(23):6023-9. · 9.90 Impact Factor
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Javier G Blanco, Can-Lan Sun,
Wendy Landier,
Lu Chen,
Diego Esparza-Duran,
Wendy Leisenring,
Allison Mays,
Debra L Friedman,
Jill P Ginsberg,
Melissa M Hudson,
Joseph P Neglia,
Kevin C Oeffinger,
A Kim Ritchey,
Doojduen Villaluna,
Mary V Relling,
Smita Bhatia
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ABSTRACT: Carbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single nucleotide polymorphisms in CBR1 (CBR1 1096G>A) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors.
One hundred seventy survivors with cardiomyopathy (patient cases) were compared with 317 survivors with no cardiomyopathy (controls; matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity) using conditional logistic regression techniques.
A dose-dependent association was observed between cumulative anthracycline exposure and cardiomyopathy risk (0 mg/m(2): reference; 1 to 100 mg/m(2): odds ratio [OR], 1.65; 101 to 150 mg/m(2): OR, 3.85; 151 to 200 mg/m(2): OR, 3.69; 201 to 250 mg/m(2): OR, 7.23; 251 to 300 mg/m(2): OR, 23.47; > 300 mg/m(2): OR, 27.59; P(trend) < .001). Among individuals carrying the variant A allele (CBR1:GA/AA and/or CBR3:GA/AA), exposure to low- to moderate-dose anthracyclines (1 to 250 mg/m(2)) did not increase the risk of cardiomyopathy. Among individuals with CBR3 V244M homozygous G genotypes (CBR3:GG), exposure to low- to moderate-dose anthracyclines increased cardiomyopathy risk when compared with individuals with CBR3:GA/AA genotypes unexposed to anthracyclines (OR, 5.48; P = .003), as well as exposed to low- to moderate-dose anthracyclines (OR, 3.30; P = .006). High-dose anthracyclines (> 250 mg/m(2)) were associated with increased cardiomyopathy risk, irrespective of CBR genotype status.
This study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m(2). Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low- to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.
Journal of Clinical Oncology 11/2011; 30(13):1415-21. · 18.37 Impact Factor
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ABSTRACT: Little information exists regarding long-term psychological health of hematopoietic cell transplantation (HCT) survivors. Using resources offered by the Bone Marrow Transplant Survivor Study (BMTSS), we evaluated adverse psychological outcomes in 1065 long-term HCT survivors and a healthy comparison group composed of siblings. Psychological health status was evaluated using the Brief Symptom Inventory-18. Twenty-two percent of the HCT survivors reported adverse psychological outcomes, compared with 8% of the siblings. Exposure to prednisone was associated with psychological distress across all domains (anxiety, depression, and somatic distress). Fifteen percent of the HCT survivors reported somatic distress, representing an almost 3-fold higher risk comparing to siblings. Among survivors, in addition to low annual household income and self-reported poor health, having severe/life-threatening conditions and presence of active chronic GVHD were associated with a 2-fold increased risk for somatic distress. Seven percent of the HCT survivors expressed suicidal ideation; patients with higher scores on depression subscale were most vulnerable. This study demonstrates that somatic distress is the biggest challenge faced by survivors long after HCT. These results identify vulnerable subpopulations and provide patients, families, and healthcare providers with necessary information to plan for post-HCT needs many years after HCT.
Blood 08/2011; 118(17):4723-31. · 9.90 Impact Factor
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Saro H Armenian, Can-Lan Sun,
Toana Kawashima,
Mukta Arora,
Wendy Leisenring,
Charles A Sklar,
K Scott Baker,
Liton Francisco,
Jennifer Berano Teh,
George Mills,
F Lennie Wong,
Joseph Rosenthal,
Lisa R Diller,
Melissa M Hudson,
Kevin C Oeffinger,
Stephen J Forman,
Leslie L Robison,
Smita Bhatia
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ABSTRACT: HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.
Blood 06/2011; 118(5):1413-20. · 9.90 Impact Factor
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ABSTRACT: 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.
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).
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.
Journal of Clinical Oncology 01/2011; 29(1):76-82. · 18.37 Impact Factor
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ABSTRACT: An elevated serum α-fetoprotein (AFP) level before orthotopic liver transplant (OLT) is predictive of mortality after OLT for hepatocellular carcinoma (HCC).
Retrospective analysis of a population-based cohort.
United Network for Organ Sharing registry (2003-2008).
We identified 2253 patients who underwent OLT for HCC with available pre-OLT serum AFP values.
Patients were stratified by AFP levels into low (<20 ng/mL), medium (20-399 ng/mL), or high (≥400 ng/mL) groups. Clinical and pathological characteristics were compared among groups. Survival curves were constructed by the Kaplan-Meier method, and univariate and multivariate Cox-regression analysis was performed.
Of the 2253 patients, 1210 (53.7%), 805 (35.7%), and 238 (10.6%) were in the low, medium, and high AFP groups, respectively. On univariate analysis, the low AFP group demonstrated the best 4-year survival (76%) compared with the medium (65%; P = .001) and high (57%; P < .001) AFP groups. When AFP levels in patients with only stage II HCC underwent assessment, improved survival in the low AFP group was still observed (P < .001). On multivariate analysis, the medium and high AFP groups were associated with higher mortality (hazard ratios, 1.50 [95% confidence interval, 1.19-1.89; P = .001] and 2.11 [1.55-2.88; P < .001], respectively).
Serum AFP level is an independent prognostic predictor of outcome after OLT for HCC. The association between serum AFP value and post-OLT survival warrants further investigation to potentially better allocate donor allografts for HCC.
Archives of surgery (Chicago, Ill.: 1960) 01/2011; 146(1):26-33. · 4.32 Impact Factor
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ABSTRACT: Long-term survival is now an expected outcome after hematopoietic cell transplantation (HCT). However, the burden of morbidity long-term after HCT remains unknown. We examined the magnitude of risk of chronic health conditions reported by 1022 HCT survivors and their siblings (n = 309). A severity score (grades 1 [mild] through 4 [life-threatening]) was assigned to each health condition using the Common Terminology Criteria for Adverse Events, Version 3. Sixty-six percent of the HCT survivors reported at least one chronic condition; 18% reported severe/life-threatening conditions; comparable values in siblings were 39% and 8%, respectively (P < .001). The cumulative incidence of a chronic health condition among HCT survivors was 59% (95% confidence interval [CI], 56%-62%) at 10 years after HCT; for severe/life-threatening conditions or death from chronic health conditions, the 10-year cumulative incidence approached 35% (95% CI, 32%-39%). HCT survivors were twice as likely as siblings to develop a chronic condition (95% CI, 1.6-2.1), and 3.5 times to develop severe/life-threatening conditions (95% CI, 2.3-5.4). HCT survivors with chronic graft-versus-host disease were 4.7 times as likely to develop severe/life-threatening conditions (95% CI, 3.0-7.2). The burden of long-term morbidity borne by HCT survivors is substantial, and long-term follow-up of patients who received transplantation is recommended.
Blood 10/2010; 116(17):3129-39; quiz 3377. · 9.90 Impact Factor
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ABSTRACT: Hispanics have a greater risk of early treatment failure after hematopoietic stem cell transplantation (HCT) compared with non-Hispanic whites. However, long-term morbidity among Hispanics has not been described.
Health-related outcomes were examined in 159 Hispanic patients and 825 non-Hispanic white patients who underwent 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.
Exposure to total body irradiation (TBI) (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.06-3.56; P = .03), the presence of chronic graft versus host disease (GvHD) (OR, 3.99; 95% CI, 1.94-8.24; P = .002), and health insurance coverage (OR, 3.46; 95% CI, 1.5-8.01; P = .004), were associated significantly with severe/life-threatening conditions. Compared with non-Hispanic white patients, Hispanic patients were 53% less likely to report severe/life-threatening conditions (OR, 0.47; 95% CI, 0.27-0.83; P = .009) after adjusting for relevant clinical variables. This effect size was mitigated (OR, 0.56; 95%CI, 0.29-1.08; P = .08) after adjusting for health insurance coverage.
Hispanics were less likely to report severe/life-threatening health conditions after HCT than non-Hispanic whites-a difference that decreased in magnitude and significance after taking health insurance into consideration. Although the current results confirmed the role of TBI and chronic GvHD, in the current study, the role of a lack of health insurance coverage was identified as a mediator of the lower prevalence of self-reported long-term morbidity in Hispanics.
Cancer 09/2010; 116(17):4152-9. · 4.77 Impact Factor
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ABSTRACT: Racial, ethnic, and socioeconomic disparities in the survival of patients with hepatocellular carcinoma (HCC) continue to exist. The authors of this report hypothesized that these differences result from inequities in access to care and in response to therapy.
Patients with HCC (n = 20,920) were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients who underwent liver transplantation for HCC (n = 4735) were identified from the United Network for Organ Sharing (UNOS) database. Clinical and pathologic factors were compared after patients were stratified by race and ethnicity.
The survival of patients with HCC improved over time for all racial, ethnic, and income groups (P < .001). Black and low income individuals had the poorest long-term survival (P < .001). On multivariate analysis, black race was predictive of the poorest survival (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.09-1.22; P < .001), whereas Asian race was associated with the best survival (HR, 0.87; 95% CI, 0.83-0.91; P < .001). After liver transplantation, black patients had the worst graft survival and overall survival (median survival [MS], 30.5 months and 39.7 months, respectively; P < .001), whereas Hispanics had the best survival (MS, 83.4 months and 86.6 months, respectively; P < .001). In a multivariate analysis of transplantation patients, race and ethnicity were associated significantly with outcome.
Significant racial and ethnic disparities in the outcome of patients with HCC persist despite the receipt of comparable treatment. The authors concluded that further investigations are warranted to identify the reasons for the stark disparity in outcomes between black patients and Hispanic patients after liver transplantation for HCC.
Cancer 03/2010; 116(5):1367-77. · 4.77 Impact Factor
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ABSTRACT: 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 disease (CVD). A nested case-controlled 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 1+-year survivors who underwent transplantation at City of Hope between 1977 and 2006. Controls (HCT survivors without CVD) were matched on age, year of HCT, type of HCT, and duration of follow-up. Sixty-three patients with late CVD were identified, 44 (69.8%) with a coronary artery event and 19 (30.2%) with a cerebrovascular event. Median age at HCT was 49.0 years. Median age at onset of late CVD was 54.0 years; 66.7% of the affected patients had undergone autologous HCT. Multivariate logistic regression analysis showed that the presence of multiple cardiovascular risk factors (2 or more of the following: obesity, dyslipidemia, hypertension, and diabetes) after HCT was associated with a 5.2-fold increased risk of late CVD (P < .01), and that pre-HCT chest radiation exposure was associated with a 9.5-fold greater risk of coronary artery disease (P = .03). Pre-HCT exposure to chest radiation and the presence of comorbidities were 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.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(8):1138-44. · 3.15 Impact Factor
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ABSTRACT: 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.
Nutrition and Cancer 01/2010; 62(1):21-9. · 2.78 Impact Factor
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ABSTRACT: BACKGROUND: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 ≥1 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.METHODS:Using a retrospective study design, the authors followed 1346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and disease recurrence. Cox proportional regression techniques were used to identify associated risk factors.RESULTS:The median age at HCT was 34 years (range, 7 months-69 years), and median length of follow-up for those surviving 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 < .001 compared with autologous HCT recipients). For allogeneic transplant recipients, male sex (relative risk [RR], 2.1; 95% confidence interval [95% CI], 1.1-4.0); presence of chronic graft-versus-host disease (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 ≥3 drugs (RR, 9.2; 95% CI, 2.42-35.24).CONCLUSIONS:Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition. Cancer 2009. © 2009 American Cancer Society.
Cancer 09/2009; 115(18):4127 - 4135. · 4.77 Impact Factor
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ABSTRACT: Survival for gastric cancer is reportedly higher in Asians than for other races. It is unclear whether differences in outcome exist among Asian ethnicities. Our objective was to assess gastric cancer survival in Asian ethnic groups in a large heterogeneous population.
Asian-Americans treated for gastric adenocarcinoma between 1988 and 2006 were identified from the Los Angeles County Cancer Surveillance Program. Patients were stratified and compared by ethnicity (Korean, Japanese, Chinese, Vietnamese or Filipino).
Of the 1,817 Asian-Americans in the study cohort, 45% (n = 810) were Korean, 25% (n = 462) were Chinese, 11% (n = 193) were Japanese, 10% (n = 188) were Filipino, and 9% (n = 164) were Vietnamese. For the entire cohort Koreans and Filipinos had the longest and shortest median survival (MS), respectively (22.4 and 10.3 months, respectively; P < 0.001). Multivariate analysis demonstrated that Japanese and Filipino ethnicity independently predicted worse survival compared with Korean ethnicity [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.08-1.73, P = 0.008; and HR 1.71, 95% CI 1.37-2.13, P < 0.001, respectively]. In the surgical cohort, Koreans and Filipinos had the longest and shortest survival, respectively (MS of 57.8 and 21.7 months, respectively; P < 0.001). Multivariate analysis of the surgical cohort also demonstrated that Japanese and Filipino ethnicity independently predicted worse survival compared with Korean ethnicity (HR 1.61, 95% CI 1.22-2.13, P < 0.001; and HR 1.66, 95% CI 1.24-2.22, P < 0.001, respectively).
There are differences in gastric cancer survival among Asian ethnicities. Future studies addressing varying environmental exposures and molecular expression patterns in gastric cancer are warranted to better understand these disparities in outcome.
Annals of Surgical Oncology 08/2009; 16(9):2433-41. · 4.17 Impact Factor
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ABSTRACT: 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 >or=1 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, the authors followed 1346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and disease recurrence. 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 surviving 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<.001 compared with autologous HCT recipients). For allogeneic transplant recipients, male sex (relative risk [RR], 2.1; 95% confidence interval [95% CI], 1.1-4.0); presence of chronic graft-versus-host disease (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 >or=3 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.
Cancer 06/2009; 115(18):4127-35. · 4.77 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Journal of Clinical Oncology 02/2009; 27(5):791-8. · 18.37 Impact Factor
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ABSTRACT: Long-term hematopoietic cell transplantation (HCT) survivors have a high prevalence of severe and chronic health conditions, placing significant demands on the healthcare system. The objective of the current study was to evaluate and compare the healthcare utilization by adult Hispanic and non-Hispanic white long-term survivors of HCT.
A mailed questionnaire was used to assess self-reported healthcare utilization in 3 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 age > or =21 years, and had survived > or =2 years after HCT.
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 a higher proportion of Hispanics reported cancer/HCT center visits at 11+ years after HCT (81% vs 54%).
Compared with non-Hispanic whites, Hispanic survivors are less likely to establish contact with primary care providers years after HCT and to continue to receive care at cancer/HCT centers. Future studies of this population are needed to establish the factors responsible for this pattern of healthcare utilization.
Cancer 10/2008; 113(10):2724-33. · 4.77 Impact Factor
