Association Between Pretreatment Skeletal Muscle and Outcomes After CAR T-Cell Therapy.

BACKGROUND: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. PATIENTS AND METHODS: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. RESULTS: The median age of the cohort was 63.1 years (range, 18.5-82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05-2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P<.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11-2.57) and worse survival (HR, 2.44; 95% CI, 1.49-4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P<.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97-9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81-19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. CONCLUSIONS: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.

Social Vulnerability and Risk of Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Risk of nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT) is high. Patient-level clinical prediction models such as the HCT-comorbidity index (HCT-CI) help identify those at increased risk for NRM, but the independent contribution of social determinants of health on HCT outcomes is not well characterized. METHODS: This study included 1602 patients who underwent allogeneic HCT between 2013 and 2019 at City of Hope. Census tract-level social vulnerability was measured using the social vulnerability index (SVI). Fine-Gray multivariable regression evaluated the association between SVI and 1-year NRM. Subgroup analysis examined risk of NRM across combined SVI and HCT-CI categories and by race and ethnicity. RESULTS: Cumulative incidence of 1-year NRM after HCT was 15.3% (95% confidence interval [CI] = 13.6% to 17.1%). In multivariable analysis, patients in the highest SVI tertile (highest social vulnerability) had a 1.4-fold risk (subdistribution hazard ratio [sHR] = 1.36, 95% CI = 1.04 to 1.78) of NRM compared with individuals in the lower tertiles; patients in the highest SVI tertile who also had elevated (≥3) HCT-CI scores had the highest risk (sHR = 1.81, 95% CI = 1.26 to 2.58) of 1-year NRM (reference: lower SVI tertiles and HCT-CI < 3). High social vulnerability was associated with risk of 1-year NRM in Asian (sHR = 2.03, 95% CI = 1.09 to 3.78) and Hispanic (sHR = 1.63, 95% CI = 1.04 to 2.55) but not non-Hispanic White patients. CONCLUSIONS: High social vulnerability independently associated with 1-year NRM after HCT, specifically among minority populations and those with a high comorbidity burden at HCT. These findings may inform targeted approaches for needs assessment during and after HCT, allowing for timely interventions to improve health outcomes in at-risk patients.

Association Between Body Composition and Development of Glucose Intolerance after Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) recipients have increased risk of developing glucose intolerance and diabetes mellitus (DM). The strongest risk factor for glucose intolerance is being overweight/obese, as determined by body mass index (BMI), which does not account for differences in body composition. We examined the association between body composition measures from pre-HCT CT and early-onset (≤30 days) de novo glucose intolerance after HCT, and determined its impact on nonrelapse mortality (NRM). METHODS: This study included 749 patients without pre-HCT DM. Skeletal muscle loss [abnormal skeletal muscle gauge (SMG)] and abnormal visceral adiposity (VA) were defined by sex-specific tertiles. Fine-Gray proportional subdistribution HR estimates and 95% confidence intervals (CI) were obtained to determine the association between muscle loss and VA and development of glucose intolerance. 1 year NRM was calculated for patients alive at day 30. RESULTS: Median age at HCT was 50.2 years. By day 30, 8.1% of patients developed glucose intolerance and 731 remained alive. In multivariable analysis, abnormal SMG was associated with increased risk of glucose intolerance in nonoverweight (BMI < 25 kg/m2) patients (HR = 3.00; 95% CI, 1.15-7.81; P = 0.024); abnormal VA was associated with increased risk of glucose intolerance in overweight/obese patients (HR = 2.26; 95% CI, 1.24-4.12; P = 0.008). Glucose intolerance was independently associated with NRM (HR = 1.88; 95% CI, 1.05-3.39; P = 0.035). CONCLUSIONS: Abnormal SMG and VA were associated with glucose intolerance in nonoverweight and overweight/obese patients, respectively, which contributed to increased risk of 1 year NRM. IMPACT: This information may guide personalized interventions to decrease the risk of adverse outcomes after HCT. See related commentary by Giri and Williams, p. 2002.

Prevalence and risk factors for vitamin D deficiency in long-term childhood cancer survivors.

BACKGROUND: Childhood cancer survivors (CCS) have increased risk of developing chronic health conditions, including musculoskeletal disorders. Little is known regarding vitamin D deficiency (VDD, <20 ng/ml) and its association with bone mineral density (BMD) in long-term CCS. We evaluated the prevalence and risk factors for VDD in a large, diverse population of long-term CCS, and examined the association between VDD and BMD in patients who underwent guideline-recommended dual-energy X-ray absorptiometry (DXA) screening. METHODS: This cross-sectional study included 446 consecutive CCS seen from March 2018 to September 2020. Univariate analyses examined associations between CCS demographics, socioeconomic status, and treatment exposures and VDD. Multivariable logistic regressions identified factors associated with odds of VDD and reduced BMD. RESULTS: Median age at evaluation was 27.5 years (range 7-67 years); median time from completing therapy was 14.2 years (range 2-65 years). Fifty percent were female, and 45% were Hispanic. Twenty-four percent had VDD. In multivariable analysis, overweight and obese BMI were associated with VDD (overweight: OR 1.78, 95% CI 1.03-3.07, p = 0.04; obese: OR 2.40, 95% CI 1.39-4.13, p < 0.01; reference: normal/underweight), as was Hispanic or black race/ethnicity (OR 2.40, 95% CI 1.41-4.09, p < 0.01; reference: non-Hispanic white). In the 118 CCS with DXA results, VDD was independently associated with reduced BMD (OR 3.58, 95%CI 1.33-9.59, p = 0.01). CONCLUSIONS: CCS have a high prevalence of VDD. High BMI and Hispanic or black race/ethnicity were associated with VDD. Survivors with VDD had a greater than threefold risk of reduced BMD. Risk-based screening may facilitate timely interventions to mitigate VDD and improve BMD in CCS.

Atrial Fibrillation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

PURPOSE: To examine the incidence and risk factors for de novo atrial fibrillation (AF) after allogeneic hematopoietic cell transplantation (HCT) and to describe the impact of AF on HCT-related outcomes. METHODS: A retrospective cohort study design was used to examine AF and associated outcomes in 487 patients who underwent allogeneic HCT from 2014 to 2016 and to characterize patient- and HCT-related risk factors. A nested case-control study design was used to describe the association between pre-HCT echocardiographic measures and future AF events. RESULTS: The median age at HCT was 52.4 years (18.1-78.6); the median time to AF was 117.5 days (4.0-1,405.0). The 5-year cumulative incidence of AF was 10.6%. Older (≥ 50 years) age (hazard ratio [HR], 2.76; 95% CI, 1.37 to 5.58), HLA-unrelated donor (HR, 2.20; 95% CI, 1.18 to 4.12), dyslipidemia (HR, 2.40; 95% CI, 1.23 to 4.68), and pre-HCT prolonged QTc interval (HR, 2.55; 95% CI, 1.38 to 4.72) were independent risk factors for AF. Despite having comparable left ventricular systolic function, patients who developed AF were significantly more likely to have lower left atrial ejection fraction, left atrial reservoir function, and elevated tricuspid regurgitant jet velocity prior to HCT, compared with patients who did not. The incidence rate of stroke after AF was 143 per 1,000 person-years. In adjusted analyses, AF was associated with a 12.8-fold (HR, 12.76; 95% CI, 8.76 to 18.57) risk of all-cause mortality and 15.8-fold (HR, 15.78; 95% CI, 8.70 to 28.62) risk of nonrelapse mortality. CONCLUSION: The burden of AF after allogeneic HCT population is substantial, and the development of AF is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of AF, setting the stage for targeted prevention strategies during and after HCT.

Abnormal body composition is a predictor of adverse outcomes after autologous haematopoietic cell transplantation.

BACKGROUND: The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non-malignant diseases and may predict outcomes after autologous HCT. METHODS: This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non-Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: <43 cm/m2 [body mass index (BMI) < 25 kg/m2 ] or < 53 cm/m2 [BMI ≥ 25 kg/m2 ] and female: <41 cm/m2 [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm2 (male), ≥396.4 cm2 (female)] were assessed from single-slice abdominal pre-HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30-day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan-Meier analysis and Gray's test. RESULTS: Median age at HCT was 53.3 years (range, 18.5 to 78.1 years); 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre-HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.3-9.8], intensive care unit admission (OR = 4.7, 95% CI 1.5-16.1), and unplanned readmission after HCT (OR = 13.6, 95% CI 2.5-62.8). Patients who were sarcopenic obese also had the highest mortality risk at 1 year [hazard ratio (HR): 3.9, 95% CI 1.1-11.0] and 5 years (HR: 2.5, 95% CI 1.1-5.5), compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese. CONCLUSIONS: Sarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT.

Feasibility and Acceptability of Using a Telehealth Platform to Monitor Cardiovascular Risk Factors in Hematopoietic Cell Transplantation Survivors at Risk for Cardiovascular Disease.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in hematopoietic cell transplantation (HCT) survivors. In these patients, such risk factors as hypertension, diabetes, obesity, and physical inactivity are important modifiers of CVD risk. However, the period when HCT survivors are at greatest risk of developing these risk factors, and in turn CVD, coincides with a drop in engagement in survivorship care. We examined the feasibility and acceptability of a 4-week remote risk-based monitoring (blood pressure monitor, weight scale, pulse oximeter, glucometer) and management program in 18 (11 allogeneic and 7 autologous) HCT survivors at intermediate-high risk of CVD. The median patient age was 66 years (range, 53 to 74 years), 67% had hypertension, 22% had diabetes, 11% were obese (body mass index ≥30 kg/m2), 56% were at intermediate risk of CVD, and 44% were at high risk of CVD. Weekly compliance with the remote monitoring schedule (≥3 readings/week using all devices) ranged from 72% in week 1 to 83% in weeks 2 to 4. Fifteen participants (83%) generated 86 alerts that were outside the predetermined range of normal; 63 of these readings (73%) normalized without intervention, and 23 (27%) necessitated triage by the study research nurse. Nearly all participants reported that the study kept them motivated and involved in their healthcare, and >85% agreed that the study supported their healthcare goals, helped them learn and manage their health conditions, and increased their access to healthcare. These findings may set the foundation for innovative risk-based and remote interventions to reduce the burden of CVD in this growing population of patients.

Conditional Survival, Cause-Specific Mortality, and Risk Factors of Late Mortality After Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors' mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantified. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-specific mortality. METHODS: We calculated conditional survival rates and standardized mortality ratio for overall and cause-specific mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976-2014. Statistical tests were two-sided. RESULTS: The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15 years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% confidence interval [CI] = 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95% CI = 3.0 to 4.1). Primary disease accounted for 50% of deaths in the overall cohort and only 10% in 15-year survivors; the leading causes of nondisease-related mortality were subsequent malignancy (26.1%) and cardiopulmonary diseases (20.2%). We also identified the risk factors for nondisease-related mortality in 1- and 5-year survivors. CONCLUSION: Survival probability improves the longer patients survive after HCT. However, HCT recipients surviving 15 years or more remain at elevated mortality risk, largely because of health conditions other than their primary disease. Our study findings help inform preventive and interventional strategies to improve long-term outcomes after allogeneic HCT.

Long-Term Outcomes of Patients with Acute Myelogenous Leukemia Treated with Myeloablative Fractionated Total Body Irradiation TBI-Based Conditioning with a Tacrolimus- and Sirolimus-Based Graft-versus-Host Disease Prophylaxis Regimen: 6-Year Follow-Up from a Single Center.

Cyclophosphamide (Cy)/etoposide combined with fractionated total body irradiation (FTBI) or i.v. busulfan (Bu) has been the main conditioning regimens for allogeneic hematopoietic cell transplantation (alloHCT) for young patients with acute myelogenous leukemia (AML) eligible for a myeloablative conditioning (MAC) regimen. Recent data has suggested that i.v. Bu could be the preferred myeloablative regimen in patients with myeloid malignancies. However, Bu-based regimens are associated with higher rates of sinusoidal obstruction syndrome. Here we report long-term survival outcomes of patients with AML receiving FTBI combined with Cy or etoposide before undergoing alloHCT at City of Hope (COH). We obtained a retrospective review of a prospectively maintained institutional registry of clinical outcomes in 167 patients (median age, 41 years; range, 18 to 57 years) with AML in first or second complete remission who underwent alloHCT at COH between 2005 and 2015. Eligible patients received a MAC regimen with FTBI (1320 cGy) and Cy (120 mg/kg) for unrelated donor transplantation or etoposide (60 mg/kg) for related donor transplantation. Graft-versus-host disease (GVHD) prophylaxis was provided with tacrolimus and sirolimus. In this retrospective study, 6-year overall survival was 60% and nonrelapse mortality was 15%. The GRFS rate was 45% at 1 year and 39% at 2 years. We also describe late metabolic effects and report the cumulative incidence of secondary malignancies (9.5%). Overall, in this young adult patient population, our results compare favorably to chemotherapy-based (i.v. Bu) conditioning regimens without significant long-term toxicity arising from TBI-based regimens.

Association between Clonal Hematopoiesis and Late Nonrelapse Mortality after Autologous Hematopoietic Cell Transplantation.

Clonal hematopoiesis (CH), characterized by the accumulation of acquired somatic mutations in the blood, is associated with an elevated risk of aging-related diseases and premature mortality in non-cancer populations. Patients who undergo autologous hematopoietic cell transplantation (HCT) are also at high risk of premature onset of aging-related conditions. Therefore, we examined the association between pretreatment CH and late-occurring (≥1 year) nonrelapse mortality (NRM) after HCT. We evaluated pathogenic and likely pathogenic CH variants (PVs) in 10 patients who developed NRM after HCT and in 29 HCT recipient controls matched by age at HCT ± 2 years (median, 64.6 years; range, 38.5 to 74.7 years), sex (79.5% male), diagnosis (61.5% with non-Hodgkin lymphoma, 18.0% with Hodgkin lymphoma, and 20.5% with multiple myeloma), and duration of follow-up. We analyzed mobilized hematopoietic stem cell DNA in samples collected before HCT using a custom panel of amplicons covering the coding exons of 79 myeloid-related genes associated with CH. PVs with allele fractions >2% were used for analyses. Cases were significantly more likely than controls to have CH (70% versus 24.1%; P = .002), to have ≥2 unique PVs (60% versus 6.9%; P < .001), and to have PVs with allelic fractions ≥10% (40% versus 3.4%; P = .003). Here we provide preliminary evidence of an association between pre-HCT CH and NRM after HCT independent of chronologic age. Integration of CH analyses may improve the accuracy of existing pre-HCT risk prediction models, setting the stage for personalized risk assessment strategies and targeted treatments to optimally prevent or manage late complications associated with HCT.

Prediction of cardiovascular disease among hematopoietic cell transplantation survivors.

Cardiovascular disease (CVD) is a leading cause of late morbidity and mortality in hematopoietic cell transplantation (HCT) survivors. HCT-specific CVD risk prediction models are needed to facilitate early screening and prevention. In the current study, patients who underwent HCT at City of Hope (COH) and survived 1-year free of clinically evident CVD (N = 1828) were observed for the development of heart failure (HF) or coronary artery disease (CAD) by 10-years from index date (1 year from HCT). CVD occurred in 135 individuals (92 HF, 43 CAD). Risk prediction models were developed for overall CVD (HF and/or CAD) using COH-derived integer risk scores. Risk scores based on selected variables (age, anthracycline dose, chest radiation, hypertension, diabetes, smoking) achieved an area under the curve (AUC) and concordance (C) statistic of 0.74 and 0.72 for CVD; these varied from 0.70 to 0.82 according to CVD subtype (HF or CAD). A Fred Hutchinson Cancer Research Center case cohort (N = 580) was used to validate the COH models. Validation cohort AUCs ranged from 0.66 to 0.75. Risk scores were collapsed to form statistically distinct low-, intermediate-, and high-risk groups, corresponding to 10-year cumulative incidences of CVD of 3.7%, 9.9%, and 26.2%, respectively. Individuals in the high- and intermediate-risk groups were at 7.8-fold (95% confidence interval, 5.0-12.2) and 2.9-fold (95% confidence interval, 1.9-4.6) risk of developing CVD (referent group: low risk). These validated models provide a framework on which to modify current screening recommendations and for the development of targeted interventions to reduce the risk of CVD after HCT.

Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients: Results From the Bone Marrow Transplant Survivor Study.

IMPORTANCE: Frailty results in decreased physiological reserve and diminished resistance to stressors; approximately 10% of those in the elderly population (those ≥65 years) are frail. High-intensity treatments and complications after hematopoietic cell transplantation (HCT) injure normal tissues and may increase the risk of frailty even among nongeriatric HCT patients. OBJECTIVE: To determine the prevalence of frailty in young adult HCT patients (18- to 64-year-olds) and siblings; and the impact of frailty on subsequent mortality in HCT survivors. DESIGN, SETTING, AND PARTICIPANTS: This cohort study, conducted in August 2015 examined 998 HCT survivors, who underwent transplant procedures between 1974 and 1998, who have survived at least 2 years after HCT, and 297 frequency-matched siblings. The study was performed at City of Hope or University of Minnesota with participants completing surveys at home or in the clinic. Hematopoietic cell transplantation survivors and siblings participating in the Bone Marrow Transplant Survivor Study (BMTSS) completed a frailty survey between February 13, 1999 and June 15, 2005 (median time since HCT: 7.9 years); HCT survivors were followed for subsequent mortality (median: 10.3 years from survey). MAIN OUTCOMES AND MEASURES: Prevalence and predictors of frailty; impact of frailty on subsequent mortality in HCT survivors. Frailty phenotype defined as exhibiting 3 or more of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The national Death Index, Social Security Death Index and medical records were used for mortality assessment as of December 21, 2011. RESULTS: The 998 HCT survivors were a mean (SD) of 42.5 (11.6) years of age, and the 297 matched siblings were 43.8 (10.9) years of age. The prevalence of frailty among young adult HCT patients exceeded 8%. The HCT survivors were 8.4 times more likely to be frail than their siblings (95% CI, 2.0-34.5; P = .003). Among HCT recipients, allogeneic HCT recipients with chronic graft-vs-host disease (GvHD) were at increased risk of frailty compared with autologous HCT (OR,15.02; 95% CI, 6.6-34.3; P < .001); resolved chronic GvHD (OR, 2.7; 95% CI, 1.1-6.9; P = .04). Cumulative incidence of subsequent all-cause mortality was 39.3% and 14.7% at 10 years for HCT recipients with and without frailty, respectively (P < .001). Frailty was associated with a 2.76-fold (95% CI, 1.7-4.4; P < .001) increased risk of subsequent mortality after adjusting for relevant prognosticators. CONCLUSIONS AND RELEVANCE: The prevalence of frailty among young-adult HCT survivors approaches that seen in the elderly general population. Frail HCT survivors are at increased risk of subsequent mortality when compared with nonfrail survivors. This study identifies vulnerable populations needing close monitoring to anticipate and manage morbidity and prevent mortality.

Second primary malignancies after autologous hematopoietic cell transplantation for multiple myeloma.

Recent studies demonstrate an increased risk of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving maintenance lenalidomide after autologous stem cell transplantation (ASCT). We explored the possibility of other risk factors driving post-ASCT SPMs in patients with MM through analysis of our large transplantation database in conjunction with our Long-Term Follow-Up Program. We conducted a retrospective cohort study of 841 consecutive patients with MM who underwent ASCT at City of Hope between 1989 and 2009, as well as a nested case-control analysis evaluating the role of all therapeutic exposures before, during, and after ASCT. Median duration of follow-up for the entire cohort was 3.4 years (range, 0.3-19.9 years). Sixty cases with a total of 70 SPMs were identified. The overall cumulative incidence of SPMs was 7.4% at 5 years and 15.9% at 10 years when nonmelanoma skin cancers (NMSCs) were included and 5.3% at 5 years and 11.2% at 10 years when NMSCs were excluded. Multivariate analysis of the entire cohort revealed associations of both older age (≥55 years; relative risk, 2.3; P < .004) and race (non-Hispanic white; relative risk, 2.4; P = .01) with an increased risk of SPM. Furthermore, thalidomide exposure demonstrated a trend toward increased risk (odds ratio, 3.5; P = .15); however, an insufficient number of patients were treated with lenalidomide to allow us to accurately assess the risk of this agent. Exclusion of NMSCs retained the association with these variables but was accompanied by loss of statistical significance. This large single-institution analysis identified associations between race and older age and increased risk of developing SPM. The trend toward increased risk with thalidomide exposure suggests a class effect from immunomodulatory drugs that might not be restricted to lenalidomide.

Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS).

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.

Ethnic differences in chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Predictors of late cardiovascular complications in survivors of hematopoietic cell transplantation.

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.