• We identified distinct groups of HCT survivors at low, intermediate, and high risk of developing late-occurring CVD.• The prediction model had good discrimination across outcomes and was validated in an external cohort of HCT survivors. 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.

• Before HCT 61% of men and 37% of women were sexually active; the 3-year prevalence declined to 54% for men but increased to 52% for women.• Chronic GVHD in both sexes and TBI in men contribute to sexual dysfunction and dissatisfaction over the 3 years following HCT.This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P 5 .01) in men and increased to 48% (P 5 .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P £ .001). Orgasm (P 5 .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P 5 .01) and sexual behavior/ experience (P 5 .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P 5 .003) and orgasm (P 5 .006) in men and sexual arousal (P 5 .05) and sexual satisfaction (P 5 .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being. (Blood. 2013;122(24):3973-3981)

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.

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 &lt; 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.

Background: t-MDS/AML is the leading cause of non-relapse mortality after aHCT for NHL. Older age at aHCT, exposure to total body irradiation (TBI), and low number of CD34+ cells infused are associated with an increased risk of developing t-MDS/AML. However, over the past decade, aHCT has been increasingly used for older patient populations (potential for increase in t-MDS/AML risk). On the other hand, use of TBI has declined and number of CD34+ cells infused has increased (potential for decrease in t-MDS/AML risk). The impact of these changes in aHCT clinical practice on t-MDS/AML risk has not been assessed, and is addressed here. Methods: Information regarding t-MDS/AML diagnosis was procured from medical records and California Cancer Registry to ensure near-complete capture of events. Competing risk analysis was used to describe the cumulative incidence of t-MDS/AML, and to evaluate the role of host and aHCT-related factors in the development of t-MDS/AML. In order to understand the impact of changing clinical practices, patients were classified into those transplanted in the early era (1986-2002) vs. recent era (2003-2009). Results: A total of 1,261 consecutive patients received aHCT for NHL between 1986 and 2009 at City of Hope, and were followed for development of t-MDS/AML until 12/31/2011. Median age at aHCT was 50y (range, 5-78). Compared with patients transplanted in early era, those transplanted in recent era were more likely to be ≥50y at aHCT (recent era: 65% vs early era: 44%, p<0.001); less likely to be conditioned with TBI (recent era: 17% vs. early era: 67%, p<0.001); but more likely to receive a larger CD34+ cell dose (>3x10(6)/Kg: recent era 18% vs. early era: 12%, p<0.0001). After a median follow-up of 4.8y (range, 0.02-24.6),78 patients developed t-MDS/AML, yielding a 15y cumulative incidence of 7.5%. The cumulative incidence of t-MDS/AML was higher among those ≥50y (10.0% vs. 5.3%, p=0.002), and among those exposed to TBI (8.8% vs. 5.2%, p=0.07). Taken together, older patients exposed to TBI had a significantly higher cumulative incidence of t-MDS/AML (10.9%), as compared with younger patients not exposed to TBI (2.3%, p<0.001, Figure). Furthermore, the cumulative incidence of t-MDS/AML was higher among those with a low CD34+ cell dose (<3x10(6)/Kg) (14.2%) vs. those with a high CD34+ cell dose (≥3x10(6)/Kg) infusion (4.3%, p<0.0001). Multivariable competing risk analysis (adjusted for era) demonstrated the independent and significant impact of older age (≥50y: HR=2.4, 95%CI, 1.5-3.9, p=0.0004 [ref grp: <50y]), exposure to TBI (HR=1.8, 95%CI, 1.1-3.1, p=0.02 [ref grp: no TBI]), and low CD34+ cell count (<3x10(6)/Kg, HR=3.3, 95%CI, 1.9-5.8, p<0.0001 [ref grp: ≥3x10(6)/Kg]) in increasing the risk of t-MDS/AML. The impact these findings in light of changing practices with time is detailed in Table and summarized here. Multivariable analysis (taking age at aHCT into account) demonstrated that the risk of t-MDS/AML was reduced by 50% among those transplanted in the recent era (HR=0.5, 95%CI, 0.3-0.9, p=0.03 [ref grp: early era]) (Model 1). However, inclusion of TBI and CD34+ cell count in the model abrogated the reduction in the risk of t-MDS/AML during the recent era (HR=0.97, 95%CI, 0.5-1.9, p=0.9, referent grp: early era) (Model 2). Conclusions: This large study spanning over 25y confirms the independent role of age at aHCT, TBI, and CD34+ cell count in t-MDS/AML risk. More importantly, the study delineates the risk of t-MDS/AML in the context of changes in clinical practice of aHCT for NHL, demonstrating a reduction in the incidence of t-MDS/AML (despite an increase in age limit for aHCT) that is likely due to the declining practice of using TBI and the ability to use a higher number of CD34+ cells for aHCT. Table Model 1 Model 2 Model 3 HR (95% CI), p-value HR (95% CI), p-value HR (95% CI), p-value Era of aHCT 1986-2002 1.0 1.0 1.0 2003-2009 0.54 (0.3-0.9), p=0.03 0.71 (0.4-1.3), p=0.3 0.97 (0.5-1.9) p=0.9 Age at aHCT <50y 1.0 1.0 1.0 ≥50y 2.09 (1.3-3.4), p=0.002 2.25 (1.4-3.6), p=0.0007 2.41 (1.5-3.9) p=0.0004 Conditioning with TBI No TBI 1.0 1.0 Yes TBI 1.80 (1.1-3.0), p=0.02 1.8 (1.1-3.1) p=0.02 CD 34 counts >3 1.0 ≤3 3.32 (1.9-5.8) p<0.001 missing 2.36 (1.2-4.5) p=0.01 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.