Anne H. Blaes

Shared Risk Factors in Cardiovascular Disease and Cancer

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them.

Estimated number of prevalent cases of metastatic bone disease in the US adult population.

Background The prevalence of metastatic bone disease in the US population is not well understood. We sought to estimate the current number of US adults with metastatic bone disease using two large administrative data sets. Methods Prevalence was estimated from a commercially insured cohort (ages 18–64 years, MarketScan database) and from a fee-for-service Medicare cohort (ages ≥65 years, Medicare 5% database) with coverage on December 31, 2008, representing approximately two-thirds of the US population in each age group. We searched for claims-based evidence of metastatic bone disease from January 1, 2004, using a combination of relevant diagnosis and treatment codes. The number of cases in the US adult population was extrapolated from age- and sex-specific prevalence estimated in these cohorts. Results are presented for all cancers combined and separately for primary breast, prostate, and lung cancer. Results In the commercially insured cohort (mean age = 42.3 years [SD = 13.1]), we identified 9505 patients (0.052%) with metastatic bone disease. Breast cancer was the most common primary tumor type (n = 4041). In the Medicare cohort (mean age = 75.6 years [SD = 7.8]), we identified 6427 (0.495%) patients with metastatic bone disease. Breast (n = 1798) and prostate (n = 1862) cancers were the most common primary tumor types. We estimate that 279,679 (95% confidence interval: 274,579–284,780) US adults alive on December 31, 2008, had evidence of metastatic bone disease in the previous 5 years. Breast, prostate, and lung cancers accounted for 68% of these cases. Conclusion Our findings suggest that approximately 280,000 US adults were living with metastatic bone disease on December 31, 2008. This likely underestimates the true frequency; not all cases of metastatic bone disease are diagnosed, and some diagnosed cases might lack documentation in claims data.

Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients

Long-term survivors of hematopoietic cell transplantation (HCT) are at risk for loss of bone mineral density (BMD) and subsequent osteoporosis. There is a lack of clear guidelines for the screening, prevention and treatment of bone loss after HCT. We reviewed the prevailing literature and provide guidelines developed by our center for the screening and management of this complication. Bone loss occurs predominantly within the first 6–12 months after autologous and allogeneic HCT. Recovery first occurs in the lumbar spine and is followed by a slower recovery of BMD in the femoral neck. BMD may not return to baseline levels in patients with continuing exposure to corticosteroids and calcineurin inhibitors. All HCT recipients should be advised general interventions to reduce fracture risk including adequate intake of calcium and vitamin D. We recommend screening all adult allogeneic and autologous HCT recipients with dual-energy X-ray absorptiometry 1 year after transplantation. Patients at high risk for bone loss (for example, patients receiving ⩾5 mg of prednisone equivalent daily for >3 months) can be screened earlier (for example, 3–6 months after HCT). Where indicated, bisphosphonates or other anti-resorptive agents (for example, calcitonin) can be used for prevention or treatment of osteoporosis in adult HCT recipients. Pediatric HCT recipients should be referred to a pediatric endocrinologist for evaluation and treatment of bone loss. There remain several areas of uncertainty that need further research in adult and pediatric HCT recipients, such as the optimal timing and frequency of screening for loss of bone mineral density, relationship of bone loss with risk of fractures, selection of appropriate patients for pharmacologic therapy, and optimal dosing schedule and duration of therapy with anti-resorptive agents.

Monitoring and preemptive rituximab therapy for Epstein-Barr virus reactivation after antithymocyte globulin containing nonmyeloablative conditioning for umbilical cord blood transplantation.

Epstein Barr viremia (EBV) and posttransplantation lymphoproliferative disorder (PTLD) are complications of hematopoietic stem cell transplantation (HSCT). The use of antithymocyte globulin (ATG) in recipients of umbilical cord HSCT is a known risk factor for the development of PTLD. In this high-risk population, we implemented an EBV monitoring program with preemptive therapy with rituximab (375 mg/m(2) intravenously [i.v.]) for EBV viremia (>1000 copies/mL). Eight of 35 patients treated with a UCB HSCT between 2007 and 2009, developed EBV viremia. Two of 7 developed PTLD (with 1 of the 2 dying of PTLD), despite prophylactic rituximab use. When compared with our previously described cohort where 6 of 30 developed EBV viremia and 5 of 6 patients developed PTLD (with 2 of 5 dying of PTLD), the incidence of PTLD appears to be less when prophylactic rituximab is administered. Despite small numbers, our observations suggest that in this high-risk population, EBV monitoring accompanied by preemptive therapy may reduce the risk of progression to life-threatening PTLD; further follow-up of this cohort and a larger multi-institutional prospective study of this preemptive strategy is warranted.

Patient Satisfaction with Physician Discussions of Treatment Impact on Fertility, Menopause and Sexual Health among Pre-menopausal Women with Cancer

PURPOSE: Pre-menopausal women with cancer are at risk of therapy-associated infertility, premature menopause, and sexual dysfunction. However, it is unknown whether oncologists adequately address these risks during treatment planning. We conducted a study to evaluate physician-patient discussions addressing the impact of cancer treatment and actual treatment effects on fertility, menopause status, and general sexual health. METHODS: A questionnaire was administered in four oncology clinics specializing in breast, gynecologic, general hematology-oncology, and blood and marrow transplantation (BMT) cancer care at a single institution. Eligible participants were pre-menopausal at the time of diagnosis and either actively receiving or within 24 months from completion of treatment. Participants completed the questionnaire at enrollment and at 1-year follow-up. RESULTS: Of the 104 eligible women, a majority were satisfied with the quality (68%) and length (66%) of reproductive health discussions, with the highest satisfaction levels in the gynecologic cancer clinic (85%) and the lowest levels in the BMT clinic (53%). Fertility preservation was desired by 20% of women, including some >40 years old. Women were more interested in discussing treatment impact on menopause status and sexual health than fertility. Rates of discussions on treatment impact on sexual health were low despite 77% of women reporting severe sexual dysfunction at 1-year follow-up. CONCLUSIONS: One-third of women are dissatisfied with the quality and length of discussions regarding the impact of cancer treatment on reproductive health. There is notably inadequate counseling on the effect of treatment on fertility in women > 40 and on sexual function in all women. Oncologists must offer better resources and improve communication on the effect of treatment on reproductive health to pre-menopausal women with cancer.

Corticosteroid Dose as a Risk Factor for Avascular Necrosis of the Bone after Hematopoietic Cell Transplantation

Exposure to corticosteroids increases the risks of avascular necrosis (AVN) of the bone after hematopoietic cell transplantation (HCT). However, whether this effect is dependent on the dose of corticosteroids is not well known. We conducted a case-controlled study, which included 74 recipients of autologous or allogeneic HCT with AVN and 147 controls without AVN that were matched by age, sex, and year of HCT to cases. Cases with AVN included 8 autologous HCT recipients, 58 myeloablative allogeneic HCT recipients, and 8 recipients of non-myeloablative allogeneic HCT. Corticosteroid exposure was expressed as cumulative doses of prednisone. Cases received higher cumulative doses of prednisone than controls, and among allogeneic HCT recipients, cases were more likely to have developed acute and chronic graft-versus-host disease (aGVHD, cGVHD). Cumulative dose of prednisone was an independent risk factor for AVN. Compared to no corticosteroid exposure, exposure to <3870 mg cumulative dose of prednisone was associated with 4.0 (95% confidence intervals, 1.5-11.2) times higher risk, 3870-9735 mg with 5.6 (2.1-15.2) times higher risk and >9735 with 8.6 (3.2-23.5) times higher risk of AVN. Exposure to higher doses of corticosteroids increases the risk of AVN in HCT recipients.

Positron emission tomography scanning in the setting of post‐transplant lymphoproliferative disorders

Abstract:  Background:  Post‐transplant lymphoproliferative disorder (PTLD) is a serious complication of transplantation. We examined the role of positron emission tomography (PET) scanning in PTLD.

Post-transplant lymphoproliferative disorders in lung transplant recipients: 20-yr experience at the University of Minnesota.

Wudhikarn K, Holman CJ, Linan M, Blaes AH, Dunitz JM, Hertz ME, Peterson BA. Post‐transplant lymphoproliferative disorders in lung transplant recipients: 20‐yr experience at the University of Minnesota.
Clin Transplant 2011: 25: 705–713.

Post-transplant lymphoproliferative disorders following solid-organ transplantation

A post-transplant lymphoproliferative disorder (PTLD) is an uncommon but serious complication following solid-organ transplantation. The incidence varies, depending on the type of organ transplanted, the degree of immunosuppression, the number of episodes of acute rejection and a patient’s immune status to Epstein–Barr virus. The incidence of PTLD is thought to be bimodal; cases in the first year after solid-organ transplantation are typically related to Epstein–Barr virus. A second incidence occurs more than 1 year following transplantation and is typically not related to Epstein–Barr virus. A variety of therapeutic approaches has been used for these patients, with more recent strategies including the use of rituximab, with or without combination chemotherapy. Efforts continue to be made to improve the outcome of patients with PTLD.

Breast and colorectal cancer survivors’ knowledge about their diagnosis and treatment

IntroductionAspects of a personal cancer history can have implications for future decisions regarding screening, diagnosis, and treatment. Clinicians must sometimes rely on patients’ self-report of their medical history. This study assessed knowledge of details of cancer diagnosis and treatment among breast and colorectal cancer survivors.MethodsWritten surveys were completed by 480 breast cancer survivors and 366 colorectal cancer survivors diagnosed between 1999 and 2008 at a large cancer center in the Minneapolis, MN, area (81% response rate). Responses were compared with cancer registry and medical records.ResultsForty percent of breast cancer survivors and 65% of colorectal cancer survivors were unable to identify their stage of disease. Seven percent of breast cancer survivors and 21% of colorectal cancer survivors in whom regional nodes were examined did not know whether they had positive nodes. Accuracy of knowledge of estrogen and progesterone status among breast cancer survivors was 58% and 39%, respectively. Of breast cancer survivors treated with doxorubicin, 43% correctly identified it as a drug they had received. Their accuracy of identification of receipt of tamoxifen or specific aromatase inhibitors was >90%. Of colorectal cancer survivors treated with oxaliplatin, 52% correctly identified it as a drug they had received. Accuracy on many items decreased with patient age.ConclusionsThis study identifies several gaps in adult cancer survivors’ knowledge of details of their diagnosis and treatment that have implications for follow-up care.Implications for cancer survivorsProvision of written treatment summaries to cancer survivors could help them obtain appropriate patient-centered long-term follow-up care.