Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. However, long-term survival is challenged by late relapse, late complications and late ...non-relapse mortality, and HCT survivors need continued lifelong surveillance for screening, early detection and timely treatment of late complications such as secondary cancers, late infections and organ toxicity. Guidelines for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT were updated and published in 2012. However, several barriers to the care of HCT survivors and routine utilization of these guidelines in clinical practice exist. Examples include paucity of and challenges to conducting prospective randomized trials for screening and prevention of late complications, lack of resources to manage late effects at the level of transplant centers and community health care providers, and inadequate tools to facilitate care and followup of HCT survivors. We summarize the long-term followup guidelines in this review, discuss ways that providers can integrate and utilize them for the care of their patients, and identify areas for research that can inform and increase the utilization of screening and prevention guidelines in clinical practice.
There is a lack of multi-center cost-identification studies for hematopoietic cell transplantation (HCT). We used a single longitudinal administrative claims database representing a national, ...commercially insured population to evaluate the feasibility of identifying HCT recipients and to establish a cohort of autologous and allogeneic HCT recipients to study inpatient and outpatient direct medical costs from transplant hospitalization through first 100 days post-transplantation. Using ICD-9 procedure and diagnosis codes, we identified 3365 patients who had received their first transplant in the United States between 2007 and 2009 (autologous, 1678, allogeneic, 1320, graft source not specified, 367). The median 100-day total costs for autologous HCT were $99,899 (interquartile range (IQR), $73,914-140,555), and for allogeneic HCT were $203,026 (IQR, $141,742-316 ,426). The majority of costs (>75%) occurred during the initial transplant hospitalization for both autologous and allogeneic HCT recipients. Costs were greater among pediatric (< or =20 years) compared with adult (>20 years) recipients and this difference was more pronounced with allogeneic HCT. Using a claims database representing a national HCT population, we highlight the high costs associated with autologous and allogeneic HCT. Our study lays the foundation for using claims data for future research on economic aspects of HCT.
Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, ...introduction of newer graft sources (for example, umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri- and post-transplant exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplant experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This report provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.
Hematopoietic cell transplantation (HCT) is a highly specialized, expensive and resource-intense medical procedure that can be associated with racial disparities. We review the prevailing literature ...on racial disparities in HCT in the United States and describe areas for future research and interventions. We discuss the complexity of interpreting race as a biological and social determinant of disease in biomedical research, especially as it relates to HCT. In the United States, race is often a surrogate for socioeconomic, education and health insurance status. We also discuss some of the nuances to consider while reviewing the literature on racial disparities. Disparities by race exist in three areas related to HCT: donor availability, access to HCT and outcomes of HCT. African-Americans/Blacks have a lower likelihood of finding an unrelated donor. Race and ethnicity definitions are country-specific and reconciling race data can represent significant challenges to unrelated donor registries worldwide. African-Americans/Blacks do not have the same access to autologous and allogeneic HCT as Whites. Racial disparities in outcomes of HCT are more prevalent among allogeneic HCT than autologous HCT recipients. More research is required to understand the biological, social, cultural, medical and financial aspects of race that may influence access to HCT and survival after transplantation. Better understanding of racial disparities will minimize inequities, inform health policy, guide development of interventions targeted to eliminate disparities and ensure equitable access to HCT for all populations.
We conducted a cross-sectional study to estimate the prevalence of metabolic syndrome, a clustering of risk factors associated with cardiovascular disease, among 86 adults who had allogeneic ...hematopoietic-cell transplant (HCT) as compared with 258 age- and gender-matched US population controls selected from the 2005-2006 National Health and Nutrition Examination Survey database. The median age at study enrollment was 50 years (range, 21-71), and patients were at a median of 3 years (range, 1-21) from HCT. The prevalence of metabolic syndrome was 49% (95% confidence intervals (CI), 38-60%) among HCT recipients, a 2.2-fold (95% CI, 1.3-3.6, P=0.002) increase compared with controls. The prevalence rates of elevated blood pressure and hypertriglyceridemia were significantly higher among HCT recipients than among controls, but the prevalence rates of abdominal obesity, elevated blood glucose and low high-density lipoprotein cholesterol were not. HCT survivors with metabolic syndrome were more likely to have microalbuminuria (43 vs 10%) and elevated creatinine (31 vs 11%). No patient, donor or transplant characteristics were associated with the diagnosis of metabolic syndrome. We conclude that metabolic syndrome occurs frequently among allogeneic HCT survivors who are seen by transplant physicians. Approaches to screening, prevention and management of metabolic syndrome should be developed for HCT recipients.
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A ...working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility ...is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT 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.
Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic cell transplant (HCT) recipients. Iron overload increases the risk of infections, ...veno-occlusive disease and hepatic dysfunction post transplant. Elevated pretransplant ferritin levels have been reported to increase the risk of nonrelapse mortality following HCT and might influence the risk of acute and chronic GVHD. Serum ferritin is sensitive but not specific for iron overload and is a poor predictor of body iron burden. Estimation of hepatic iron content with a liver biopsy or magnetic resonance imaging should be considered prior to initiating therapy for post transplant iron overload. A subgroup of transplant survivors with mild iron overload and no end-organ damage may not need therapy. Phlebotomy is the treatment of choice with iron-chelation therapy reserved for patients not eligible for phlebotomy. Natural history, evolution and treatment of iron overload in transplant survivors have not been adequately investigated and more studies are needed to determine its impact on short-term and long-term morbidity and mortality.
Patient/caregiver out-of pocket costs associated with hematopoietic cell transplantation (HCT) are not well known. We conducted a pilot study to evaluate patient/caregiver out-of-pocket costs in the ...first 3 months after allogeneic HCT. Thirty patients were enrolled at three sites. Before HCT, participants completed a baseline survey regarding household income and insurance coverage. Subsequently, they maintained a paper-based diary to track daily out-of-pocket expenses for the first 3 months after HCT. Telephone interviews were conducted to follow-up on the missing/incomplete diaries and on study completion. Twenty-five patients/caregivers completed the baseline survey. Among these, the median pre-tax household income was $66 500 (range, $30-$375 000) and 48% had to temporarily relocate close to the transplant center. Insurance coverage was managed care plan (56%), Medicaid (20%), Medicare (17%) and other (8%). Twenty-two patients/caregivers completed 4 diaries; the median out-of-pocket expenses were $2440 (range, $199-$13 769). Patients/caregivers who required temporary lodging had higher out-of-pocket expenses compared with those who did not (median, $5247 vs $716). Patients/caregivers can incur substantial out-of-pocket costs over the first 3 months, especially if they need to temporarily relocate close to the transplant center. Our study lays the foundation for future research on the early and long-term financial impact of allogeneic HCT on patients/caregivers.
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