Late effects in survivors of chronic myeloid leukemia treated with hematopoietic cell transplantation: results from the Bone Marrow Transplant Survivor Study. Baker K Scott,Gurney James G,Ness Kirsten K,Bhatia Ravi,Forman Stephen J,Francisco Liton,McGlave Philip B,Robison Leslie L,Snyder David S,Weisdorf Daniel J,Bhatia Smita Blood The purpose of this study was to analyze medical late effects among patients with chronic myeloid leukemia (CML) treated with hematopoietic cell transplantation (HCT). Subjects included 248 CML survivors who received an HC transplant (related donors [RDs], n = 150; unrelated donors [URDs], n = 70; or autologous, n = 28) and had survived at least 2 years, and a comparison group of 317 siblings. Subjects completed a 238-item survey on medical late effects. Compared with siblings, survivors were at a higher risk of developing ocular, oral health, endocrine, gastrointestinal, musculoskeletal, neurosensory, and neuromotor impairments. Multivariate analysis limited to RD and URD recipients found that chronic graft-versus-host disease (cGVHD) was associated with a higher risk of hypothyroidism, osteoporosis, cardiopulmonary, neurosensory, and neuromotor impairments. Overall health was reported as excellent, very good, or good in 78% of subjects, although those with cGVHD were more likely to report poor overall health. URD survivors were more likely to report a need for assistance with routine activities and that their current health prevented work or school attendance. This study demonstrates that HCT survivors, regardless of donor type, have a high prevalence of long-term health-related complications. However, adverse medical late effects with significant morbidity were uncommon. Chronic GVHD is the most important predictor of adverse medical late effects and poor overall health. 10.1182/blood-2004-03-1010
    Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease. Pirsl Filip,Curtis Lauren M,Steinberg Seth M,Tella Sri Harsha,Katić Mašenjka,Dobbin Marnie,Hsu Jennifer,Hakim Fran T,Mays Jacqueline W,Im Annie P,Pulanić Dražen,Mitchell Sandra A,Baruffaldi Judy,Masuch Licia,Halverson David C,Gress Ronald E,Barsony Julianna,Pavletic Steven Z Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation The National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients, and the guidelines are based on experience with other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD because of prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score ≤-2.5) at 3 anatomic sites-the femoral neck (FN), lumbar spine (LS), and total hip (TH)-and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN, P < .0001; LS, P = .0002; TH, P < .0001), malnutrition (FN, P = .0002; LS, P = .03; TH, P = .0076), higher platelet count (FN, P = .0065; TH, P = .0025), higher average National Institutes of Health organ score (FN, P = .038), higher prednisone dose (LS, P = .032), lower complement component 3 (LS, P = .0073), and physical inactivity (FN, P = .01) were associated with osteoporosis in at least 1 site. T-scores were significantly lower in the FN compared with the LS or TH (P < .0001 for both). The prevalence of osteoporosis and osteopenia was high (17% and 60%, respectively), supporting current recommendations for frequent monitoring of BMD. The association of higher platelet count in patients with cGVHD and osteoporosis has not been reported previously and represents a new area of interest in the study of osteoporosis after allogeneic hematopoietic stem cell transplantation. 10.1016/j.bbmt.2016.04.012
    Guidance to Bone Morbidity in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Kuhlen Michaela,Kunstreich Marina,Niinimäki Riitta,Dunstheimer Desiree,Lawitschka Anita,Bardi Edit,Willasch André,Bader Peter,Högler Wolfgang,Peters Christina,Balduzzi Adriana Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Allogeneic hematopoietic stem cell transplantation (HSCT) is widely performed in children and adolescents with hematologic diseases, including very high-risk leukemia. With increasing success and survival rates, the long-term sequelae of HSCT have become important. Here, we provide guidance to the prevention and treatment of the most common bone morbidities-osteoporosis and osteonecrosis-emerging in the context of HSCT in children and adolescents. We give an overview on definitions, symptoms, and diagnostics and propose an algorithm for clinical practice based on discussions within the International Berlin Frankfurt Münster (BFM) Stem Cell Transplantation Committee and the Pediatric Disease Working Party of the European Society for Blood and Marrow Transplantation, our expert knowledge, and a literature review. 10.1016/j.bbmt.2019.10.007
    Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients. McClune B L,Polgreen L E,Burmeister L A,Blaes A H,Mulrooney D A,Burns L J,Majhail N S Bone marrow transplantation 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. 10.1038/bmt.2010.198
    [Management of endocrine dysfunctions after allogeneic hematopoietic stem cell transplantation: a report of the SFGM-TC on adrenal insufficiency and osteoporosis]. Cornillon J,Vantyghem M-C,Couturier M A,de Berranger E,François S,Hermete E,Maillard N,Marcais A,Tabrizi R,Decanter C,Duléry R,Bauters F,Yakoub-Agha I, Pathologie-biologie In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview on secondary adrenal insufficiency and osteoporosis post-transplant. 10.1016/j.patbio.2013.07.009
    Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors. Anandi P,Jain N A,Tian X,Wu C O,Pophali P A,Koklanaris E,Ito S,Savani B N,Barrett J,Battiwalla M Bone marrow transplantation Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3-22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery. 10.1038/bmt.2016.85