Xerxes Pundole

Increased Incidence of Fractures in Recipients of Hematopoietic Stem-Cell Transplantation

PURPOSE The number of long-term survivors after hematopoietic stem-cell transplantation (HSCT) for malignant and nonmalignant disorders is increasing, and late effects are gaining importance. Osteoporosis and fractures can worsen the quality of life of HSCT survivors, but the burden of the disease is unknown. PATIENTS AND METHODS We conducted a retrospective study of patients older than age 18 years who underwent an HSCT at The University of Texas MD Anderson Cancer Center from January 1, 1997, to December 31, 2011, and were observed until December 31, 2013, to ascertain occurrence of fractures. Cumulative incidence rates of fractures were calculated with death as a competing risk. Age- and sex-specific incidence rates per person-year of fracture were compared with those of the US general population by using estimated rates from the 1994 National Health Interview Survey and the 2004 National Hospital Discharge Survey. RESULTS A total of 7,620 patients underwent an HSCT from 1997 to 2011 at the MD Anderson Cancer Center of whom 602 (8%) developed a fracture. Age, underlying disease, and HSCT type were significantly associated with fracture. Age- and sex-specific fracture incidence rates after HSCT were significantly greater than those of the US general population in almost all subgroups. The striking difference was an approximately eight times greater risk in females and approximately seven to nine times greater risk in males age 45 to 64 years old when compared with the National Health Interview Survey and National Hospital Discharge Survey fracture rates. CONCLUSION The incidence of fractures is compellingly higher after HSCT.

Prevention and treatment of bone loss and fractures in patients undergoing a hematopoietic stem cell transplant: A systematic review and meta-analysis

The most effective method to prevent and treat bone loss following hematopoietic stem cell transplantation (HSCT) remains uncertain. We conducted a comprehensive search in four electronic databases until August 2015. We retrieved articles describing patients with bone loss or fractures who received HSCT. Controlled trials, with a follow-up period of at least 12 months, were included. Twelve studies (19 publications) met our inclusion criteria. A total of 643 participants underwent HSCT (85.7% allogeneic HSCT). There was a statistically significant lower mean bone mineral density (g/cm2) percentage change of the lumbar spine (mean difference (MD) 7.8, 95% confidence interval (CI) 5.6–10.0) and femoral neck (MD 6.7, 95% CI 5.6–7.9) in the bisphosphonate therapy group compared with the control group with no bisphosphonate therapy at 12 months. In a subgroup analysis, seven different comparison groups were evaluated. The rate of fractures or X-ray findings of subclinical vertebral fractures was similar between groups. Bisphosphonates are promising in the prevention and treatment of bone loss following HSCT. Additional research is required to determine whether they reduce long-term fracture risk.

Ibandronate for the prevention of bone loss after allogeneic stem cell transplantation for hematologic malignancies: a randomized-controlled trial

The purpose of this study was to evaluate the effects of ibandronate on bone loss following allogeneic stem cell transplantation (allo-SCT). A single-centered, open-label prospective randomized-controlled study following allo-SCT. The treatment group received 3 mg of intravenous ibandronate quarterly starting within 45 days of allo-SCT. All patients received daily calcium and vitamin D supplements. We compared the changes in bone mineral density (BMD) in the lumbar spine, femoral neck and total hip at 6 and 12 months following allo-SCT between the control and treatment groups. We also assessed relationships between bone loss and cumulative glucocorticoid dose, cumulative tacrolimus dose and acute and chronic graft-versus-host disease (GVHD) by linear regression. In all, 78 patients were enrolled. The treatment group had significantly less BMD loss in the lumbar spine at 6 months (mean percent change 0.06±4.03 (treatment group) versus -2.61±4.2 (control group)) and 12 months (mean percent change 1.27±5.29 (treatment group) versus -1.81±4.49 (control group)) than the control group (P=0.03). Both groups lost more BMD in the femoral neck and total hip than in the lumbar spine at 6 and 12 months. The changes in BMD in the femoral neck and total hip did not differ significantly between groups. Both glucocorticoids and tacrolimus reduced BMD in the lumbar spine, but ibandronate prevented this loss. Ibandronate may reduce bone loss in the lumbar spine in patients who undergo allo-SCT, particularly those who have received high doses of glucocorticoids and/or tacrolimus.

OP0075 Osteoporotic fracture risk assessment using frax following hematopoietic stem cell transplantation

Background Bone loss and fractures following hematopoietic stem cell transplantation (HSCT) is common,(1, 2) and identifying patients at high risk for osteoporotic fractures following HSCT remains challenging. In the general population, the World Health Organization fracture risk assessment tool - FRAX is utilized to estimate a patients 10-year probability of developing a major osteoporotic fracture and hip fracture.(3) However, the utility of the FRAX model in predicting fractures following HSCT has not been evaluated. Objectives To assess the predictive value of FRAX in osteoporotic fracture risk assessment following HSCT. Methods We conducted a retrospective cohort study of patients >18 years that received a HSCT at The University of Texas MD Anderson Cancer Center, from January 1, 2001 to December 31, 2010. Patients were considered to have entered the cohort at the time of HSCT. All patients were retrospectively followed until December 31, 2013 for assessment of osteoporotic fracture. Osteoporotic fractures following HSCT were identified using ICD-9 codes, and confirmed by radiology and physician documentation. FRAX probabilities were calculated from baseline information obtained by chart review. Results A total of 5,170 patients underwent a HSCT during the 10-year study period. During an average of 3.3 years of follow up, 10% of patients developed a fracture. Fracture rates were higher (14%) in patients that underwent an autologous HSCT in comparison to those that received an allogeneic HSCT (6%). Mean major osteoporotic fracture FRAX scores were significantly higher in individuals who sustained an osteoporotic fracture compared to individuals who did not. The area under the receiver operating characteristic curve at 5 and 10 years following the HSCT were 0.61 and 0.66 respectively (Figure). We assessed the ability of the FRAX model for prediction of osteoporotic fracture with and without considering death as a competing risk. The hazard ratios were similar for both models (HR, 2.63, 95% CI, 1.93, 3.59; HR, 2.54, 95% CI, 1.86, 3.47, respectively).Figure 1 Conclusions To the best of our knowledge, this is the first study to demonstrate that the FRAX model has modest discriminative ability in predicting osteoporotic fractures following HSCT. Further independent validation of our findings is necessary, before routinely using the FRAX model in clinical practice. References Pundole XN, Barbo AG, Lin H, Champlin RE, Lu H. Increased incidence of fractures in recipients of hematopoietic stem-cell transplantation. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2015;33(12):1364–70. Schimmer AD, Minden MD, Keating A. Osteoporosis after blood and marrow transplantation: clinical aspects. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation. 2000;6(2A):175–81. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2008;19(4):385–97. Disclosure of Interest None declared

Case of mediastinal epithelioid hemangioendothelioma associated with hypertrophic osteoarthropathy and literature review

Hypertrophic osteoarthropathy is commonly associated with malignancies of the lungs and stomach. A few cases associated with epithelioid hemangioendothelioma, a rare vascular soft tissue neoplasm, have been reported. Presented here is the first report of a case of hypertrophic osteoarthropathy as the initial symptom of epithelioid hemangioendothelioma of the mediastinum. A 64‐year‐old woman presented with pain around the long bones and diffuse puffiness of bilateral hands and feet. She had a history of multiple malignancies, all of which were in remission. She had clubbing of her fingernails and toenails. Her chest X‐ray was negative. A positron emission tomography (PET) scan performed showed metabolically active soft tissue that extensively infiltrated the mediastinum, with several sites of disease involving the pericardium. Mediastinal biopsy and subsequent pleural fluid cytology obtained by thoracocentesis was consistent with metastatic epithelioid hemangioendothelioma. Our case supports that the PET scan has a valuable role in localizing malignancies in such patients who present with hypertrophic osteoarthropathy and no lung or stomach involvement.

Baseline characteristics predictive of malignancy among patients presenting with lymphadenopathy: A cancer center experience

Context: Patients who present to tertiary cancer centers solely with radiologic evidence of lymphadenopathy often are diagnosed with malignancy, but it is unclear which baseline characteristics are predictive of a cancer diagnosis. Materials and Methods: We conducted a retrospective data review to determine baseline characteristics predictive of a cancer diagnosis and the optimal follow-up time for such patients. Results: Sixty-six adult patients with lymphadenopathy were evaluated. Thirty-six patients (55%) were diagnosed with cancer; the most common type was lymphoma. Cancer was diagnosed in 94%, 79%, and 70% of patients with supraclavicular, retroperitoneal, and abdominal lymphadenopathy, respectively. Increasing age and hypertension were associated with a cancer diagnosis in the multivariate analysis. The mean time to diagnosis was 15 days (range, 1-140 days). The average follow-up time was 18 months in patients without a cancer diagnosis. Conclusions: Patients presenting solely with lymphadenopathy at a cancer center have a higher likelihood of being diagnosed with cancer if they are at least 50 years old or have hypertension. Supraclavicular lymphadenopathy is highly associated with a malignant diagnosis. We suggest that patients presenting solely with lymphadenopathy should be followed-up for at least 6 months for a definitive diagnosis.