Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents

Author(s):  
Gizem Guner Ozenen ◽  
Serap Aksoylar ◽  
Damla Goksen ◽  
Salih Gozmen ◽  
Sukran Darcan ◽  
...  

Abstract Objectives The early and late complications after hematopoietic stem cell transplantation (HSCT) determine the patients’ prognosis and life quality. We aim to determine the metabolic syndrome development frequency after HSCT in children to find out the risk factors and compare them with healthy adolescents. Methods Thirty-six children who underwent HSCT at least two years ago were analyzed prospectively and cross-sectionally. Our study included 18 healthy children between the ages of 11 and 17 as a control group. All of the cases were assessed in terms of metabolic syndrome (MS) through the use of Modified WHO Criteria. Results The patients’ median age was 10.6 (5.1–17) years, the median time of follow-up after HCST was 4.1 (2–13.5) years and 70% were male. Two cases were diagnosed with MS (5.6%). When considered in terms of the sub-components of MS, 2 cases (5.6%) were found to have obesity, 17 cases (47%) abnormal glucose tolerance, 11 cases (30.7%) dyslipidemia, and 3 cases (8.6%) hypertension. The MS rate was not different when compared with the 11–17 year-old healthy control group (0 vs. 11%, p=0.48). Myeloablative conditioning regimen (65 vs. 20%) and the increased age at which HSCT was performed were considered to be risk factors in terms of insulin resistance (p=0.025 and 0.002). Conclusions Age and conditioning regimens were found to be the risk factors for insulin resistance development. The long-term follow-up of the cases who had undergone HSCT in childhood in terms of MS and its sub-components is important in order to increase life quality.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anar Gurbanov ◽  
Bora Gülhan ◽  
Barış Kuşkonmaz ◽  
Fatma Visal Okur ◽  
Duygu Uçkan Çetinkaya ◽  
...  

Abstract Background and Aims The aim of the study is to investigate the incidence and risk factors of hypertension (HT) and chronic kidney disease (CKD) in patients who had hematopoietic stem cell transplantation (HSCT) during their childhood. Method Patients who had HSCT between January 2010-2019 with a minimum follow-up period of 6 months were included in the study. Data regarding renal complications were collected from the medical records of the patients. Guidelines of European Society of Hypertension (ESH) and American Academy of Pediatrics (APA) were used for the evaluation of hypertension. 24-hr ambulatory blood pressure monitoring (ABPM) was performed in children older than 5 years of age (68 patients). Ambulatory hypertension is diagnosed when systolic and/or diastolic blood pressure (BP) load is higher than 25%. Ambulatory prehypertension is diagnosed when mean systolic and/or diastolic BP is less than 95th percentile with systolic and/or diastolic BP load higher than 25%. Results A total of 72 patients (41 males and 31 females) were included in the study. The mean age of the patients at last visit was 10.8±4 years. ABPM revealed ambulatory HT in 6 patients (8.8%) and ambulatory prehypertension in 12 patients (17.6%). Office BP revealed HT in 3 patients (4.2%) and increased BP in four patients (5.6%) according to APA guideline (2017). In cohort, 12 patients with normal office BP (according to APA guideline) had ambulatory prehypertension or hypertension with ABPM. Office BP revealed HT in 1 patient (1.4%) and high-normal BP in 3 patients (4.2%) according to ESH guideline. In cohort, 15 patients with normal office BP (according to ESH guideline) had ambulatory prehypertension or hypertension with ABPM (Table 1). After a mean follow-up period of 4.4±2.5 years, CKD developed in 8 patients (11.1%). Patients with chronic graft-versus-host disease, with HLA-mismatched HSCT and/or transplantation of peripheric or cord blood hematopoietic stem cells had increased risk of CKD (p=0.041, p=0.033 and p=0.002, respectively). Conclusion Patients with HSCT should be regularly followed for the development of HT and ABPM should be used on regular basis. Patients with risk factors should be closely monitored for the development of CKD.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2732-2732
Author(s):  
Giorgio Lambertenghi Deliliers ◽  
Lorena Airaghi ◽  
Patrizia Usardi ◽  
Alessandra Orsatti ◽  
Marina Baldini ◽  
...  

Abstract Metabolic syndrome (MS), formerly known as X-syndrome, is a clinical and laboratory entity involving obesity, hypertension, and borderline fasting glucose, high triglyceride and low HDL cholesterol levels, that is considered to be a counterpart of insulin resistance with overweight playing a key role; increased insulin, leptin, adiponectin and resistin levels link its various features and some common flanking findings such as hypercholesterolemia, hyperuricemia and hyperferritinemia. Clinical and laboratory data reminiscent of metabolic syndrome are commonly observed after hematopoietic stem cell transplantation (HSCT). We evaluated the body mass index (BMI), routine lipid and glucidic markers, and common endocrinologic parameters in 37 HSCT recipients (19 males; median age 45 years, range 26–60; 22 autologous, 15 allogeneic) whose continuous CR lasted at least five years; insulin (baseline and after an oral glucose test), leptin, resistin, TNF-alpha and adiponectin levels were also detemined. Diabetic HSCT recipients were excluded. The control group consisted of 23 healthy volunteers of comparable age and sex without a family history of diabetes. In comparison with the controls, the HSCT recipients had significantly increased levels of TNF (median 10.05 vs 9.3 pg/mL, p=0.034), insulin (13.6 vs 10.1 mIU/mL, p=0.029) and leptin (13.71 vs 3.69 ng/mL, p= 0.02); there were no significant differences in adiponectin and resistin levels, BMI or the other considered parameters. In comparison with the other HSCT recipients, the 16 patients with higher baseline insulin levels (>15 mIU/mL) had significantly higher leptin levels (median 23.665 vs 8.3, p<0.001), and also different total cholesterol (231 vs 202 mg/dL, p<0.01), HDL-cholesterol (58 vs 68 mg/dL, p<0.01), triglyceride (150 vs 92 mg/dL, p<0.01) and ferritin levels (635 vs 491 ng/mL, p<0.01). This preliminary investigation show an increased prevalence of MS findings in HSCT recipients, and a relationship between baseline insulin levels and some common laboratory features of MS. Unlike in spontaneously occurring cases, obesity does not seem to play a primary role; furthermore, BMI and adiponectin were not significantly increased. However, the significant increase in TNF (another inducer of insulin resistance) suggests a possible pathogenetic sequence of post-HSCT MS linking TNF, insulin and leptin. The association between MS and the development of cardiovascular diseases is well known, but HSCT may, in alternative ways, induce a long-term metabolic derangement that affects the life expectancy of patients already cured of their baseline neoplastic disease.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2512-2512
Author(s):  
Meng Wang ◽  
Wenjia Wang ◽  
Ayesha Abeywardane ◽  
Malinthi Adikarama ◽  
Donal McLornan ◽  
...  

Abstract Introduction Autoimmune hemolytic anemia (AIHA) is the most commonly reported autoimmune complication following hematopoietic stem cell transplantation (HSCT) with incidence of 2-6%. The risk factors and pathogenesis remain poorly understood. Treatment often requires multiple therapeutic agents with variable efficacy and outcome. However no study to date has shown whether AIHA directly results in increased mortality. In order to better understand the risk factors, mortality and management of post-HSCT AIHA, we carried out a retrospective analysis of 533 allogeneic HSCTs in adult patients performed at King's College Hospital between 2005-2011. Method The median follow-up period after HSCT was 31 months (range 2.9 – 100 months). The primary endpoint was the onset of AIHA, defined by positive direct agglutinin test (DAT) arising after the HSCT, with biochemical markers of hemolysis (raised serum lactate dehydrogenase (LDH), reduced haptoglobin, or spherocytes on the blood film). Hemolysis was considered significant if the drop in hemoglobin was more than 20 g/l. Cases of DAT positivity due to ABO antibodies, as well as those with history of AIHA or positive DAT prior to HSCT were excluded. Potential risk factors for development of AIHA were calculated with univariate followed by multivariate analysis comparisons of incidence of AIHA for each clinical stratum. Kaplan-Meier method was used to compare mortality caused by AIHA against overall mortality (OM), and transplant-related mortality (TRM). AIHA was modelled as a time-dependent variable when estimating mortality. All patients alive at last follow-up who did not develop AIHA were censored. Results We identified 19 cases of AIHA following HSCT (overall incidence 3.6%). The median time to onset from HSCT to AIHA was 202 days. AIHA was associated with HSCT from unrelated donors (p = 0.026; Hazard Ratio = 5.28, 95% CI = 1.22 – 22.9), and concordant sex between HSCT recipients and donors (p = 0.045; Hazard Ratio = 3.52; 95% CI = 1.03 – 12.1). No significant association was observed between AIHA and the following eight factors: recipient gender; primary hematological disease; source of hematopoietic stem cells; conditioning regimen (alemtuzumab/ATG versus non-alemtuzumab/ATG, and reduced intensity versus myeloablative); HLA mismatch between donor/recipient; ABO mismatch; recipient CMV status; and concurrent chronic GvHD. AIHA patients also exhibited high frequency of simultaneous alloimmunization to Rh antigens coinciding with the onset of AIHA, which was not due to difference in transfusion rates, and not observed in the population who tested negative for DAT. Majority of AIHA patients (14/19; 72%) required multiple agents for treatment, but only 9/19 (47%) cases achieved complete resolution of AIHA (1 with intravenous immunoglobulin; 2 with prednisolone alone; 6 with rituximab in combination with other agents). The median survival from onset of AIHA was 487 days (range 26 – 1977 days). We compared the mortality of the AIHA versus non-AIHA population that survived beyond the median time of onset for AIHA (202 days). Patients with post-transplant AIHA had a higher OM (p = 0.006, Hazard Ratio = 2.37, 95% CI = 1.28 – 4.39), 1-year OM of 22% versus 10% (p = 0.04) and 1-year TRM of 18% versus 4% (p = 0.001), respectively (Figure 1). 36% (4/11 cases) of deaths were attributable to AIHA. Conclusion The overall incidence of AIHA following allogeneic HSCT in our study was 3.6%. The risk factors associated with AIHA were receiving HSCT from unrelated donors, and matched gender between the donor/recipient, which has not been previously reported. We observed an association between allo and autoimmunization in the AIHA patients, suggesting a common immune defect underlying both phenomena. The most effective treatment was a combination regimen of rituximab with prednisolone or other immunosuppressive agents. The overall mortality rate for our AIHA patients was high at 53% (10/19 cases), with AIHA as a cause of death in 36% of deceased patients. We have shown that AIHA following HSCTs indeed leads to increased mortality with over 2 fold higher OM in the patients with AIHA. Figure 1 Figure 1. Disclosures McLornan: Novartis: Research Funding.


Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 125-133 ◽  
Author(s):  
André Tichelli ◽  
Alicia Rovó ◽  
Alois Gratwohl

Abstract Non-malignant late effects after hematopoietic stem cell transplantation (HSCT) are heterogeneous in nature and intensity. The type and severity of the late complications depend on the type of transplantation and the conditioning regimen applied. Based on the most recent knowledge, we discuss three typical non-malignant complications in long-term survivors after HSCT, namely pulmonary, cardiovascular and renal complications. These complications illustrate perfectly the great diversity in respect of frequency, time of appearance, risk factors, and outcome. Respiratory tract complications are frequent, appear usually within the first two years, are closely related to chronic graft-versus-host disease (GVHD) and are often of poor prognosis. Cardiac and cardiovascular complications are mainly related to cardiotoxic chemotherapy and total body irradiation, and to the increase of cardiovascular risk factors. They appear very late after HSCT, with a low magnitude of risk during the first decade. However, their incidence might increase significantly with longer follow-up. The chronic kidney diseases are usually asymptomatic until end stage disease, occur within the first decade after HSCT, and are mainly related with the use of nephrotoxic drugs such as calcineurin inhibitors. We will discuss the practical screening recommendations that could assist practitioner in the follow-up of long-term survivors after HSCT.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4877-4877
Author(s):  
Yingyao Chen ◽  
Jun Xu ◽  
Zhiping Fan ◽  
Na Xu ◽  
Fen Huang ◽  
...  

Abstract Objective: To explore the incidence, clinical features,risk factors and survival prognosis of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by using large samples form a single center.Provide a prerequisite for improving the early diagnosis of BOS after allo-HSCT. Methods: We retrospectively investigated the case data of 802 patients who underwent allo-HSCT in our institute in petiod of January 1, 2015 to December 31, 2019 and survived more than 100 days. Adopt a multidisciplinary discussion method in the Department of Hematology, Respiratory and Radiology,according to the 2014 National Institutes of Health (NIH) ,diagnose and assess the severity of patiencts with BOS.Describe the clinical characteristics of BOS, and then analyze the risk factors and survival prognosis. Result: Among the 802 patients,46 patients(5.74%), 26males and 20 females with a median age of 32 years was diagnosed BOS.The median time to first appearance of respiratory symptoms was 13.5 months after transplantation, and the median time to diagnosis was 14.4 months.The cumulative incidence rate for 1- year, 2- year, and 5 -year after allo-HSCT is 3.7%, 6.5%, and 8.4%,while the cumulative incidence rate for patients already diagnosed with cGVHD is 7.5%、12.4% and 15.0% . Univariate analysis showed several risk factors associated with the onset of BOS,including the presence of preoperative or postoperative pneumonia,free of ATG ,use of DLI,peripheral blood stem cell transplantation, occurrence of GVHD and the severity and number of these episodes .And multivariate analysis denotes :free of ATG ,use of DLI,and number of organs affected by cGVHD were the variables correlated with increased incidences of BOS. At the onset of BOS, FEV1, FEV1%pred, FEV1/FVC ,FEV1/FVC %pred were significantly lower than those before transplantation. Compare before and after onset, the average decrease rate of FEV1 is 0.17L/month, while FEV1%pred is 5.15%/month.We also recorded the last follow-up lung function to evaluate the treatment efficacy : after treatment, the average FEV1 was 2.46L, the average of FEV1%pred was 36.61%, the average of FEV1/FVC was 45.80%, and the average of FEV1/FVC%pred was 56.36%, before and after treatment., FEV1%pred has no statistical difference (P=0.455).Not only that, there was no statistical difference in the treatment effect among different severity of BOS.The median follow-up time after the diagnosis of BOS was 19 months, and there was no statistical difference in the survival rate between the BOS and non-BOS groups at the end of the follow-up. The analysis result shows that early-onset BOS is a independent risk factors for poor survival time of BOS.Compare BOS with other non-infectious lung complications,the severity of BOS and cGVHD involving extrapulmonary organs are statistically different. Conclusion: BOS is a serious refractory complication after allo-HSCT.Early detection of potential patients with BOS is very difficult , and because most of the BOS patients did not respond to the therapy well, eventually lead to the irreversibility of deterioration of PFT. Compared with other non-infectious lung complications, strong association with severe cGVHD and deterioration of lung function characterized by obstructive ventilation disorder,etc.It suggests that the clinical need to deepen the recognition of BOS, continue to explore the early diagnosis method of BOS , more importantly , strive to give effective treatment at the early stage to improve the prognosis. KEYWORDS Bronchiolitis obliterans Allogeneic hematopoietic stem cell transplantation Risk factors Non-infectious pulmonary complications Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3463-3471 ◽  
Author(s):  
André Tichelli ◽  
Christoph Bucher ◽  
Alicia Rovó ◽  
Georg Stussi ◽  
Martin Stern ◽  
...  

Abstract We assessed incidence and risk factors of cardiovascular events in 265 patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) between 1980 and 2000 and who survived at least 2 years. Results were compared with a cohort of 145 patients treated during the same period with autologous HSCT. The median age of patients with allogeneic HSCT at last follow-up was 39 years, and median follow-up was 9 years. Eighteen (6.8%) patients after allogeneic and 3 (2.1%) patients after autologous HSCT experienced an arterial event. The cumulative incidence of first arterial event after allogeneic HSCT was 22.1% (95% CI, 12.0-40.9) at 25 years. The cumulative incidence 15 years after allogeneic HSCT was 7.5% as compared with 2.3% after autologous HSCT. Adjusting for age, risk of an arterial event was significantly higher after allogeneic HSCT (RR 6.92; P =.009). In multivariate analysis, allogeneic HSCT (RR: 14.5; P =.003), and at least 2 of 4 cardiovascular risk factors (hypertension, dyslipidemia, diabetes, obesity) (RR: 12.4; P =.02) were associated with a higher incidence of arterial events after HSCT. Thus, long-term survivors after allogeneic HSCT are at high risk for premature arterial vascular disease. HSCT might favor the emergence of established risk factors, such as hypertension, diabetes, and dyslipidemia.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1786
Author(s):  
Anu Haavisto ◽  
Sidsel Mathiesen ◽  
Anu Suominen ◽  
Päivi Lähteenmäki ◽  
Kaspar Sørensen ◽  
...  

There are many known endocrine complications after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood including increased risk of biochemical hypogonadism. However, little is known about sexuality in adulthood following childhood HSCT. In this multicenter study, sexual functions and possible risk factors were assessed comprehensively in two national cohorts (Finland and Denmark) of male adult survivors of childhood HSCT. Compared to a healthy control group (n = 56), HSCT survivors (n = 97) reported less sexual fantasies, poorer orgasms, lower sexual activity with a partner and reduced satisfaction with their sex life, even in the presence of normal erectile functions and a similar frequency of autoerotic acts. Of the HSCT survivors, 35% were cohabitating/married and 66% were sexually active. Risk factors for poorer self-reported sexual functions were partner status (not cohabitating with a partner), depressive symptoms, CNS and testicular irradiation. Sexual dysfunction increased by age in the HSCT group with a pace comparable to that of the control group. However, because of the lower baseline level of sexual functions in the HSCT group, they will reach the level of clinically significant dysfunction at a younger age. Hence, male survivors of childhood HSCT should be interviewed in detail about their sexual health beyond erectile functions.


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