Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia (original) (raw)
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Turkish Journal of Hematology, 2017
Amaç: Akut lenfoblastik lösemili (ALL) hastalardaki sağ kalım oranlarının artışı, tedavi sonrası ortaya çıkan morbidite ve mortalite problemlerinin takip edilme ihtiyacını beraberinde getirmiştir. Çalışmamızda, en az iki yıldır remisyonda olan ALL'li hastalarda, tedavi sonrası ortaya çıkabilecek endokrin komplikasyonların değerlendirilmesi amaçlandı. Gereç ve Yöntemler: ALL tanısı ile tedavi almış ve tedavisi üzerinden en az iki yıl geçmiş ve remisyonda olan 60 hastada endokrin geç komplikasyonlar kesitsel olarak değerlendirildi. Bulgular: Hastaların tanı aldıkları andaki median yaşları 5 yıl (minimum-maksimum: 1,7-13), kemoterapi sonlandırıldığı andaki median yaşları 8 yıl (minimum-maksimum: 4,25-16), çalışma sırasındaki median yaşları ise 11,7 yıl (minimum-maksimum: 7-22) olarak tespit edildi. Hastaların tedavi sonrası median takip süresi ise 4 yıl (minimum-maksimum: 2-10,1) idi. Hastaların %81,6'sında en az bir endokrin komplikasyon geliştiği görüldü. D vitamini eksikliği/ yetersizliği (%46,6), obezite/fazla kiloluluk (%33,3) ve dislipidemi (%23,3) en sık gelişen üç komplikasyon olarak tespit edildi. D vitamini eksikliğine sekonder gelişen hiperparatiroidi (%15), insülin direnci (%11,7), hipertansiyon (%8,3), boy kısalığı (%6,7), tiroid fonksiyon bozukluğu (%5), puberte prekoks (%3,3) ve azalmış kemik mineral yoğunluğu (%1,7) gelişen diğer endokrin komplikasyonlardı. Hastalarda gelişen endokrin komplikasyonlar arasında cinsiyet, yaş, radyoterapi bakımından farklılık saptanmaz iken, D vitamini yetersizliği/eksikliği saptanan hasta sayısı pubertal grupta, prepubertal gruba göre anlamlı derecede fazlaydı (%57,5 ve %25, sırasıyla, p=0,011). Sonuç: Çalışmamızda yüksek oranda endokrin komplikasyon saptandı. Bu komplikasyonlar, geç yan etkilerin ortaya çıkmasına neden olabilecek yüksek risk özellikleri ve sıklığı tanımlayabilmek, erken tanı ve önleyici stratejileri geliştirmek açısından hastaların uzun dönem izlenmelerini gerektirmektedir. Anahtar Sözcükler: Akut lenfoblastik lösemi, Endokrin, Geç yan etkiler, Çocuk Objective: Improvement in long-term survival in patients with acute lymphoblastic leukemia (ALL) in childhood has led to the need for monitorization of treatment-related morbidity and mortality. In the current study, we aimed to evaluate endocrine side effects of treatment in ALL survivors who were in remission for at least 2 years. Materials and Methods: Sixty patients diagnosed with ALL, who were in remission for at least 2 years, were cross-sectionally evaluated for long-term endocrine complications. Results: The median age of the patients at the time of diagnosis, at the time of chemotherapy completion, and at the time of the study was 5 years (minimum-maximum: 1.7-13), 8 years (minimummaximum: 4.25-16), and 11.7 years (minimum-maximum: 7-22), respectively, and median follow-up time was 4 years (minimummaximum: 2-10.1). At least one complication was observed in 81.6% of patients. Vitamin D insufficiency/deficiency (46.6%), overweight/ obesity (33.3%), and dyslipidemia (23.3%) were the three most frequent endocrine complications. Other complications seen in our patients were hyperparathyroidism secondary to vitamin D deficiency (15%), insulin resistance (11.7%), hypertension (8.3%), short stature (6.7%), thyroid function abnormality (5%), precocious puberty (3.3%), and decreased bone mineral density (1.7%). There were no statistically significant correlations between endocrine complications and age, sex, and radiotherapy, except vitamin D insufficiency/deficiency, which was significantly more frequent in pubertal ALL survivors compared to prepubertal ALL survivors (57.5% and 25%, respectively, p=0.011). Conclusion: A high frequency of endocrine complications was observed in the current study. The high frequency of late effects necessitates long-term surveillance of this population to better understand the incidence of late-occurring events and the defining of high-risk features that can facilitate developing intervention strategies for early detection and prevention.
Clinical Endocrinology, 2008
Background Treatments of acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL), involving various combinations of chemotherapy (chemo), cranial irradiation (CI) and/or bone marrow transplantation after total body irradiation (BMT/TBI), are often successful but may have several long-term harmful effects. Objective To evaluate late endocrine and metabolic complications in adult survivors of childhood ALL and NHL, in relation with the different therapeutic schemes received. Design Endocrine and metabolic parameters were determined in 94 patients (48 men, mean age: 24 ± 5 years) with a former childhood ALL (n = 78) or NHL (n = 16) and subgrouped according to their previous treatment: chemo only (group I; n = 44), chemo + CI (group II; n = 32) and chemo + BMT/TBI (group III; n = 18). Results Severe GH deficiency (peak < 3•0 ng/ml after glucagon) was observed in 22% and 50% of patients of groups II and III, respectively, while hypothyroidism was mainly observed in group III (56%). Moreover, 83% of men developed hypogonadism after BMT/TBI, compared to 17% and 8% in groups I and II, respectively (P < 0•05), and all grafted women had ovarian failure, in contrast with other female patients in whom menarche had occurred spontaneously. Patients with BMT/TBI had also an adverse metabolic profile, with insulin resistance in 83% and dyslipidaemia in 61%. Conclusions This study reveals a high prevalence of endocrine and metabolic disorders in young adult survivors of childhood ALL or NHL, this frequency mainly depending on the treatment received. Treatment with BMT/TBI is the most detrimental and many of these patients will develop GHD, hypothyroidism, hypogonadism, insulin resistance and dyslipidaemia.
The Journal of Clinical Endocrinology & Metabolism, 2004
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving longterm survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified.
Late endocrine side effects in children with acute leukemia
2007
This study was carried out in 28 patients (10 female, 18 male) diagnosed with acute leukemia, and aimed to investigate the abnormalities of endocrine system. Twenty-five of 28 patients were acute lymphoblastic leukemia and 3 were acute non-lymphocytic leukemia. Sixteen children were treated using BFM-90 chemotherapy protocol, and the rest with various regimens. Two patients were exposed to 12-13 Gy of total body irradiation followed by bone marrow transplantation. All patients were in remission at least five years. One (3%) of 28 patients had short stature and 4 (14%) had obesity. Pubertal status was retarded in 2 (7%) patients. Glucose intolerance, secondary hypothyroidism and hypergonadotropic hypogonadism were detected in 2, 1 and 2 patients, respectively. TSH response to TRH test was exaggerated in 1 and blunted in 3 patients.
Metabolic syndrome in the survivors of childhood acute lymphoblastic leukaemia
Obesity research & clinical practice, 2014
Metabolic syndrome is a common complication encountered in children surviving acute lymphoblastic leukaemia (ALL). Affected patients develop obesity, insulin resistance, hypertension, and hyperlipidemia. Metabolic syndrome is a consequence of multiple factors, particularly hormonal imbalance induced by various ALL treatments. This review aims to evaluate the risk factors and mechanisms leading to the development of metabolic syndrome. Further research is needed to improve our understanding of the mechanisms leading to insulin resistance and the associated endothelial and adipose tissue dysfunction. Future studies should also examine other possible contributing factors, such as environmental and genetic factors. Understanding these factors will help in guiding modifications of the current ALL treatment protocols in order to prevent the development of this syndrome and hence improve the quality of life of ALL survivors. Until this is achieved, clinicians should continue to identify pa...
Egyptian Pediatric Association Gazette, 2013
during therapy, one (8.3%) had pre-diabetes, seven (58.3%) had a risk level of Hb A1C but no one had diabetes mellitus (DM) or insulin resistance (IR). At study time the two survivors with transient hyperglycemia during therapy had a significantly high WHR compared to the remainders. WHR of the survivors at study time correlated significantly with fasting plasma glucose and area of insulin under the curve (AUC). The 2 h post-prandial plasma glucose correlated with the duration after therapy completion. Conclusions: WHR may play a better role than BMI in the prediction of insulin resistance in those patients. Hb A1C may increase earlier than other indices of glucose tolerance.
Endocrinological Analysis of 122 Japanese Childhood Cancer Survivors in a Single Hospital
Endocrine Journal, 2008
With recent improvements in the diagnosis and treatment of cancer, the number of childhood cancer survivors (CCSs) has been increasing in Japan. The importance of quality of life during the lifetime of CCSs has now been recognized, and the late effects of cancer treatments are essential and important issues. In this study we analyzed the endocrinological abnormalities of CCSs by retrospectively evaluating 122 outpatients (62 males and 60 females) who had been referred from pediatric oncologists to our follow-up clinic among 151 CCSs attending our hospital more than two years after their cancer treatment. Follow-up duration varied from 2 to 30 (median 8.0) years. Their average age was 17.3 (range 4-36, median 17.0) years, and 38 patients (31.1%) reached adulthood. Endocrinological abnormalities were found in 82 (67%) of 122 survivors. Gonadal dysfunction was observed in 60 patients (49%). Thirty-nine patients (32%) were short or grew at a slower rate. Twenty-six patients (21%) showed thyroid dysfunction. Other abnormalities were as follows: obesity in 20 patients (16%), leanness in 10 (8%), central diabetes insipidus in 11 (9%) and adrenocortical dysfunction in 9 (7%). Low bone mineral density was observed in 41 (42%) of 98 patients evaluated. These endocrinological abnormalities were caused by the combined effects of cancer itself and various treatments (chemotherapy, radiation therapy, surgery, and hematopoietic stem cell transplantation). Lifetime medical surveillance and continuous follow-up are necessary for CCSs, because treatment-related complications may occur during childhood and many years after the therapy as well. Endocrinologists should participate in long-term follow-up of these survivors in collaboration with pediatric oncologists.
Haematologica, 2016
C ardiovascular conditions are serious long-term complications of childhood acute leukemia. However, few studies have investigated the risk of metabolic syndrome, a known predictor of cardiovascular disease, in patients treated without hematopoietic stem cell transplantation. We describe the overall and age-specific prevalence, and the risk factors for metabolic syndrome and its components in the L.E.A. (Leucémie de l'Enfant et de l'Adolescent) French cohort of childhood acute leukemia survivors treated without hematopoietic stem cell transplantation. The study included 650 adult patients (mean age at evaluation: 24.2 years; mean follow-up after leukemia diagnosis: 16.0 years). The prevalence of metabolic syndrome was 6.9% (95% CI 5.1-9.2). The age-specific cumulative prevalence at 20, 25, 30 and 35 years of age was 1.3%, 6.1%, 10.8% and 22.4%, respectively. The prevalence of decreased high-density lipoprotein cholesterol, increased triglycerides, increased fasting glucose, increased blood pressure and increased abdominal circumference was 26.8%, 11.7%, 5.8%, 36.7% and 16.7%, respectively. Risk factors significantly associated with metabolic syndrome in the multivariate analysis were male sex (OR 2.64; 95% CI 1.32-5.29), age at last evaluation (OR 1.10; 95% CI 1.04-1.17) and body mass index at diagnosis (OR 1.15; 95% CI 1.01-1.32). The cumulative steroid dose was not a significant risk factor. Irradiated and non-irradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in non-irradiated patients. Survivors of childhood acute leukemia are at risk of metabolic syndrome, even when treated without hematopoietic stem cell transplantation or central nervous system irradiation. A preventive approach with regular screening for cardiovascular risk factors is recommended. clinicaltrials.gov identifier:01756599.