Alterations of Nutritional Status in Children and Adolescents with Acute Lymphoblastic Leukemia.

Malnutrition is often observed in pediatric cancer patients and has been recognized as a risk factor for relapse and survival. Maintaining an appropriate nutritional status during anticancer treatment has, therefore, been more and more frequently perceived as an additional requirement for optimal therapy outcomes. The aim of our study was to establish alterations of nutritional status in 26 children and adolescents treated for acute lymphoblastic leukemia (ALL) at the Children's Hospital in Zagreb, Croatia, between 2016 and 2021, by using anthropometric measures and serum albumin levels. The majority of patients (53.8% female, median 4 years, 52.2% intermediate-risk leukemia group) had normal weight at the beginning of chemotherapy. The percentage of overweight/obese patients increased from 4.2% at diagnosis to 37.5% at the end of intensive therapy. Apart from a significant increase in body weight (BW) and body mass index (BMI) for age, a notable decline in body height/body length (BH/BL) for age in the observed period was recorded, especially in high-risk leukemia patients. The alterations in serum albumin values were not significant, nor was their correlation with BMI. Dietary consultation was offered to all patients, while children with a decline in BMI and BH/BL received additional nutritional support.

Management of Childhood Iron Deficiency Anemia in a Developed Country-A Multi-Center Experience from Croatia.

Iron deficiency anemia (IDA) continues to be a global public health concern, mostly in the developing countries. However, precise epidemiological data on childhood IDA in Croatia are lacking. In order to establish its frequency, underlying etiologies, the rationale for tertiary care visits, diagnostic practices, and current treatment regimens of IDA, medical records of children referred to pediatric hematologists for iron deficiency in a five-year period at tertiary institutions (Zagreb, Rijeka, Split, Osijek) throughout Croatia were retrospectively analyzed. Eight hundred and sixty-four children, predominately of preschool age, were referred mainly by the primary care pediatricians, who, in general, performed basic diagnostics but failed to initiate oral iron therapy in half of the patients. Approximately one-third of patients were symptomatic, with inadequate nutrition prevailing as underlying etiology. Dextriferron was the preferred iron formulation among hematologists, with a median dose of 5 mg/kg, with acceptable compliance rates (63.5-93.2%). Hospital admission rates varied among the centers (9.4-35%), and so did transfusion policies (6.4-22.9%). The greatest difference was observed in the frequency of parenteral iron administration (0.3-21.5%). In conclusion, the burden of childhood IDA, even in a high-income country, remains substantial, necessitating consistent implementation of national guidelines and additional education of primary health care providers.

The Burden of Childhood Iron Deficiency Anemia in a Developed Country: A Croatian Tertiary Care Center Experience.

BACKGROUND: Given the high prevalence of unrecognized iron deficiency anemia (IDA) in Croatia and its negative impact on children's somatic and neurological outcomes, a comprehensive preventive and treatment approach is a necessity.  Methods: This was an observational, cross-sectional study of pediatric patients referred to the Children's Hospital Zagreb, Croatia, from 2017 to 2021, for IDA. Epidemiological and clinical data were extracted. Laboratory workup and therapeutic actions in the primary and tertiary care settings were recorded. The need for transfusion, parenteral iron therapy, and hospital admission was noted. RESULTS: A total of 299 patients (52.2% female, median five years) were seen by the hematologist in the five-year study period. Almost half (45.1%) were referred by the primary care pediatrician. Only half of the patients (56.6%) received oral iron therapy prior to referral. The preferred preparation was Dextriferron (67.7%) during the mean period of 5.8 months, but more than one-third of the patients (36.5%) were non-compliant. Every 10th child seen by the hematologist for IDA was admitted to the hospital; 6.4% required transfusion therapy, and in only one patient, parenteral iron was administered.  Conclusions: The results of this survey established that IDA still represents an excessive burden in a tertiary care setting of a high-income country. Therefore, consistent implementation of national guidelines and additional education of primary healthcare providers is crucial to ameliorate this significant public health concern.

Complementary Medicine Practice and Use of Dietary Supplements in Pediatric Cancer Patients in Croatia.

INTRODUCTION:  The use of complementary and alternative medicine (CAM) has become a customary practice among pediatric cancer patients worldwide. The frequency of its use by pediatric cancer patients in Croatia has not been previously determined.  Methodology: In order to establish the frequency and detect factors affecting the use of CAM, a single-center, observational, cross-sectional study was conducted at the Children's Hospital Zagreb during a two-year period. The patients' parents and caregivers were offered an anonymous, multi-item questionnaire that collected socio-economic and clinical data, as well as details on CAM and dietary supplement practice.  Results: Almost half of the participants reported CAM and more than two-thirds reported dietary supplement consumption, predominantly in the intensive phase of the treatment. Factors regarding children or parents had no effect on CAM and supplement utilization. Herbal medicine, vitamins, and minerals were among the most commonly used items. Every 10th child experienced at least one adverse event during CAM and supplement use. CONCLUSION:  Awareness of the CAM and dietary supplement application in pediatric oncology patients needs to be raised due to the potential interactions with conventional treatment modalities. For this reason, it is extremely important to inform parents and caregivers of pediatric oncology patients about the use of CAM and dietary supplements to predict and mitigate the occurrence and intensity of the side effects. In the majority of our cases, the patient's guardians informed the healthcare professionals about the CAM and supplement implementation in their children, therefore, they were offered additional information about the possible negative impact of CAM and supplement use on standard medical care in a timely manner.

Does transitory steroid-induced central hypothyroidism in children treated for haematological malignancies warrant clinical intervention?

INTRODUCTION: Steroid-induced central hypothyroidism (CH) is a frequent but under-diagnosed hormonal disturbance in children treated for acute lymphoblastic leukaemia (ALL) and lymphoma. AIM OF THE STUDY: To determine the occurrence, frequency of symptoms, replacement therapy administration, and association of CH with glucocorticoid therapy in children treated for haematological malignancies. MATERIAL AND METHODS: A prospective clinical survey was conducted on 21 patients (61.9% male, mean age 9.1 years) treated in the Children's Hospital Zagreb during 2019, of whom 12 were treated for for ALL and 6 for Hodgkin lymphoma (HL), based on clinical (signs and symptoms) and laboratory data (hormonal status). RESULTS: Overt CH was verified in 15 (71.4%) and mild CH in 3 patients (14.2%). The most common symptoms and signs were fatigue, apathy, and electrolyte imbalance, observed in 50% of CH cases. Hormonal substitutional therapy was initiated in 44.4% of affected patients, during a mean of 2.08 months, with significant clinical improvement. Overt CH was more prevalent in patients with ALL than in those with HL (p = 0.025). Among children with ALL there was no difference in CH occurrence between the prednisone and dexamethasone groups; however, dexamethasone-induced CH was more frequently symptomatic (p = 0.03). The prednisone dosage played no role in CH incidence in patients with HL. CONCLUSIONS: Further studies are needed to determine the real incidence of thyroid dysfunction during intensive chemotherapy treatment in children with ALL and lymphoma. Recommendations for optimal hormonal replacement therapy and a follow-up plan for paediatric oncology patients with CH are also urgently required.

A challenging case of an adolescent and young adult patient with high-risk acute lymphoblastic leukemia: the need for a multidisciplinary approach: a case report.

BACKGROUND: Adolescents and young adults diagnosed with acute lymphoblastic leukemia are treated according to pediatric-based regimens to achieve better results. However, implementation of intensive chemotherapy protocols in this age group is associated with increased treatment-related toxicities, affecting almost every organ and system. In this case, the focus of our interest was on rather rare entities: steroid-induced psychosis that seldom develops in children and adolescents, and choroid plexus hemosiderosis, infrequently identified as a first sign of iron overload. CASE PRESENTATION: The aim of this paper is to present a challenging case of a 15-year-old Caucasian male patient treated for high-risk acute lymphoblastic leukemia and who experienced various adverse incidents during intensive chemotherapy, thus necessitating a high-quality multidisciplinary approach. Slow minimal residual disease clearance was an additional concerning issue. Induction and re-induction were complicated by steroid-induced hyperglycemia that required multiple-week insulin. During consolidation, acute kidney injury on the basis of chronic kidney disease was verified, demanding subsequent drug dose modifications. By the end of re-induction, after dexamethasone cessation, infrequent steroid-induced psychosis, presented as incoherent speech, aggressive behavior, and mood swings, required intensive psychiatric support. Neurological evaluation of seizures revealed uncommon choroid plexus hemosiderosis by brain magnetic resonance imaging, warranting appropriate selection of iron chelation therapy in the context of preexisting nephropathy. Ultimately, iron deposits of moderate intensity were verified by liver magnetic resonance imaging, while heart tissue remained intact. The early diagnosis and adequate treatment of aforementioned difficult toxicities resulted in complete recovery of the patient. CONCLUSIONS: Treating adolescents with high-risk acute leukemia and multiple therapy-related morbidities remains a challenge, even in the era of extensive and effective supportive therapy. Superior survival rates might be achieved by prompt recognition of both frequent and rarely encountered adverse episodes, as well as well-timed and appropriate management by a well-coordinated multidisciplinary team.

INVASIVE FUNGAL INFECTIONS IN CHILDREN TREATED FOR HEMATOLOGIC MALIGNANCIES - A FIVE-YEAR SINGLE CENTER EXPERIENCE.

Invasive fungal infections (IFI) are life-threatening complications of intensive chemotherapy treatment, with the incidence in pediatric patients ranging from 2% to 21%. In this article, we describe our 5-year experience of IFI in pediatric oncology patients and its clinical manifestations with radiological findings, treatment and outcome. A retrospective and descriptive survey of IFI in children with hematologic neoplasms was conducted at the Department of Oncology and Hematology, Zagreb Children's Hospital. Medical charts of children 0-17 years of age, of both sexes, treated for leukemias and lymphomas from January 2016 to December 2020 were reviewed. In a 5-year period, 60 patients were treated for hematologic malignancy, acute lymphoblastic leukemia (ALL) being the most prevalent diagnosis. IFI was verified in 9 (15%) children, predominantly in patients with ALL (75%). The specific causative agent was detected in one child, whereas other infections were classified as probable pulmonary aspergillosis. All the patients received standard prophylaxis with fluconazole and treatment with liposomal amphotericin B and voriconazole. The majority of our patients achieved recovery. IFI prevention, diagnosis and treatment remain a challenge. Uniform prophylaxis and therapy protocols, as well as environmental control are of vital importance for the development of better strategies in the prevention, early detection and treatment of IFI in pediatric hematology patients.

Nutritional status as a predictor of adverse events and survival in pediatric autologous stem cell transplant.

Nutritional status is recognized as an independent and modifiable risk factor of outcome in stem cell transplant. Our research aim was to evaluate the impact of body mass index (BMI) and serum albumin on the prevalence of adverse events and survival in autologous transplant in children. A retrospective study was conducted of autologous transplants performed between 2006 and 2017 in the Children's Hospital Zagreb, Croatia. Nutritional status was assessed at the times of diagnosis, procedure, and discharge using BMI (underweight, normal, obese) and serum albumin (grades 1-4). Adverse events (fever, gastrointestinal toxicity, electrolyte disturbances, dysglycemia) and outcome (3-year, relapse, mortality) were documented. Seventy-seven children (54.5% males, mean age 7.9 years) underwent autologous transplant, mostly for neuroblastoma. In terms of BMI and albumin, which showed significant positive correlation at diagnosis (p = 0.026) and transplant (p = 0.016), most participants were well nourished. Average post-transplant weight loss was 4%. Major toxicities were severe mucositis (72.7%) and hypophosphatemia (31.2%). Relapse and mortality rates were 35.1% and 42.9%, respectively. Hypokalemia (p = 0.041) and hypomagnesemia (p = 0.044) were more prevalent in the underweight group, while obese children experienced significantly less severe mucositis (p = 0.016) and hypophosphatemia (p = 0.038). There was no significant difference regarding outcome among children of different nutritional status, although undernourished children tended to have lower relapse and mortality rates. In conclusion, underweight children are significantly more prone to severe electrolyte disorders and mucositis, and although statistical significance was not reached, are more likely to survive.

Perinatal outcome of singleton versus twin late preterm infants: do twins mature faster than singletons?

OBJECTIVE: To determine whether as a result of an assumed advanced maturation late preterm twin infants have a more favorable perinatal outcome than singleton late preterm infants. METHODS: Over a 36-month period (from September 2011 to September 2014), 277 late preterm infants (153 from singleton and 124 from twin pregnancies) were hospitalised in NICU, University Hospital Center "Sisters of Mercy" Zagreb, Croatia, and were retrospectively studied by review of maternal and neonatal charts for gestational age, sex, birth weight, mode of delivery, 5-min Apgar score and for several outcome variables expected for preterm infants, until the day of discharge. RESULTS: There was statistically no significant difference in the incidence of any of the observed and compared outcomes, except in the incidence of phototherapy which was higher in singletons group (49.01 versus 13.7%, p < 0.0001). The mean birth weight, as expected, was smaller in the twin group. CONCLUSIONS: We found no evidence to support the traditional belief that twin late preterm infants have accelerated maturation and better neonatal outcome compared with singleton late preterm infants. Our findings suggest that late preterm twins have a prognosis similar to that of singleton late preterm infants born at the same gestational age.