Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: A multicentre study.

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune-mediated destruction of haematopoietic cell lines. Effective and well-tolerated treatment options for relapsed-refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0-9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow-up and two of them had remission with low-dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed-refractory immune cytopenia.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study.

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

Timing of Central Venous Line Insertion During Induction in Children With Acute Lymphoblastic Leukemia.

PURPOSE: Central venous lines (CVL) in children with acute lymphoblastic leukemia (ALL) provide comfortable administration of intensive chemotherapy and blood sampling. The optimal time for the insertion of CVL in patients with ALL during induction therapy is controversial. This study aimed to investigate the frequency of CVL-related complications in children with ALL concerning the time of CVL insertion. PATIENTS AND METHODS: We reviewed the records of 52 pediatric ALL patients with CVL. CVL placement before or on treatment day 15 was defined as "early insertion", and after treatment day 15 was defined as "late insertion". Demographics, preoperative blood counts, type of central line, time of CVL placement, CVL-related complications, and blood counts during complications were all noted. All the data were collected from those with the first catheter use. RESULTS: CVL was placed ≤15 days in 26 patients (50%) and after 15 days in 26 patients (50%). Regarding the infection rates, no statistical difference was found between early and late CVL-inserted groups ( P =n.s.). Five patients developed thrombosis, and risk was found to be similar between early and late CVL-inserted groups ( P =n.s.). Catheter-related mechanical complications were recorded in 7 patients (3 in early and 4 in late CVL-inserted group, ( P =n.s.). CONCLUSION: The present study showed no relation between the timing of CVL placement during induction therapy and the occurrence of infection and thrombosis. Our results suggest that CVL can be placed safely at the time of diagnosis or early induction treatment to provide a comfortable administration of chemotherapy and decrease painful blood samplings.

Roles of Vitamin-K-dependent Factors Protein S and GAS6 With TAM Receptors and HMGB1 in Pediatric COVID-19 Disease.

OBJECTIVE: This study was designed to evaluate serum high-mobility group box 1 (HMGB1), protein S (PS), growth arrest-specific gene 6 (GAS6), and TAM receptor (TYRO3, AXL, and MERTK) levels in children with COVID-19 disease. METHODS: A prospective case-control study was conducted in our pediatric emergency department and 57 patients with SARS-CoV-2 polymerase chain reaction (PCR) positivity, 6 patients with multisystem inflammatory syndrome in children (MIS-C), and 17 healthy children were included. Demographic data, clinical findings, laboratory and radiologic data, the need for hospitalization, and prognosis were recorded. Serum HMGB1, PS, GAS6, and TAM receptor levels were studied by enzyme-linked immunosorbent assay method. RESULTS: While SARS-CoV-2 PCR-positive patients and healthy controls were similar in terms of gender and age, GAS6 and MERTK levels were significantly lower in SARS-CoV-2 PCR-positive patients compared with healthy controls. Among SARS-CoV-2 PCR-positive patients, no difference was found in terms of serum markers in those with and without gastrointestinal or respiratory system symptoms. However, in patients with respiratory distress at admission, PS and TYRO3 levels were significantly lower. AXL levels were lower in patients diagnosed with MIS-C compared with healthy controls. Activated partial thromboplastin time was negatively correlated with HMGB1, PS, GAS6, and AXL levels. CONCLUSION: Our results suggest that such measurements may be informative and warranted in children with COVID-19 who show evidence of coagulopathy and respiratory distress. Further studies are needed to clarify the roles of these markers in diagnosis, to predict clinical severity, and to evaluate their roles in treatment approaches for COVID-19 disease.

Evaluation of voriconazole related adverse events in pediatric patients with hematological malignancies.

BACKGROUND: Despite therapeutic drug monitoring and pharmacogenetic-guided dose selection are recommended for pediatric patients, safety of voriconazole is mostly monitored by clinical assessment. Having comprehensive knowledge of safety profile and distinguishing incidental events from the reactions that are truly related to voriconazole use are crucial for safer and uninterrupted treatment. OBJECTIVES: This study aimed to address adverse reactions during the first month of voriconazole use by systematically evaluating retrospective records of all adverse events. Patients/Methods: It is a single-center, retrospective analysis of patients who received voriconazole from 1 September 2010 to 1 September 2020. Severity of abnormal findings in medical records were systematically graded. Causality between voriconazole and the events was evaluated by Liverpool Causality Assessment Tool (LCAT), Naranjo Algorithm and World Health Organization Causality Assessment System. The events with possible or probable causal relation to voriconazole are classified as adverse reaction. RESULTS: Records of 45 patients included in the study. The overall frequency of adverse reactions was 51.1%. Hepatobiliary laboratory adverse reactions identified in 48.9% of the patients and led to treatment discontinuation in 20.0%. Amylase and lipase elevation (2.2%), ventricular extra systoles (2.2%), hallucination and nightmares (2.2%) were other adverse reactions. CONCLUSIONS: Hepatobiliary abnormalities were the most common adverse reactions and the most common cause of treatment discontinuation. For safer treatment in critically ill patients, the dose should be personalized. To clearly identify the accurate frequency and the causality of all adverse reactions, prospective studies with much larger sample size are needed.

Examination of the psychometric properties of pediatric-modified total neuropathy score in Turkish children with cancer.

BACKGROUND: Evaluation of chemotherapy-induced peripheral neuropathy has gained importance in symptom management of pediatric patients with cancer. This study aimed to perform the Turkish validity and reliability study of the Pediatric-Modified Total Neuropathy Score (Ped-mTNS). METHODS: A methodological, descriptive, and cross-sectional design was used in the study. Forty children aged between 5 and 18 and were treated for cancer and 40 age- and gender-matched healthy children (control group) were included in the study. The mean scores of the items on the Ped-mTNS were compared, and item-total score correlations were evaluated. Cronbach's alpha coefficient of the Ped-mTNS was calculated for internal consistency. FINDINGS: Cronbach's alpha value of the scale was found as 0.709. The item-total correlations of the scale items ranged from 0.260 to 0.658. The mean score of cancer patients on the Ped-mTNS was found as 4.4 ± 3.8. DISCUSSION: Ped-mTNS scores of children with cancer indicated more deficits than those of the control group. In the evaluation of children in the patient and control groups, a difference was found in terms of light touch sensation, which is one of the sensory symptoms in the items of the Ped-mTNS, and pin sensibility and strength, which are among the clinical symptoms. APPLICATION TO PRACTICE: The Ped-mTNS was determined to be a valid and reliable measurement tool for children with cancer aged between 5 and 18 in the Turkish population.

Evaluation of vincristine-induced peripheral neuropathy in children with cancer: Turkish validity and reliability study.

BACKGROUND: The evaluation of peripheral neuropathy in children receiving Vincristine treatment is challenging. This study examined the Turkish validity and reliability of the Total Neuropathy Score-Pediatric Vincristine (TNS-PV) measurement tool, which can measure Vincristine-induced peripheral neuropathy symptoms in children with cancer. METHODS: A total of 53 children aged 5-17 years who received Vincristine treatment in two pediatric hematology-oncology centers participated in the study. Data was collected using the Total Neuropathy Score-Pediatric Vincristine (TNS-PV), the Common Terminology Criteria for Adverse Events (CTCAE), the Wong-Baker FACES Pain Scale, and the Adolescent Pediatric Pain Tool (APPT). The correlation between the TNS-PV total score and other scales and the inter-rater reliability coefficient was evaluated. FINDINGS: Of the children, 81.1% were diagnosed with ALL and 13.2% with Ewing Sarcoma. Cronbach's alpha values of form A and B of the TNS-PV scale were 0.628 and 0.639, respectively. As the cumulative Vincristine dose increased, the children's scores on TNS-PV were higher. A moderate and significant positive correlation was found between the TNS-PV form A total score and the worst subjective symptoms a, b (A), strength, tendon reflexes, and autonomic / constipation (r = 0.441, r = 0.545, r = 0.472, r = 0.536, p < 0.01). DISCUSSION: The TNS-PV form B total score was found to have a moderate level, significant correlation with CTCAE sensory neuropathy score and Wong-Baker FACES Pain Scale, and a high level, significant positive correlation with CTCAE motor neuropathy score. APPLICATION TO PRACTICE: The TNS-PV is valid and reliable for measuring Vincristine-induced peripheral neuropathy in practice in Turkish children 5 years and older.

Evaluation of Possible Effects of the COVID-19 Pandemic on Febrile Neutropenia Episodes in Children With Acute Leukemia.

With the rapid spread of coronavirus disease 2019 (COVID-19) around the globe, concerns about the management of patients with malignancy have risen significantly. This study aimed to investigate the possible impact of the COVID-19 pandemic and prevention policies on the incidence and etiology of febrile neutropenia (FN) episodes in children with acute leukemia. Children who had acute leukemia and were diagnosed as FN in a tertiary center from March 2018 to March 2021 were included in the study. FN episodes were grouped as prepandemic and postpandemic based on the date that pandemic was declared. Relevant data were collected retrospectively. We evaluated 113 FN episodes (75.2% were prepandemic) of 46 patients, a median of 4.7 (2.6 to 12.6) years of age. The number of FN episodes per patient did not differ between prepandemic and postpandemic periods ( P =0.476). There was no significant difference among the 2 groups regarding the microbiologic causes, focus of fever, and clinical outcomes in FN episodes. Two of the patients were diagnosed as COVID-19 and recovered without any complications. In conclusion, we showed that the incidence and etiology of FN episodes were similar before and during the COVID-19 pandemic in children with acute leukemia.

Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey.

Assestment of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) is of utmost importance both for risk classification and tailoring of the therapy. The data of pediatric ALL patients that received treatment with Berlin-Frankfurt-Münster (BFM) protocols were retrospectively collected from 5 university hospitals in Turkey. Of the 1388 patients enrolled in the study 390 were treated according to MRD-based protocols. MRD assestment was with real time quantitative polymerase chain reaction (qPCR) in 283 patients and with multiparametric flow cytometry (MFC)-MRD in 107 patients. MRD monitoring had upstaged a total of 8 patients (2%) from intermediate risk group to high-risk group. Univariate analysis revealed age 10 years or above, prednisone poor response, PCR-MRD ≥10-3 on day 33 and on day 78 as poor prognostic factors affecting event-free survival (EFS). Detection of >10% blasts on day 15 with MFC (MFC-high-risk group) was not shown to affect EFS and/or overall survival (log-rank P=0.339). Multiple logistic regression analysis revealed PCR-MRD ≥10-3 on day 78 as the only poor prognostic factor affecting EFS (odds ratio: 8.03; 95% confidence interval: 2.5-25; P=0.000). It is very important to establish the infrastructure and ensure necessary standardization for both MRD methods for optimal management of children with ALL.

Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.

Pediatric trauma: Blood product transfusion characteristics in a pediatric emergency department, a single center experience.

AIM: To investigate clinical and laboratory data, management and outcomes of pediatric trauma patients who initially received blood product transfusions. METHODS: Between January 2011-January 2021, traumatic children who underwent blood product transfusions within 24 h of arrival at the emergency department were included. Demographics, clinical and laboratory data, Injury Severity Score (ISS), volume of transfused blood products and crystalloid boluses in 24 h were recorded. Massive transfusion (MT) was defined as transfusion of ≥40 mL/kg of all blood products in 24 h. RESULTS: Among 32 cases, 8 (25.0 %) patients met the MT threshold criterion. Length of pediatric intensive care unit (PICU) stay and mechanical ventilation (MV) were longer for patients who received MT although there was no difference for age, ISS, volume of crystalloid boluses, length of hospital stay, and 30-day mortality between those who received MT or not. Volume of crystalloid boluses was higher in patients who died than those who survived but the volume of blood products was similar for two groups. An APTT value of >37.5 s was identified as a predictor of 30-day mortality (OR = 48.000, 95 % CI: 3.704-621.998, p: 0.003). CONCLUSION: Children who received MT had longer durations of MV and PICU stay than those who did not receive, but there was no significance for ISS, volume of crystalloid boluses, hospital stay, or mortality between two groups. Volume of crystalloid boluses was higher in patients who died than those who survived. An APTT value of >37.5 s can be used to predict 30-day mortality.

Which Device Is Favorable for Intubation Attempts of Pediatric Residents on Four Different Pediatric Airway Simulations?

OBJECTIVES: Endotracheal intubation is an essential skill for the pediatric airway management. Although direct laryngoscopy (DL) is the standard method, several videolaryngoscopes (VLs) have been recently enhanced as an alternative especially for difficult intubations. We aimed to compare McGrath MAC (McG) and Storz C-MAC PM (ST) VLs with DL in terms of intubation success rate, time to intubation (TTI), and duration of obtaining glottis view of intubation attempts performed by pediatric residents on different pediatric airway manikins. METHODS: The pediatric residents with no experience in videolaryngoscopy were included. After a brief demonstration, intubation attempts with 3 randomly handled different devices with 6 different blades were performed on a child manikin, an infant manikin, a Pierre-Robin sequence infant manikin, and a child manikin with cervical immobilization sequentially. RESULTS: Fifty pediatric residents were enrolled. The attempts of DL on child manikin and attempts of all devices on child with cervical immobilization simulation were completely successful. For the attempts on both infant manikin and Pierre-Robin sequence infant manikin, the success rate of McG was significantly lower than ST and DL (P = 0.011 and P = 0.001). In the child manikin, McG and ST had prolonged TTI compared with DL (P = 0.016 and P = 0.001). For the child with cervical immobilization simulation, TTI of DL was significantly shorter than McG and ST (P = 0.011 and P = 0.001). Time to intubation of McG was significantly longer than DL and ST for the attempts on both 2 infant manikins. The rate of Cormack-Lehane grade I glottis view was similar for the attempts on both 2 child airway simulations. For infant manikin and Pierre-Robin sequence infant simulation, the rate of Cormack-Lehane grade I of ST was higher than attempts of DL and McG. CONCLUSIONS: The attempts of pediatric residents on infant normal airway and Pierre-Robin sequence infant airway simulations resulted with enhanced glottis view by the utilization of Storz C-MAC PM, but both 2 VLs did not provide the improvement of intubation success rate and TTI compared with DL on these 4 different pediatric manikins. Further clinical studies of different VLs in different clinical courses are required for a reliable utilization in children.

High-mobility Group Box 1 Protein in Pediatric Trauma Patients With Acute Traumatic Coagulopathy or Disseminated Intravascular Coagulation.

OBJECTIVES: Trauma can induce the release of high-mobility group box 1 (HMGB1), which plays an important role in the activation of coagulation. In this study, we aimed to evaluate the role of HMGB1 in the early diagnosis of acute traumatic coagulopathy (ATC), disseminated intravascular coagulation, and clinical course. MATERIALS AND METHODS: One hundred pediatric trauma patients and 50 healthy controls were enrolled. Demographic data, physical examination results, trauma scores, International Society on Thrombosis and Hemostasis score, laboratory values, transfusion requirements, and needs for mechanical ventilation were recorded. Blood samples for HMGB1 were assessed by an enzyme-linked immunosorbent assay. RESULTS: Thirty-five patients had ATC and 3 patients had overt disseminated intravascular coagulation. In trauma patients, HMGB1 levels were statistically higher than those in the control group (P<0.001). There was a positive correlation between HMGB1 levels and D-dimer levels (r=0.589, P<0.001). ATC patients had higher plasma HMGB1 levels than those without ATC (P=0.008). High HMGB1 levels were associated with the duration of mechanical ventilation, need for intensive care unit observation, length of hospital stay, and mortality. CONCLUSION: This study showed the early increase of HMGB1 in pediatric trauma cases and demonstrated the significant association of high HMGB1 levels with the development of ATC, disseminated intravascular coagulation, trauma severity, clinical outcome, and mortality.

Long-Term Follow-Up of a Case with Dyskeratosis Congenita Caused by NHP2-V126M/X154R Mutation: Genotype-Phenotype Association.

Dyskeratosis congenita (DC) is a rare inherited syndrome characterized by classical mucocutaneous features and the presence of other clinical features including bone marrow failure, pulmonary fibrosis, liver cirrhosis, and a predisposition to cancer. The symptoms develop at various ages and may manifest over time. Gene mutations associated with DC, such as DC1, TERC, TERT, TINF2, NHP2, NOP10, ACD, CTC1, NAF1, PARN, POT1, RTEL1, STN1, and WRAP53, have been identified in about 70% of patients. Since the number of patients with DC is small and the effect of genetic pathogenic variant may affect the phenotype, we wanted to present the clinical features and course of illness in a patient with NHP2 gene mutation (compound heterozygote for the NHP2 mutations c.376G>A/c.460T>A; amino acid substitutions: p.Val126Met and p.X154Arg) that occurred as a compound heterozygous state.

Cup-like Blasts in 2 Pediatric Patients With NPM-1-Positive Acute Myeloid Leukemia.

Cup-like phenotype is defined in some subtypes of acute myeloid leukemia (AML) and have been associated with NPM-1 and/or FLT3-ITD positivity in the presence of normal karyotype in >60% of patients. Herein we present two pediatric AML-M1 patients with cuplike nuclear morphology and NPM-1 positivity. Both patients were negative for FLT3-ITD mutation. NPM-1 mutation and FLT3-ITD mutation should be kept in mind in AML patients with cup-like blast morphology as these two mutations are important molecular markers for prognosis, risk group classification and also for response to treatment.

Induction Failure in Acute Leukemia or Parvovirus B19 Infection?

Parvovirus B19 infection may be seen in acute leukemia patients and clinical findings and cytopenia caused by the viral infection may complicate the evaluation of the remission status. Herein we present a standard risk pediatric acute lymphobiastic leukemia patient who developed myalgia, bone pain, bone marrow aplasia and sinusoidal obstruction syndrome at the end of the induction treatment and was diagnosed as having parvovirus B19 infection.

Neurotoxicity Associated With Dimethyl Sulfoxide Used in Allogeneic Stem Cell Transplantation.

Dimethyl sulfoxide (DMSO) is a cryoprotective agent used in storage of frozen stem cells in stem cell transplantation. Central nervous system side effects of DMSO such as epileptic seizures, stroke, transient global amnesia, and temporary leucoencephalopathy are rarely seen. Here, we report a pediatric patient who developed seizures after DMSO-cryopreserved stem cell infusion and whose magnetic resonance imaging of the brain demonstrated parietal and occipital focal cortical T2-signal intensity increase. DMSO toxicity should be kept in mind in patients who received cryopreserved stem cell infusion and magnetic resonance imaging may be helpful in differential diagnosis of central nervous system involvement.

Evaluation of the Clinical and Laboratory Characteristics of Previously Followed-up Thalassemia Intermedia Patients to Provide Them Better Care in the Future.

The increased awareness about the severity of complications in thalassemia intermedia patients led authorities to develop strategies for better management and follow-up of these patients. In this study, we aimed to define the clinical and laboratory characteristics in previously followed-up ß-thalassemia intermedia patients and wanted to gain an insight about the follow-up of this patient population in a developing country to provide them better care in the future. The mean age at diagnosis was 4 years, and the mean hemoglobin was 7.13 g/dL. The mean age at the beginning of regular transfusion was 4.8 years. An overall 74% of patients were on a regular transfusion program. The mean ferritin values at diagnosis and the last follow-up were 487 and 1225 ng/mL, respectively. The most common mutations detected in patients were IVS-I-110, IVS-I-6, IVS-II-1, and FCS 8/9 in order of frequency. Complications were seen in 48% of patients. The most common complications were osteopenia/osteoporosis (34%), growth retardation (24%), hypogonadism (18%), and cardiomyopathy (13%). In conclusion, the relatively higher complication rate in our patients who were previously treated highlights once again the need for an increased effort for optimal management and follow-up of this specific group of patients.