Long-term Outcomes Of Pediatric Patients Research Articles

Clinical characteristics and outcome of children with acute cryptorchid testicular torsion: A single-center, retrospective case series study

BackgroundCryptorchidism and testicular torsion (TT) are relatively common conditions in clinical practice; however, sparse information about cryptorchid TT is available in the current literature. MethodsWe retrospectively reviewed the clinical characteristics, treatment modalities, and long-term outcomes of pediatric patients treated for acute cryptorchid TT. ResultsWe found eight patients with unilateral acute cryptorchid TT with a prevalence of 8.9% (8/90) among all TT cases. The left testis was affected in six patients. The median age of patients at the time of the surgery was 65 months (interquartile range (IQR) 4–136 months). The median duration of symptoms was 16 h (IQR 9–25 h), while the median time to treatment was 60 min (IQR 59–63 min). The most common symptoms were pain (abdominal and inguinal) and inguinal mass with no palpable testis in the ipsilateral hemiscrotum. Preoperative color Doppler ultrasonography revealed absent or decreased testicular blood flow in the affected testes in 7/8 of patients. Various degrees of testicular torsion (median 540°, min 360°, max 1260°) were found during surgery. A necrotic testis that led to orchidectomy was found in 4/8 of patients. The median follow-up period was 42.6 months (IQR 12.5–71.2 months), revealing only one patient with testicular atrophy. The final testicular salvage rate was 35%. ConclusionsGreater awareness among caregivers and primary care physicians about acute cryptorchid TT is required to improve their timely diagnosis and treatment. A physical examination of the external genitalia and inguinal regions should be mandatory to attain a proper diagnosis and treatment without delay.

Very long-term outcomes of pediatric patients treated for optic pathway gliomas: A longitudinal cohort study.

Optic pathway gliomas (OPG) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications. We included patients treated at Gustave Roussy (GR) between 01.1980 and 12.2015 for OPG, before 18 years-old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and updated thanks to the GR long-term follow-up program and French national mortality registry for patients included in the French Childhood Cancer Survivor Study. We included 182 5y-OPG-childhood survivors in the analysis (sex-ratio M/F 0.8, 35% with NF1). With a median follow-up of 17.2y (range=5-41), we registered 82 relapses, 9 second malignancies and 15 deaths as first events after 5 years, resulting in 20-y conditional overall survival (C-OS) and late events-free survival (LEFS) of 79.9% (95%CI=71-86) and 43.5% (95%CI=36-51) respectively. NF1 (Hazard ratio HR=3, 95%CI=1.4-6.8), hypothalamic involvement (HR=3.2, 95%CI=1.4-7.3), and radiotherapy (HR=2.8, 95%CI=1.1-6.7) were significantly associated with C-OS in multivariable analyses. Ninety-five percent of 5y-OPG survivors suffered from any health condition, especially visual acuity "<1/10" (n=109), pituitary deficiency (n=106) and neurocognitive impairment (n=89). NF1 (HR 2.1) was associated with precocious puberty. With a median time post diagnosis of 4.2 years, 33 cerebrovascular events were observed in 21 patients. Late relapses, second malignancies and cerebrovascular diseases are severe late events resulting in premature mortality. Morbidity is high and needing after-cancer care to improve quality of life. Risk factors could be considered to better stratify long-term follow-up.

Retrospective, single-center analysis of autoimmune hepatitis in Jordanian children: clinical features, treatments, and outcomes

ObjectivesThis study describes clinical, biochemical, and histological features and long-term outcomes in pediatric patients diagnosed with autoimmune hepatitis (AIH) at King Abdullah University Hospital, Jordan.DesignRetrospective, single-center study.SettingKing Abdullah University Hospital, Jordan.ParticipantsInclusion of all pediatric patients with AIH diagnosed at our hospital from 2015 to 2023. Exclusion criteria was patients aged over 18 at time of diagnosis and those diagnosed elsewhere.Outcome measuresUnderstanding clinical, biochemical, and histological AIH features in children, evaluating treatment responses, and reporting short- and long-term complications, including mortality.ResultsSixteen pediatric cases were diagnosed, with an average age of 9.84 ± 4.13 years. Females comprised 75% of patients, and 31.3% presented with acute liver failure. Jaundice was the most common symptom, and hepatosplenomegaly was observed in 18% of cases. Most patients had elevated transaminase levels, along with positive anti-smooth muscle antibody (ASMA) and antinuclear antibodies (ANA). Common hematological abnormalities included anemia (56.3%) and thrombocytopenia (37.5%). All patients underwent liver biopsy, with interface hepatitis present in 81.3% of cases. Treatment mainly involved prednisone and azathioprine. Three patients died, one discontinued therapy, two patients were lost to follow-up, and 10 remained on treatment.ConclusionAutoimmune hepatitis affects Jordanian children, primarily female children. Jaundice is the most common presenting symptoms. Only Type I AIH occurred in our cohort. Although of good response to conventional treatment with steroids and immunosuppression, mortality reached 18.8%.

Outcomes of Portosystemic Shunts in Children with and without Liver Transplantation.

Limited data exist regarding outcome and morbidity associated with portosystemic shunts in the pediatric transplant population. Our study assesses the outcomes of pediatric patients who underwent a portosystemic shunt procedure, both with and without liver transplantation (LT). This study retrospectively reviewed the medical records of pediatric patients aged 0-19 years who underwent shunt placement between 2003 and 2017 at a tertiary care center. The analysis included cases of shunt placement with or without LT. A total of 13 pediatric patients were included in the study with median age of 8.8 years. Among the cases, 11 out of 13 (84.6%) underwent splenorenal shunt, 1 (7.7%) underwent a mesocaval shunt, and another 1 (7.7%) underwent a Modified Rex (mesoportal) shunt. Additionally, 5 out of 13 (38.5%) patients had LT, with 4 out of 5 (80.0%) receiving the transplant before shunt placement, and 1 out of 5 (20.0%) receiving it after shunt placement. Gastrointestinal bleeding resulting from portal hypertension was the indication in all cases. A total of 10 complications were reported in 5 patients; the most common complication was anemia in 3 (23.1%) patients. At the most recent follow-up visit, the shunts were functional without encephalopathy, and no deaths were reported. Shunt placement plays a crucial role in the management of patients with portal hypertension. Our study demonstrates favorable long-term outcomes in pediatric patients who underwent shunt placement. Long term shunt outcomes were similar and unremarkable in patients with LT and without LT.

Long-term outcomes of surgery for obstructive hypertrophic cardiomyopathy in a pediatric cohort

BackgroundSeptal reduction therapy via septal myectomy or a modified Konno procedure is the mainstay of therapy for drug-refractory obstructive hypertrophic cardiomyopathy (HCM), although outcomes data on septal myectomy in pediatric patients are limited. We evaluated long-term outcomes following surgery for obstructive HCM in a pediatric cohort. MethodsWe retrospectively reviewed patients age ≤18 years with obstructive HCM who underwent a left and/or right ventricular septal myectomy at our institution between 1992 and 2022. Primary endpoints were transplantation-free survival, freedom from HCM-related death, and cumulative probability of HCM-related reintervention. We further evaluated outcomes in patients with and without Noonan syndrome or other RASopathies. ResultsThirty-seven patients (median age, 7.4 years; interquartile range [IQR], 3.4-12.9 years) underwent transaortic septal myectomy. A combined modified Konno procedure was performed in 5 patients (13.9%). Sixteen patients (43.2%) had a RASopathy. A concomitant right ventricular outflow tract resection was performed in 9 patients (24.3%). There was 1 (2.7%) in-hospital death and 4 late deaths at a median follow-up of 10.5 years (IQR, 0.1-29.3). Twenty-year transplant-free survival and freedom from HCM-related death were 80.6% (95% confidence interval [CI], 64.2%-100%) and 87.1% (95% CI, 71.8%-100%), respectively. The 20-year cumulative probability of HCM-related reintervention was 34.2% (95% CI, 12.8%-57.1%). Seven patients required a septal reintervention. There was no difference in any primary endpoints between patients with and without a RASopathy. ConclusionsSurgery for obstructive HCM, including septal myectomy with and without a modified Konno procedure, may be performed with low morbidity and good long-term outcomes in pediatric patients. Recurrent outflow tract obstruction is not uncommon.

Does subtotal resection ameliorate hypothalamic morbidity in pediatric craniopharyngioma? A 30-year retrospective cohort study.

The optimal extent of resection of craniopharyngiomas to minimize the long-term risks of hypothalamic and endocrine dysfunction (obesity and panhypopituitarism) in children remains uncertain. The purpose of this study was to report long-term outcomes of pediatric patients with craniopharyngioma undergoing surgical treatment and to study rates of endocrinological and hypothalamic dysfunction in association with extent of resection. This retrospective study was performed in a cohort of children who underwent resection for craniopharyngioma at Children's of Alabama between 1990 and 2020. The primary outcome was hypothalamic dysfunction defined as a 0.5 increase in body mass index (BMI) Z-score and as a BMI > 2 SDs with or without psychiatric disturbances. Univariable analysis was performed using ANOVA, Wilcoxon rank-sum test, Pearson's chi-square test, and Fisher's exact test as appropriate. Missing data on the primary outcome were handled via multiple imputations. Relative risks were estimated using a multivariable generalized linear model with a priori variables selected using a modified Poisson regression approach with robust error variance to estimate risk ratios. The cohort includes 39 patients (24 girls and 15 boys; age range 1 month-16 years) who underwent resection of craniopharyngioma at the authors' center between 1990 and 2020. The preoperative goal of treatment was cyst decompression (CD) in 5, subtotal resection (STR) in 13, and gross-total resection (GTR) in 21 patients. The median long-term follow-up after surgery was 8.11 years (average 8.21, range 0.4-24.33 years). Univariate analysis demonstrated a statistically significant increase in hypothalamic dysfunction in patients undergoing GTR when compared to those undergoing STR or CD at 1 month postoperatively (p = 0.006) and 6-11 months postoperatively (p = 0.010), but with this difference not persisting beyond 1 year. Multivariable analysis showed patients older than 10 years at time of surgery to be the most affected and at highest risk of developing significant hypothalamic dysfunction. There was no significant difference in pituitary or neurological function between the STR/CD and GTR groups at 12-24 months or at most recent follow-up. There was no significant difference in BMI Z-scores between the STR/CD and GTR groups at 6-12 months or at most recent follow-up. Both STR and GTR of craniopharyngioma were associated with significant endocrinological sequelae after 1 year. These potential complications should be discussed with patients and their families, and postoperative protocols should include early nutritional and endocrinological interventions with endocrinologist consultation.

Pediatric Spinal Hemangioblastomas: Clinical Features and Surgical Outcomes of 39 Cases.

Spinal hemangioblastomas (HBs) are a rare pathology, especially in the pediatric population. The natural history and long-term outcomes of pediatric patients with spinal HBs remain unclear due to their scarcity. A retrospective review of the clinical data and treatment outcomes of children with spinal HBs in our institution from 2012 to 2021 was conducted. Thirty-nine pediatric patients were included, with an average age of 15.9 ± 2.9 years (range, 8-18 years), and 51.3% were female. Children were more likely to have von Hippel-Lindau (VHL) disease (p < 0.001), a family history of VHL (p < 0.001), multiple symptoms (p = 0.006), a shorter duration of symptoms (p < 0.001), and a larger lesion size (p = 0.004) and volume (p = 0.008) than their adult counterparts. The VHL-associated group of patients was more likely to present with multiple symptoms (p = 0.026), have a family history of VHL (p < 0.001), have multiple HBs (p < 0.001) and have synchronous intracranial lesions (p < 0.001) than the sporadic group. After surgery, 15 patients (38.5%) showed improved clinical outcomes, 17 patients (43.6%) remained unchanged, 4 patients (10.2%) worsened, and 3 patients (7.7%) died of tumor progression. During follow-up, there was a high rate of recurrence and repeated surgery, especially for children in the VHL-associated group. Pediatric patients with spinal HBs appear to have a higher relapse risk than their adult counterparts. Therefore, life-long follow-up of these patients is necessary, especially for VHL-associated cases. Surgery can benefit children with HBs and should be considered early to avoid irreversible neurological deterioration.

Pediatric Lyme disease: systematic assessment of post-treatment symptoms and quality of life.

Lyme disease is common among children and adolescents. Antibiotic treatment is effective, yet some patients report persistent symptoms following treatment, with or without functional impairment. This study characterized long-term outcome of pediatric patients with Lyme disease and evaluated the case definition of post-treatment Lyme disease (PTLD) syndrome. The sample included 102 children with confirmed Lyme disease diagnosed 6 months-10 years prior to enrollment (M = 2.0 years). Lyme diagnosis and treatment information was extracted from the electronic health record; parent report identified presence, duration, and impact of symptoms after treatment. Participants completed validated questionnaires assessing health-related quality of life, physical mobility, fatigue, pain, and cognitive impact. Most parents reported their child's symptoms resolved completely, although time to full resolution varied. Twenty-two parents (22%) indicated their child had at least one persistent symptom >6 months post-treatment, 13 without functional impairment (PTLD symptoms) and 9 with functional impairment (PTLD syndrome). Children with PTLD syndrome had lower parent-reported Physical Summary scores and greater likelihood of elevated fatigue. In the current study, most children with Lyme disease experienced full resolution of symptoms, including those who initially met PTLD syndrome criteria. Effective communication about recovery rates and common symptoms that may persist post-treatment is needed. The majority of pediatric patients treated for all stages of Lyme disease reported full resolution of symptoms within 6 months. 22% of pediatric patients reported one or more symptom persisting >6 months, 9% with and 13% without accompanying functional impairment. Effective communication with families about recovery rates and common symptoms that may persist post-treatment of Lyme disease is needed.

Aortic Injury From High-Speed Deceleration Against a Lap Belt in a 10-year-Old.

Traumatic aortic injuries in children and adolescents are rare, and even more rare are blunt traumatic injury to the abdominal aorta in this population. Therefore, there are few reports discussing the presentation and repair of such injuries, especially within the pediatric population. We report the successful repair of traumatic abdominal aortic transection in a 10-year-old female after a high speed MVC. She arrived in extremis with a seatbelt sign and was taken emergently for damage control laparotomy with subsequent postoperative CT findings of aortic transection/dissection at L3 with active extravasation. She immediately underwent open thrombectomy of the bilateral iliac arteries, and repair of her aortic injury with a 12 × 7mm Hemashield interposition graft extending just distal to the IMA and 1cm proximal to the aortic bifurcation. There are little data regarding long-term outcomes of pediatric patients undergoing different aortic repair techniques, and further research is needed.

Long-Term Outcome of Pediatric Patients with Anti-NMDA Receptor Encephalitis in a Single Center

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common autoimmune encephalitis in children. There is a high probability of recovery if treated promptly. We aimed to analyze the clinical features and long-term outcomes of pediatric patients with anti-NMDA receptor encephalitis. We conducted a retrospective study with definite diagnoses of anti-NMDA receptor encephalitis in 11 children treated in a tertiary referral center between March 2012 and March 2022. Clinical features, ancillary tests, treatment, and outcomes were reviewed. The median age at disease onset was 7.9 years. There were eight females (72.7%) and three males (27.3%). Three (27.3%) patients initially presented with focal and/or generalized seizures and eight (72.7%) with behavioral change. Seven patients (63.6%) revealed normal brain MRI scans. Seven (63.6%) had abnormal EEG results. Ten patients (90.1%) received intravenous immunoglobulin, corticosteroid, and/or plasmapheresis. After a median follow-up duration of 3.5 years, one patient was lost to follow-up at the acute stage, nine (90%) had an mRS ≤ 2, and only one had an mRS of 3. With the early recognition of anti-NMDA receptor encephalitis based on its clinical features and ancillary tests, we were able to treat patients promptly with first-line treatment and achieve favorable neurological outcomes.

Long-Term Outcomes of Pediatric Patients with Chordomas Treated with Proton Beam Radiation Therapy

<h3>Purpose/Objective(s)</h3> Chordomas are rare tumors that arise from embryonic remnants of the notochord and can arise anywhere along the spine or the base of skull. This condition is even more uncommon within the pediatric population, and standard of care treatment includes maximal safe resection with subsequent radiation. The use of proton radiation allows for a conformal delivery of radiation dose that potentially minimizes the exposure of sensitive nearby structures to harmful treatment effects. The purpose of this study is to evaluate the long-term survival and toxicity of pediatric patients with base of skull or cervical spine chordomas treated at this institution with proton-based radiation therapy. <h3>Materials/Methods</h3> This IRB-approved single-institution study examines a cohort of 36 pediatric patients (≤ 18 years old) with 39 lesions treated with proton radiation between 1994 and 2016. Patients were included if they were treated with definitive intent and had at least five years of time since completing radiation treatment. Median age at treatment of patients was 10.9 years old. 79% of lesions received subtotal resection, while 21% received gross total resection. 10 patients received chemotherapy. The vast majority of tumors was treated to 72-77.4Gy in 40-43 fractions. Two patients were treated to 66.6Gy in 37 fractions. <h3>Results</h3> Median follow-up time was 100 months. The 5-year overall survival for the entire cohort was 26/36 (72%), further stratified by gender to reveal 68% in the female cohort and 75% in the male cohort. Seven patients (19%) developed distant metastases and subsequent passed away from their disease. GTV over size of 25cc and poorly differentiated histology were associated with decreased overall survival and local control. Of the 30 patients with base of skull lesions, at most recent follow-up, 15 patients (50%) had ototoxicity with 12 of those cases related to adjuvant treatment. 17 patients had confirmed pituitary dysfunction or required pituitary hormone replacement at some timepoint after treatment, 7 patients had no dysfunction, 5 patients died without evidence of pituitary dysfunction, 1 patient did not have pituitary function tests available. No instances of brain or brainstem necrosis were seen. Of the 21 survivors, 20 were either in school or employed with no cognitive or learning disabilities present. <h3>Conclusion</h3> This single-institution experience shows the efficacy and safety of proton radiation in pediatric patients with chordomas. Limitations include small number of patients and retrospective nature of the study. Future directions include analysis at 10-year follow-up and further evaluation of long-term toxicity.

Clinical features and neurological outcomes in pediatric immune-mediated thrombotic thrombocytopenic purpura: A report from a large pediatric hematology center.

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and severely reduced or absent ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) activity, with varying degrees of organ dysfunction. As TTP is rare in pediatrics, most of the medical and scientific literature has largely reported on adult patients. As a result, limited data exist regarding the clinical features, comorbidities, treatment response, and long-term outcomes in pediatric patients with immune-mediated TTP. A single-center retrospective cohort study was conducted of all children and adolescents presenting to Children's Healthcare of Atlanta, Atlanta, Georgia, between the years 2001 and 2021 with immune-mediated TTP (iTTP). Clinical features, treatments, and outcomes, including long-term neurocognitive function, were analyzed. Eighteen individuals were identified, six of whom had a total of 10 relapses, amounting to 28 episodes overall. Thirty-eight percent of the patients experienced exacerbations but, ultimately, 85% achieved a clinical response and clinical remission. Only one in-hospital death occurred (mortality rate 5.5%). Seventy-three percent of analyzed patients demonstrated long-term neurocognitive abnormalities, including cognitive delay, learning difficulties, and severe depression. Children and adolescents recovering from iTTP are at high risk for neurocognitive deficits from initial and possibly ongoing microvascular disease. Due to risk for long-term neurological deficits, we recommend neuropsychological testing in addition to monitoring of other organ functions in all children with TTP, as well as long-term surveillance of ADAMTS13 activity during remission to detect and promptly treat early relapse.

Clinical Characteristics of Pediatric Patients with Urea Cycle Disorders

Objective: Urea cycle disorders (UCDs) are inherited deficiencies of the enzymes or transport molecules involved in the cellular excretion of excess ammonia produced during protein metabolism. The aim of this study was to evaluate the clinical characteristics and long-term outcome of pediatric patients with UCDs. Material and Methods: Our research was conducted between September 2020-March 2021 in Dr. Sami Ulus Maternity and Child Health Training and Research Hospital. Clinical characteristics in 16 patients with UCDs [carbamoyl phosphate synthetase I deficiency (n=1), N-acetylglutamate synthase deficiency(n=1), argininosuccinate lyase deficiency (n=4), argininosuccinate synthetase deficiency (n=4), arginase deficiency (n=2), ornithine transcarbamylase deficiency (n=2), hyperammonemia hyperornithinemia homocitrullinuria syndrome (n=2)] were defined. The term “neonatal-onset” UCD was used if symptoms occurred within 28 days of life, and “late-onset” if symptoms started after the neonatal period. Results: Eight patients presented with acute metabolic crisis during newborn period. Core clinical phenotype in neonatal-onset UCDs included sepsis-like findings, whereas epilepsy and mental retardation was predominant in lateonset UCDs. For patients with neonatal-onset UCDs, hyperammonemia was more severe at the initial period. Conclusion: Despite evolving treatment opportunities, still high mortality rates were found in neonatal-onset UCD. UCDs should be suspected in pediatric patients with hyperammonemia and metabolic investigations should be performed immediately to enlighten diagnosis. Neonatal-onset UCD usually present with symptoms of acute hyperammonemia, while moresubtle neurological manifestations are frequent initial findings in the late onset UCD.

Sacral-Alar-Iliac (SAI) Fixation in Children With Spine Deformity: Minimum 10-Year Follow-Up.

Sacral-alar-iliac (SAI) screws are utilized to achieve pelvic fixation in spine deformity patients. The primary purpose of this study is to investigate the long-term outcomes of pediatric patients with scoliosis treated with posterior spinal fusion and SAI fixation at 10-year clinical and radiographic follow-up. We reviewed the clinical and radiographic records of patients aged 18 years or below treated for scoliosis with posterior spinal fusion using SAI fixation. Pelvic obliquity and the major coronal curve were determined at the preoperative visit and 6-week, 1-year, 5-year, and 10-year postoperative visits. SAI screw-specific data collected included screw dimensions, rate of screw revision, pain at the SAI screw sites, presence of lucency >2 mm around the screw, screw loosening or breaking, and deep surgical site infections. Ninety-seven of 151 patients (75%) were included. The average age at index surgery was 13.5±3.1 years, and the most common diagnosis was cerebral palsy (67%). The mean duration of follow-up was 11±3 years. The mean pelvic obliquity measured 20±8.0 degrees preoperatively, and 8.7±4.0 degrees at the 10-year follow-up. There were no significant difference in pelvic obliquity when comparing the 10-year follow-up visit with the 6-week postoperative follow-up. Average screw dimensions were 8.4×68.8 mm. By the 10-year follow-up, 4 patients (4%) had at least 1 SAI screw-related complication. Of these patients, 2 (2%) had pain at 1 SAI screw, 4 (4%) had lucency around the screw, and 3 (3%) had broken or loose screws. Two (2%) required SAI screw revision because of late deep wound infection, and underwent exchange with a longer screw. There were no intrapelvic protrusions, vascular, or neurological complications. SAI screws are a safe and effective method for pelvic fixation in children with spinal deformity. The outcomes at ≥10 years are satisfactory, with low rates of long-term complications and excellent postoperative correction and subsequent maintenance of coronal curvature and pelvic obliquity over time. Level IV.

Long-term Outcomes of Pediatric Tracheostomy Home Care in a Limited Resource Setting of Professional Home Nurse

Long-term outcomes of pediatric patients with a tracheostomy in developing countries where professional home nurse is not accessible has rarely been reported. We, therefore, investigated the prevalence and associating factors of long-term outcomes in these children. Retrospective chart review was conducted in 85 tracheostomized children who were discharged to home during January 2012 to December 2020. Tracheostomy home care was provided by caregivers who completed the tracheostomy home care program. Prevalence of unplanned readmission with acute respiratory problems within 30 days after the first hospital discharge was 17.6%. Lower respiratory tract infection (LRTI) after hospital discharge was found in 72.9% (median frequency of 1.0 episode/case/year). Among 80 children who had surveillance airway endoscopy, 46.3% demonstrated late tracheostomy-related airway complications. Independent factor associated with late tracheostomy-related airway complications was a follow-up period longer than 1 year. Decannulation success was found in 21.2%. Most of them had tracheostomy for their upper airway anomalies. The mortality rate was 7%. Most of them died from their underlying diseases. In conclusion, pediatric tracheostomy home care undertaken by caregivers is feasible in developing countries where home nurse is not available. The prevalence of unplanned readmission with acute respiratory problems within 30 days after hospital discharge and late tracheostomy-related airway complications were comparable with those reported in developed countries. However, we still had a high prevalence of post-tracheostomy LRTI which was a challenging problem that needed to be investigated and resolved.

128 - CD45RA-Depleted Haploidentical Transplantation Combined with NK Cell Addback Results in Promising Long-Term Outcomes in Pediatric Patients with High-Risk Hematologic Malignancies

128 - CD45RA-Depleted Haploidentical Transplantation Combined with NK Cell Addback Results in Promising Long-Term Outcomes in Pediatric Patients with High-Risk Hematologic Malignancies

Impact of Time to Diagnosis on Morbidity and Survival in Children With Malignant Central Nervous System Tumors.

The aim was to determine the impact of time to diagnosis (TTD) on morbidity and mortality and to identify factors associated with overall survival (OS) in pediatric patients with malignant central nervous system (CNS) tumors. This is a retrospective review of all malignant CNS tumors presenting to 2 tertiary care pediatric hospitals from 2000 to 2019. Cox proportional hazard model analysis outcomes included TTD and OS as well as morbidity; stratified by tumor category, age, relapse, and presence of metastatic disease. There were 197 children with malignant CNS tumors (mean age 8.7 y, 61% male). Tumors included medulloblastoma (N=58, 29.4%), ependymoma (N=27, 13.7%), high-grade glioma (N=42, 21.3%), germ cell tumors (N=47, 23.9%), and other embryonal tumors (N=23, 11.7%). Median TTD from symptom onset was 62 (interquartile range: 26.5 to 237.5 d) and 28% had metastatic disease. Three-year progression free survival was 55% and 3-year OS was 73.1%. Increased OS was associated with increased TTD (parameter estimate 0.12; confidence interval [CI]: 0.019-7.06; P =0.019), high-grade glioma (hazard ratio [HR]: 2.46; CI [1.03-5.86]; P =0.042), other embryonal tumor (HR: 2.84; CI [1.06-7.56]; P =0.037), relapse (HR: 10.14; CI: 4.52-22.70; P <0.001) and metastatic disease (HR: 3.25; CI: 1.51-6.96; P =0.002). Vision change (HR: 0.58; CI: 0.313-1.06; P =0.078), hearing loss (HR: 0.71; CI: 0.35-1.42; P =0.355), and cognitive impairment (HR: 0.73; CI: 0.45-1.19; P =0.205) were not associated with TTD in this model. Increased median TTD is associated with higher OS in pediatric patients treated for malignant CNS tumors. Tumor biology and treatment modality are more important factors than TTD for predicting morbidity and long-term outcomes in pediatric patients with CNS tumors.

Long-term outcomes in pediatric patients who underwent living donor liver transplantation for biliary atresia

BackgroundThere is no consensus about long-term outcomes in patients with biliary atresia. We retrospectively reviewed the long-term outcomes in pediatric patients who underwent living donor liver transplantation for biliary atresia. MethodsBetween May 2001 and December 2020, 221 (73%) of 302 pediatric patients who underwent living donor liver transplantation had biliary atresia. The median age at living donor liver transplantation was 1.2 (range 0.2–16.5) years, and follow-up was 10.3 ± 5.5 years. ResultsThe 10-year graft survival rates in patients with and without biliary atresia were 94% and 89%, respectively (P = .019). The 10-year graft survival was significantly poorer in patients ≥12 years of age (84%) versus those <12 years of age at living donor liver transplantation (0–2 years: 95%; 2–12 years: 96%) (P = .016). The causes of graft failure in patients with biliary atresia included late-onset refractory rejection (n = 6), bowel perforation (n = 2), and acute encephalitis (n = 2), as well as cerebral hemorrhage, hepatic vein thrombosis, and sepsis (n = 1 for all). All 7 patients with graft failure due to refractory rejection and hepatic vein thrombosis underwent repeated liver transplantation and are alive in 2021. The rates of post-transplant portal vein complications and early-onset acute cellular rejection in patients with biliary atresia were higher than in those without biliary atresia (P = .042 and P = .022, respectively). In 2021, of 60 adolescents with biliary atresia, 14 (23%) reported medication nonadherence. The rate of liver dysfunction due to late-onset acute cellular rejection and graft failure due to late-onset refractory rejection in patients with nonadherence was higher than in patients with satisfactory adherence (P = .009). ConclusionThe long-term prognosis after living donor liver transplantation in pediatric patients with biliary atresia is quite good. However, long-term support to enhance medication adherence is required in adolescents with biliary atresia.

CD45RA-Depleted Haploidentical Transplantation Combined with NK Cell Addback Results in Promising Long-Term Outcomes in Pediatric Patients with High-Risk Hematologic Malignancies

Novel graft engineering strategies that allow selective T-cell depletion have made haploidentical donor (haplo) hematopoietic cell transplantation (HCT) feasible for patients lacking a matched donor. We hypothesized that selective CD45RA+ cell depletion can limit graft-versus-host disease (GVHD) through removal of naive T cells but allow for rapid immune reconstitution through adoptive transfer of memory T cells, minimizing risk of graft failure, infections and relapse. We performed a prospective clinical trial utilizing CD45RA+ depleted haplo HCT followed by donor NK cell addback to maximize the graft-versus-leukemia effect in children with high-risk hematological malignancies (NCT01807611), and present here an interim analysis.Between 2013 to 2019, 72 patients (42 males, 30 females) were enrolled. The median age was 8.1 years (range 0.6-20.8). Twenty-nine patients had acute lymphoblastic leukemia (ALL), 39 had myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), 3 had biphenotypic leukemia and 1 had Non-Hodgkin's Lymphoma. At time of HCT, 25 patients were in CR1, 24 in CR2, 4 in CR3/> and 19 had active disease. Of the 53 patients in CR, 22 had evidence of minimal residual/detectable disease (MRD) at HCT. Donors used were mothers (n=30), fathers (n=35), or sibling/other (n=6) with majority (n=62) being KIR-ligand mismatched to the recipient. All patients received serotherapy-free, reduced intensity conditioning with fludarabine, melphalan, cyclophosphamide and Total Lymphoid Irradiation. GCSF mobilized peripheral blood grafts were infused on i) Day 0 CD34 + selected graft (median CD34+: 9.85 x10 6cells/kg, range 1.96-44.64) and ii) Day +1 CD45 RA+ depleted graft (median: CD34+: 5.82 x10 6cells/kg, range 0.58-39.43); providing a large number of CD45RO+ T-cells (median CD3+ : 60.1 x10 6cells/kg, range 16.08-528.43) after depletion of CD45RA+ cells (CD3+CD45RA+ median 0, range 0-0.2 x10 6cells/kg). NK cells (median: 11.7 x10 6cells/kg; range: 1.65-99.2), isolated from a non-mobilized apheresis by CD3 depletion/CD56 selection, were infused on day +6. GVHD prophylaxis included MMF (n=61) and/or Sirolimus (n= 8) until day +42 post-HCT.The median time for neutrophil and platelet engraftment was 11 (range 9-13) and 17 days (range 10-100) respectively. One patient had primary graft failure and was successfully re-transplanted. Immune reconstitution was rapid and robust and recapitulated CD45RA depleted graft content with mean CD3, CD4 and CD8 T-cell count at day +30 of 1080, 640 and 230 cells/ul respectively. TCR Vbeta spectratyping revealed a broad repertoire by day +100 prior to the emergence of naïve T cells. The incidence of Cytomegalovirus and Adenovirus viremia was 38% (28/72) and 13% (10/72) respectively. The cumulative incidence of aGVHD was 36.1% (25.1-47.2%), aGVHD grade III-IV was 29.2% (19.1-39.9%) and chronic GVHD was 20.8% (CI: 12.3-30.9%). With a median follow-up of 3.1 years (range 0.04-8.0 years) the 3-year leukemia free survival (LFS) was 88% (CI: 76.1-100%) for patients in CR1, 70.8% (CI: 54.8-91.6%) for patients in CR2, 50% (CI: 18.8-100%) for patients in CR3/> and 21.1% (CI: 8.81-50.3) for patients with active disease (p = <0.0001). Amongst patients in CR, those with no detectible disease had 3-year LFS of 84.4% (CI: 72.7-97.9%) as compared to 68.2% (CI: 51.3-90.7%) for patients with detectible MRD at time of HCT (p=0.087). Three-year LFS was comparable for ALL and AML at 62.1% (CI 46.7-82.5%) and 58.5% (CI 44.8-76.4%) respectively (p=0.95). For the entire cohort, the 3-year OS and LFS was 68.9% and 62.2% (CI 58.9-80.6% and 51.9-74.6%), respectively. Despite the inclusion of patients with active disease and detectible MRD the cumulative incidence of relapse for the entire cohort was 26.5% (CI:16.8-37.1%), comparable to other studies with patients transplanted in MRD-negative CR. The cumulative incidence of non-relapse mortality was 11.5%, (CI, 5.3-20.4%), with 5/10 deaths occurring in the 19 patients with active disease.In conclusion, selective CD45RA+ depletion allowed for adoptive transfer of abundant memory T cells that along with NK cell addback was associated with rapid, functional immune reconstitution, resulting in low rates of graft failure, viral reactivation and relapse. Despite a higher incidence of aGVHD compared to other T-cell depleted grafts, our approach translated into promising long-term outcomes in this high-risk patient population. DisclosuresSharma: Vindico Medical Education: Honoraria; CRISPR Therapeutics: Other, Research Funding; Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Novartis: Other: Salary support paid to institution; Spotlight Therapeutics: Consultancy; Medexus Inc: Consultancy. Gottschalk: Novartis: Consultancy; Catamaran Bio: Consultancy; Other: Other: patents and patent applications in the field of cancer cell and gene therapy ; Immatics: Membership on an entity's Board of Directors or advisory committees; Tidal: Consultancy; Tessa Therapeutics: Consultancy. Triplett: Miltenyi: Other: Travel, meeting registration.

Mucosal healing is not associated with better outcome during 7 years of follow-up in pediatric patients with Crohn's disease.

Mucosal healing (MH) has become a perspective treatment target in patients with Crohn's disease (CD). Data about the impact of MH on long-term outcome in pediatric patients are still scarce. 76 pediatric patients with CD were evaluated retrospectively (2000-2015) in a tertiary care center. Based on MH achievement, they were divided into two groups (MH, n= 17; and No MH, n=59). The primary endpoint was to assess the association of MH and the need for CD-related hospitalizations or surgery in pediatric patients with CD. The number of hospitalized patients was 24% in the MH group and 42% in the No MH group, P = 0.26. The total number of CD-related hospitalizations was not significant between the MH group and the No MH group (5 vs. 41, P = 0.15). The time to the first hospitalization was 24 months in MH and 21 months in No MH, P>0.99. 24% patients in the MH group and 39% patients in the No MH group underwent CD-related operation, P = 0.39. Time to the first operation was 43 months for MH and 19 months for the No MH group, P = 0.13. The follow-up period was 91 months in the MH group and 80 months in the No MH group, P = 0.74. The use of infliximab was positively associated with MH, P = 0.002. MH was not associated with fewer CD-related hospitalizations or operations in pediatric patients with CD during seven years of follow-up.