Long-term Survival In Pediatric Patients Research Articles

Durable Engraftment and Excellent Overall Survival After CD34-Selected Peripheral Blood Stem Cell Boost in Pediatric Patients With Poor Graft Function Following Allogeneic Stem Cell Transplantation

Poor graft function (PGF) is a life-threatening complication after allogeneic stem cell transplantation (alloSCT). Historically, outcomes of patients with PGF have been very poor, and there are no standardized approaches to treatment. Furthermore, few outcomes after CD34-selected stem cell boost (CD34+SCB) for PGF in pediatric alloSCT recipients have been reported. Here we report on a single center experience with CD34+SCB for PGF after alloSCT in patients treated on the Pediatric Transplant and Cellular Therapy Service at MSK Kids, Memorial Sloan Kettering Cancer Center. A retrospective analysis of patients transplanted for malignant and nonmalignant disorders who received a CD34+SCB between 2008 to 2020 for treatment of PGF defined as the need for granulocyte colony-stimulating factor (G-CSF) and/or packed red blood cell or platelet transfusion support with bone marrow donor chimerism ≥85%. Peripheral blood stem cells from the original donor were the source for CD34+SCB. Durable complete recovery (durable CR) was defined as recovery of peripheral blood counts without recurrent need for G-CSF or transfusion support. The main outcomes of interest were recovery of hematopoiesis and overall survival. Development of graft versus host disease (GVHD) was an additional outcome of interest. Fourteen patients with PGF received a boost. Six patients had no known infection, while 8 patients had PGF associated with an infection. The probability of CR at 60 days was 79% (95% confidence interval [CI], 57%-100%). The overall survival at both 2 and 5 years was 78% (95% CI, 56%-100%). One patient developed GVHD, which was fatal. No other CD34+SCB-related toxicities were observed. While including patients with PGF as recently defined by the American Society for Transplantation and Cellular Therapy, as well as PGF in patients with concomitant infections, we demonstrate that CD34+SCB is safe and can provide for durable trilineage hematopoietic recovery and long-term survival in pediatric patients after alloSCT.

Acute coronary syndrome in an 8-year-old child with familial hypercholesterolemia: a case report

BackgroundFamilial hypercholesterolemia (FH) is the most commonly inherited metabolic disease and has an autosomal dominant mode of inheritance. Patients with FH usually present with high levels of low-density lipoprotein-cholesterol, xanthomas and early coronary artery disease. Children with FH are subject to developing early and enhanced atherosclerosis, leading to an increased risk of coronary events. We report here an 8-year-old patient with acute coronary syndrome (ACS) who was diagnosed with homozygous FH (HoFH) due to mutations in the low-density lipoprotein receptor (LDLR) gene and subsequently treated with percutaneous transluminal coronary angioplasty (PTCA) after filtration plasma. To the best of our knowledge, this patient is the youngest case of HoFH treated with filtration plasma followed by PTCA reported to date.Case presentationAn 8-year-old Asian patient was admitted to Gansu Provincial Hospital presenting symptoms of ACS. Laboratory tests showed that the patient’s cholesterol and low-density lipid levels were extremely high. An electrocardiogram (ECG) revealed sinus arrhythmia and electric axis deviation to the right, but the ECG was roughly normal. Multiple cardiac function abnormalities were diagnosed on the ECG. Multiple sites of coronary artery stenosis were determined by computed tomography angiography. DNA sequencing of exons showed a C-to-A substitution at nucleotide 126 in exon 2, resulting in a LDLR mutation in the patient and seven other family members. Following combination treatment with lipid-lowering drugs, anti-thrombosis drugs, filtration plasma and PTCA, the patient’s symptoms were significantly improved and the patient discharged.ConclusionWe report the rare case of a patient with ACS attributable to HoFH who was treated with PTCA following filtration plasma. The patient was shown to have clinically diagnosed and molecularly confirmed HoFH that resulted from a mutation in the LDLR gene. Children with HoFH have higher risk of early coronary events and death from myocardial infarction due to premature atherosclerosis than adults. Earlier intervention and treatment will bring great benefits to the long-term survival of pediatric patients.

Three decades' analysis of pediatric liver transplantation outcomes reveals limited long-term improvements.

The aim of this study was to assess improvements in long-term survival of pediatric patients after liver transplantation by analyzing outcomes in transplant recipients who survived beyond 1year after transplantation. There has been a marked increase in the 1-year survival of pediatric patients, from 78% in transplant recipients between 1987 and 1990 to 95% in transplant recipients between 2011 and 2017. The long-term outcomes have not seen a similar trend, creating a disparity that warrants analysis. We analyzed 13753 pediatric patients who survived for 1year after receiving orthotopic liver transplantation between 1987 and 2017. The study period was divided into six eras. Outcomes were analyzed using the Kaplan-Meier method for time-to-event analysis, and multivariable Cox regression. There were no significant gains in long-term outcomes among 1-year survivors over the past three decades. Log-rank tests for equality of survivor functions between each era and 1987-1990 were not statistically significant. Cause of death analysis revealed that although infections caused 20.6% of deaths in patients transplanted between 1987 and 1990, this number dropped to 5.6% in those transplanted between 2011 and 2017 (p=.01). Malignancy caused 10.6% of deaths in 1987-1990 but caused 22.2% of the deaths in 2011-2017 (p=.04). Despite the gratifying gains in short-term survival of pediatric patients, 1-year survivors have no significant improvements in long-term survival after undergoing a liver transplantation. Long-term sequelae of immunosuppression, such as malignancy and infection, continue to be the most common causes of death. This study highlights the necessity for better long-term management of immunosuppression.

Minimal residual disease surveillance at day 90 predicts long-term survival in pediatric patients with T-cell acute lymphoblastic leukemia

To evaluate the optimal time to monitor minimal residual disease (MRD) for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL). Children newly diagnosed with T-ALL were treated per the CCLG-ALL2008 protocol in our hospital. MRD was monitored at days 15, 33 and 90, and the patients were stratified as low-, intermediate- or high-risk according to MRD at days 33 and 90. The 5-year event-free survival (EFS) and overall survival (OS) rates for all patients were 60.1 ± 5.6% and 63.1 ± 5.6%, respectively. The median follow-up time was 54 (0.3–120) months. Univariate analysis showed that the 5-year EFS rate correlated with MRD at days 33 and 90 (p < .01). Multivariate analysis demonstrated that only MRD at day 90 and involvement of the central nervous system (CNS) were independent prognostic factors. MRD at day 90 likely provides better prognostic value for pediatric T-ALL patients. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00707083

Assessment and Management of Platinum-Related Ototoxicity in Children Treated for Cancer.

Platinum compounds are a group of chemotherapeutic agents included in many pediatric and adult oncologic treatment protocols. The main platinum compounds are cisplatin, carboplatin, and oxaliplatin. Their use in clinical practice has greatly improved long-term survival of pediatric patients, but they also cause some toxic effects: ototoxicity, myelosuppression, nephrotoxicity, and neurotoxicity. Hearing damage is one of the main toxic effects of platinum compounds, and it derives from the degeneration of hair cells of the ear, which, not having self-renewal capacity, cannot reconstitute themselves. Hearing loss from platinum exposure is typically bilateral, sensorineural, and permanent, and it is caused by the same mechanisms with which platinum acts on neoplastic cells. According to available data from the literature, the optimal timing for the audiological test during and after treatment with platinum compounds is not well defined. Moreover, no substances capable of preventing the onset of hearing loss have been identified.

Radiation Therapy for Optic Pathway and Hypothalamic Low-Grade Gliomas in Children

The long-term survival of pediatric patients with optic pathway or hypothalamic low-grade glioma (LGG) who receive radiation therapy (RT) has not been previously assessed. A retrospective study was performed of all patients with optic-hypothalamic pediatric LGG treated with RT at a single institution. Eligible patients were aged ≤21years at the time of RT and had localized LGG diagnosed by neuroimaging or histology. The median RT dose was 54Gy, delivered in 30 fractions. Event-free survival (EFS) was defined as survival without progression or secondary high-grade glioma. Days were counted from the first day of RT. Eighty-nine patients were included in the study, with a median follow-up period of 12.5years. Of the patients, 14 had neurofibromatosis type 1 (NF-1). The 10-year EFS rate was 61.9% (95% confidence interval [CI], 31.2%-82.1%) for patients with NF-1 and 67.5% (95% CI, 54.8%-77.3%) for those without NF-1. The 10-year overall survival rate was 92.3% (95% CI, 56.6%-98.9%) for patients with NF-1 and 98.4% (95% CI, 89.1%-99.8%) for those without NF-1. Pre-RT chemotherapy (which was more commonly given to younger patients) was associated with reduced EFS, whereas younger age was associated with reduced overall survival. Possible RT-induced neoplasms developed in 8 patients, including 4 with NF-1. The 10-year cumulative incidence of clinically significant vasculopathy was 7.1% (95% CI, 2.9%-13.9%); vasculopathy did not develop in any child aged >10years at the commencement of RT. RT is an effective treatment for optic-hypothalamic LGG. Older children without NF-1 have a low risk of late toxicity. RT can be considered for selected younger patients or individuals with NF-1 as a salvage treatment after progression.

Long-Term Outcomes Following Pediatric Out-of-Hospital Cardiac Arrest*

Pediatric out-of-hospital cardiac arrest is an uncommon event with measurable short-term survival to hospital discharge. For those who survive to hospital discharge, little is known regarding duration of survival. We sought to evaluate the arrest circumstances and long-term survival of pediatric patients who experienced an out-of-hospital cardiac arrest and survived to hospital discharge. Retrospective cohort study King County, WA Emergency Medical Service Catchment and Quaternary Care Children's Hospital Persons less than 19 years old who had an out-of-hospital cardiac arrest and were discharged alive from the hospital between 1976 and 2007. None. During the study period, 1,683 persons less than 19 years old were treated for pediatric out-of-hospital cardiac arrest in the study community, with 91 patients surviving to hospital discharge. Of these 91 survivors, 20 (22%) subsequently died during 1449 person-years of follow-up. Survival following hospital discharge was 92% at 1 year, 86% at 5 years, and 77% at 20 years. Compared to those who subsequently died, long-term survivors were more likely at the time of discharge to be older (mean age, 8 vs 1 yr), had a witnessed arrest (83% vs 56%), presented with a shockable rhythm (40% vs 10%), and had a favorable Pediatric Cerebral Performance Category of 1 or 2 (67% vs 0%). In this population-based cohort study evaluating the long-term outcome of pediatric survivors of out-of-hospital cardiac arrest, we observed that long-term survival was generally favorable. Age, arrest characteristics, and functional status at hospital discharge were associated with prognosis. These findings support efforts to improve pediatric resuscitation, stabilization, and convalescent care.

Impact of Kidney Function on Long-Term Survival in Pediatric Patients with End-Stage Heart Failure Undergoing Heart Transplantation: An Analysis of the United Network of Organ Sharing Database

Impact of Kidney Function on Long-Term Survival in Pediatric Patients with End-Stage Heart Failure Undergoing Heart Transplantation: An Analysis of the United Network of Organ Sharing Database

Long-Term Outcome of Pediatric Patients with Severe Aplastic Anemia Treated with Antithymocyte Globulin and Cyclosporine

To determine the long-term outcomes in children with severe aplastic anemia (SAA) treated with antithymocyte globulin (ATG) and cyclosporine (CsA) through a retrospective analysis of the pediatric patients treated at our institution in all protocols that included horse ATG (h-ATG) and CsA. Between 1989 and 2006, a total of 406 patients, 20% of whom were children under age 18 years, received an initial course of immunosuppressive therapy (IST) at our institution. Here we report the outcome of 77 children who were treated with an h-ATG plus CsA-based regimen during this period. The overall response rate at 6 months was 74% (57/77); the cumulative incidence of relapse at 10 years was 33%, and the median time to relapse was 558 days. The cumulative incidence of evolution after IST was 8.5%; all 3 such events occurred in partial responders. Overall, there were 13 deaths (17%), with 4 occurring within the 3 months after IST in patients who had a pretreatment absolute neutrophil count of < 100/microL and the other 9 occurring more than 6 months after initiation of IST. The median time to death was 570 days. The overall 10-year survival for the entire cohort was 80%; long-term survival in the children who responded to IST was 89%. The long-term survival in pediatric patients who respond to IST is excellent, at about 90%. IST remains a good alternative in pediatric patients who lack an HLA-matched sibling donor and should be offered as initial therapy before possible hematopoietic stem cell transplantation from an unrelated donor.

Surgical management of pediatric Cushing's disease

Background Cushing's disease may have a direct effect on growth pattern, pubertal maturation, and long-term survival in pediatric patients. Methods Dexamethasone suppression test was done in 10 children (median age, 15 years) and showed variable suppressibility, with microadenoma seen in 5, macroadenoma in 3, and normal gland in 2 patients. Inferior petrosal sinus sampling (IPPS) was also carried out and confirmed pituitary adenoma as source of ACTH in 2 patients. We adopted sublabial transsphenoidal (n = 9) or pterional transylvian route (n = 1) in macroadenoma with conchal sphenoid sinus. Serum cortisol level <50 nmol/L was taken as the criteria for biochemical remission. Results Clinical remission was achieved in 7 of 10 operated patients. In 2 patients where clinical remission was achieved, postoperative BSC could not be done. Postoperative BSC was less than 50 nmol/L in 2 (25%) of 8 patients and remained elevated in 6. Remission was achieved in both patients with postoperative BSC less than 50 nmol/L and in 3 of 6 with elevated levels. Three patients had neither clinical nor biochemical remission: 2 underwent bilateral adrenalectomy and 1 received radiotherapy. Postoperative CSF leak seen even in microadenomas associated with arachnoidal prolapse. Among 7 patients who initially remitted (median follow-up of 82 months; range, 24-120 months), recurrence of disease occurred in 3 (42.8%) patients after a median interval of 5 years. Conclusions In children with CD, endocrinal manifestations are more frequent than visual symptoms. Transsphenoidal route is the preferred approach, but a nonpneumatised sphenoid sinus may be present. Sellar arachnoidal prolapse may cause postoperative CSF leak even in microadenomas. Surgery is the first line of treatment, but constant monitoring is mandatory to pick up the relapsed cases.

The natural history of hepatitis C virus in pediatric liver transplant recipients

Although rare in the pediatric population, the natural history of hepatitis C virus (HCV) recurrence in pediatric patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease secondary to HCV has not been well described. We performed an analysis of all 67 pediatric patients (< 17 years old) who have undergone OLT for HCV in the United States between 1/1988 and 6/2005. The 67 pediatric patients received a total of 83 OLTs for HCV. Following initial OLTs performed for HCV, the patient and allograft survival rates were 71.6% and 55.0%, respectively, at 5 years. Following retransplantation these rates decreased to 55.0% and 33.8%, respectively, following retransplantation. Recipients were listed for retransplantation after 31.3% of all OLTs, and overall recipients were retransplanted after 19.3% of OLTs. The overwhelming majority of retransplants were performed for HCV recurrence. A mean of 1.2 OLTs were performed per patient for HCV. The median time between OLTs for HCV was 290 days. In conclusion, the risk of HCV recurrence in pediatric OLT recipients is high and is associated with a high rate of retransplantation. Still, OLT represents the only treatment option that may achieve long-term survival in pediatric patients with end-stage liver disease secondary to HCV that is recalcitrant to medical management.

Treatment of CML in pediatric patients: should imatinib mesylate (STI-571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy?

Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes.

Treatment-related esophageal stricture in pediatric patients with cancer

Intensive antineoplastic regimens have enhanced long-term survival in pediatric patients with cancer, but can result in long-term complications. Esophageal stricture formation is one such complication. We reviewed the experience with benign esophageal stricture in pediatric patients with cancer over the past 15 years in a major cancer center. Clinical course, along with endoscopic, radiologic, and manometric esophageal studies, was reviewed. Esophageal strictures formed in five pediatric patients who were treated with radiation and/or chemotherapy. Stricture formation was associated with abnormal esophageal motility in four out of the five patients. Repeated esophageal dilation was performed from 3-50 times and resulted in stricture resolution in only 2 of the 5 patients. Esophageal stricture formation in this population is rare, but is associated with long-term morbidity.