Hepatosplenic γδ T‐cell lymphoma of two adolescents: Case report and retrospective literature review in children,adolescents, and young adults

HSTCL is a highly aggressive malignancy with a poor prognosis. Case series and accounts have reported the use of different chemotherapy regimens with diverse patient outcomes. Most long‐term survivors had undergone high‐dose chemotherapy with autologous or allogeneic HCT. We describe two pediatric patients with HSTCL who were treated with chemotherapy followed by allogeneic HCT. Both patients are alive and in complete remission 2 and 8 years after therapy. Multiagent chemotherapy followed with allogeneic HCT seems to provide patients who have chemotherapy‐sensitive disease a long‐term disease‐free survival.     

Long‐term outcomes of pediatric kidney transplant recipients with a pretransplant malignancy

A childhood malignancy can rarely progress to ESRD requiring a KT. To date, few reports describe long‐term outcomes of pediatric KT recipients with a pretransplant malignancy. Between 1963 and 2015, 884 pediatric (age: 0‐17 years old) recipients received 1055 KTs at our institution. KT outcomes were analyzed in children with a pretransplant malignancy. We identified 14 patients who had a pretransplant malignancy prior to KT; the majority were <10 years old at the time of KT. Ten (71%) patients received their grafts from living donors, the majority of which were related to the recipient. Wilms' tumor was the dominant type of pretransplant malignancy, seen in 50% of patients. The other pretransplant malignancy types were EBV‐positive lymphoproliferative disorders, non‐EBV‐positive lymphoma, leukemia, neuroblastoma, soft‐tissue sarcoma, and ovarian cancer. Ten of the 14 patients received chemotherapy as part of their pretransplant malignancy treatment. Graft survival at 1, 3, and 5 years was 93%, 83%, and 72%, respectively. Patient survival at 1, 5, and 10 years was 100%, 91%, and 83%, respectively. Six (40%) patients suffered AR following KT; half of them had their first episode of AR within 1 month of KT. Our single‐center experience demonstrates that pediatric KT recipients with a previously treated pretransplant malignancy did not exhibit worse outcomes than other pediatric KT patients.     

Clinical management of hereditary angio‐oedema in children

Hereditary angio‐oedema (HAE) results from the deficiency of C1‐esterase inhibitor (C1‐INH). The clinical picture of this autosomal dominant disorder is characterized by recurrent attacks of subcutaneous oedema and/or potentially life‐threatening swelling of the submucosa. This review discusses the authors' decade‐long experience obtained in the treatment and follow‐up of pediatric patients with HAE. Twenty‐six children with HAE were reviewed. Pedigree analysis was performed in all cases to identify afflicted relatives. C1‐INH concentrate was reserved for the emergency treatment of acute oedematous attacks, whereas tranexamic acid and danazol were administered for short‐ or long‐term prophylaxis. Follow‐up care included laboratory tests and abdominal ultrasound, which was repeated at regular intervals. Twenty‐one children had Type I HAE and five suffered from Type II HAE. Clinical manifestations of the disease first occured in children when 2.5–12 years of age. Oedema formation primarily afflicted subcutaneous tissues. Mechanical trauma was identified as a precipitating factor in 20 patients. Pedigree analysis revealed 24 patients with relatives who suffered from HAE. Long‐term prophylaxis with tranexamic acid or danazol was initiated in 11 patients; two children required short‐term prophylaxis. No drug‐related adverse effects were observed, except for one case of delayed menarche. Therapy improved serum complement parameters significantly and substantially reduced the frequency and severity of clinical episodes. Adequate prophylaxis and follow‐up care can spare pediatric patients from oedematous attacks caused by HAE. Undesirable adverse effects can be avoided and the patient's quality of life enhanced considerably by administering the lowest effective drug dose.     

Hematopoietic stem cell transplantation in children with Griscelli syndrome: A single‐center experience

GS2 is a rare autosomal recessive disease characterized by hypopigmentation, variable immunodeficiency with HLH. HSCT is the only curative treatment for GS2. We analyzed the outcome of 10 children with GS2 who underwent HSCT at our center between October 1997 and September 2013. The median age of the patients at transplant was 13.5 months (range, 6‐58 months). All of the patients developed HLH before HSCT and received HLH 94 or HLH 2004 protocols. Donors were HLA‐identical relatives in 8 patients, HLA‐mismatched relatives in 2 patients. Engraftment was achieved in all except one patient. None of the patients developed acute GVHD. Chronic GVHD occurred in one and veno‐occlusive disease occurred in four patients. Eight of the patients are under remission without any neurologic sequelae—median time of disease‐free survival is 92.4 months. The present study shows successful transplant outcome without long‐term neurologic sequelae in patients with GS2 who underwent HSCT from HLA‐related donors.     

Bronchiectasis following treatment for high‐risk neuroblastoma: A case series

High‐risk (HR) neuroblastoma remains a very challenging disease to treat and long‐term cure is only possible with intensive, multimodal treatment including chemotherapy, high‐dose therapy, radiotherapy, surgery, and immunotherapy. As a result, treatment‐related morbidity and late effects are common in survivors. This report outlines a case series of six patients who developed a chronic productive cough following treatment for HR neuroblastoma. High‐resolution computed tomography scanning confirmed the diagnosis of bronchiectasis. Two of the patients who have undergone immunological testing demonstrate hypogammaglobulinaemia and impaired vaccine response. Persistent cough in patients treated for neuroblastoma warrants investigation and consideration of immunological referral.     

Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma

There is no established salvage regimen for pediatric patients with relapsed nasopharyngeal carcinoma (NPC) and outcomes are dismal. We performed a multicenter retrospective review to determine outcomes after first salvage therapy for pediatric patients with relapsed NPC. Fourteen patients were treated with varied regimens. Two of the 14 patients received oxaliplatin‐containing regimens and achieved a long‐term complete response. Although definitive recommendations cannot be made based on outcomes for 14 patients who received varied regimens, we discuss justification for an oxaliplatin‐containing regimen in combination with gemcitabine as a reasonable choice for first‐line salvage therapy for pediatric patients with relapsed NPC.     

Pediatric liver transplantation for neonatal‐onset Niemann‐Pick disease type C: Japanese multicenter experience

Niemann‐Pick disease type C (NPC) is a rare autosomal recessive inherited disease characterized by lysosomal accumulation of free cholesterol in macrophages within multiple organs. Infantile‐onset NPC often presents with jaundice and hepatosplenomegaly from birth, but these symptoms usually improve during early childhood, and it rarely progresses to liver failure. We report three cases from different hospitals in Japan; the patients developed neonatal‐onset NPC, and liver transplantation (LT) was performed as a life‐saving procedure. LT was performed at 19 days, 59 days, and 4 months of age, respectively. The last patient was diagnosed with NPC before LT, while the first two patients were diagnosed with neonatal hemochromatosis at LT. In these two patients, the diagnosis of NPC was made more than a year after LT. Even though oral administration of miglustat was started soon after the diagnosis of NPC, all patients showed neurological regression and required artificial respiratory support. All patients survived more than one year after LT; however, one patient died due to tracheal hemorrhage at 4.5 years of age, and another one patient was suspected as recurrence of NPC in liver graft. In conclusion, while LT may be a temporary life‐saving measure in patients with neonatal‐onset NPC leading to liver failure, the outcome is poor especially due to neurological symptoms. A preoperative diagnosis is thus critical.     

Newborn hypocarnitinemia due to long‐term transplacental pivalic acid passage

Infants often develop hypocarnitinemia and resultant hypoglycemia during long‐term treatment with antibiotics that contain pivalic acid, but it is unknown whether maternal treatment with such agents during pregnancy induces hypocarnitinemia in fetuses or neonates. A woman at week 28 of pregnancy was prescribed cefcapene pivoxil for 84 consecutive days for treatment and prophylaxis of pyelonephritis. Using tandem mass spectrometry, both the mother and newborn were found to have hypocarnitinemia soon after delivery. It was concluded that the baby suffered from secondary hypocarnitinemia due to long‐term prenatal treatment with antibiotics containing pivalic acid. Long‐term treatment with antibiotics containing pivalic acid in pregnant women can induce hypocarnitinemia in both the mother and neonate; reported herein is the first case observed in humans.     

Living‐donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow‐up

Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long‐term (17 years post‐LT) and short‐term (9 months post‐LT) follow‐up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long‐term clinical outcomes.     

Henoch–Schönlein purpura in children

Henoch–Schönlein purpura is the most common systemic vasculitis of childhood. In the majority of children, the outcome of Henoch–Schönlein purpura is excellent with spontaneous resolution of symptoms and signs. However, a small subset of patients will develop long‐term sequelae in the form of chronic kidney disease. While the clinical presentation and diagnosis of Henoch–Schönlein purpura is straightforward, treatment of Henoch–Schönlein purpura nephritis and long‐term renal outcomes of more severely affected children are less certain. This review article gives a general overview of Henoch–Schönlein purpura with emphasis on recently published information, including the new classification of childhood vasculitis, insights into pathogenesis of Henoch–Schönlein purpura and a summary of various treatments of established Henoch–Schönlein purpura nephritis.     

Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long‐term management with anti‐inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti‐inflammatory treatment of AD. Pimecrolimus 1% is approved for second‐line use in children (≥2 yr old) and adults with mild‐to‐moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long‐term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short‐ and long‐term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long‐term intermittent use. Unlike topical corticosteroids, long‐term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post‐marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.     

Outcomes of two‐drug maintenance immunosuppression for pediatric renal transplantation: 10‐yr follow‐up in a single center

Minimizing IS to reduce side effects without compromising long‐term renal transplant survival is the goal of all IS protocols. We conducted a retrospective study of pediatric renal transplants performed August 1988 to July 2008 and treated with two‐drug maintenance therapy by one of three protocols: prednisone/cyclosporine without induction (SB) or with daclizumab induction (SBI), or tacrolimus/mycophenolate with daclizumab induction (SF). Kaplan–Meier survival curves were used to determine graft and patient survival at one, three, five, and 10 yr. Associations between graft survival and patient/transplant characteristics were determined using log‐rank test and CPH model adjusting for treatment group. About 208 patients were included in the analysis (96 SB, 97 SBI, 15 SF; 148 DD, 60 LD, 37 pre‐emptive). Overall graft and patient survival at one, three, five, and 10 yr were similar to the previously published results of pediatric renal transplants in similar years treated predominantly with three‐drug maintenance therapy ( https://web.emmes.com/study/ped/annlrept/2010 ). Only biopsy‐proven TG was significantly associated with worse graft survival (HR 11.5, 95% CI: 3.4, 38.7). Malignancy rate was low (2.4%) with little PTLD (0.5%). Few opportunistic or other infections occurred (<5% patients). Minimizing IS to a two‐drug maintenance regimen had no adverse effect on long‐term transplant outcome and had low malignancy and infection rates.     

Cognitive behavioral treatment for childhood anxiety disorders: long‐term effects on anxiety and secondary disorders in young adulthood

Background: The present study’s aim was to examine the long‐term effects (8 to 13 years post‐treatment; M = 9.83 years; SD = 1.71) of the most widely used treatment approaches of exposure‐based cognitive behavioral treatment for phobic and anxiety disorders in children and adolescents (i.e., group treatment and two variants of individual treatment). An additional aim was to compare the relative long‐term efficacy of the treatment approaches. Method: At long‐term follow‐up, participants (N = 67) were between 16 and 26 years of age (M = 19.43 years, SD = 3.02). Primary outcome was the targeted anxiety disorder and targeted symptoms. Secondary outcomes were other disorders and symptoms not directly targeted in the treatments including (1) other anxiety disorders and symptoms, (2) depressive disorders and symptoms, and (3) substance use disorders and symptoms. Results: Long‐term remission for anxiety disorders and symptoms targeted in the treatments was evident 8 to 13 years post‐treatment. Long‐term remission also was found for the secondary outcomes. There were more similarities than differences in the long‐term gains when comparing the treatment approaches. Conclusions: Consistent with past research, the study’s findings provide further evidence that the short‐term benefits of exposure‐based CBT for childhood phobic and anxiety disorders using both group and individual treatment may extend into the critical transition years of young adulthood.     

Individualized long‐term enzyme therapy for Gaucher disease type 1 in Slovenia

Background: Gaucher disease type 1 (GD1) was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed. We describe the management of eight GD1 patients in Slovenia who were diagnosed between the ages of 2 and 15 years. Methods: Patients were individually assessed to establish initial enzyme doses and monitored frequently to determine the effects of long‐term enzyme dose regimens. Outcomes up to 10 years after long‐term treatment are described by changes in the Zimran severity score index, chitotriosidase and acid phosphatase levels, and after 2001, bone parameters (DEXA bone mineral density scores and the MRI bone marrow burden score). Results: Following the initiation of enzyme therapy with individualized dose regimens (range 25–56 U/kg/14 days) and followed by a gradual reduction of doses (range 12–35 U/kg/14 days) during long‐term maintenance, disease status improved in all patients as measured by the Zimran severity score index (from a mean of 11.25 [median 11.5] before therapy to a mean of 4.12 [median 3.5] at last report). Anemia and leucopenia resolved in all patients, chitotriosidase and acid phosphatase levels decreased in all patients (and by over 75% in six patients) within 1 year of treatment. Bone marrow burden scores improved in all monitored patients and DXA scores improved in six of seven monitored patients. Conclusions: We conclude that enzyme therapy with relatively low, individualized dose regimens is well‐tolerated and effective in children and young adults with GD1 disease, who are regularly monitored for changes in disease status.     

The role of allogeneic hematopoietic stem cell transplantation and Epstein‐Barr virus infection on the treatment for child primary hemophagocytic lymphohistiocytosis patients with X‐linked lymphoproliferative disease: A rare case report and family survey study

XLP‐2 is known as a rare primary immunodeficiency disease, which is characterized by the susceptibility to EBV infection and potential development into the pHLH. The existing studies believe that the dysfunction of XIAP represents one of the most significant pathogenic mechanisms of XLP‐2, and allo‐HSCT is regarded as a crucial treatment for the long‐term survival in XLP‐2 patients. In our present study, a 2‐year‐old male patient was diagnosed with XLP‐2. After receiving chemotherapy by using HLH‐2004 without allo‐HSCT, he reached a complete remission, and his EBV load was brought under control. Our family survey revealed a novel frameshift mutation in the XIAP gene in this patient, as well as in his cousin and grandfather. Until now, the patient has been followed up for 22 months with no recurrence reported yet. Based on these findings, it is believed that for child pHLH patients with XLP‐2, the treatment by controlling symptoms alone without allo‐HSCT and with regular monitoring of EBV load could be conducive to a long‐term survival.     

Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the commonest soft tissue sarcoma (STS) in children. Most cases occur in young children and although the majority are sporadic, RMS can be a manifestation of certain cancer predisposition syndromes. Treatment for RMS involves a multimodality approach including chemotherapy, surgery and radiotherapy with attendant risks of long term treatment related morbidities. Whilst outcomes in localised RMS have improved steadily, those for metastatic and relapsed disease remain poor and there is a pressing need for novel therapeutic approaches. This review outlines the key points related to the diagnosis and management of children with RMS with a focus on current and future practice within the UK and Europe.     

Standard of Care for Neuropsychological Monitoring in Pediatric Neuro‐Oncology: Lessons From the Children's Oncology Group (COG)

As the mortality of pediatric cancers has decreased, focus on neuropsychological morbidities of treatment sequelae have increased. Neuropsychological evaluations are essential diagnostic tools that assess cognitive functioning and neurobiological integrity. These tests provide vital information to support ongoing medical care, documenting cognitive morbidity and response to interventions. We frame standards for neuropsychological monitoring of pediatric patients with CNS malignancy or who received cancer‐directed therapies involving the CNS and discuss billing for these services in the United States in the context of clinical research. We describe a cost‐effective, efficient model of neuropsychological monitoring that may increases access to neuropsychological care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.     

Pediatric kidney transplantation in Egypt: Results of 10‐year single‐center experience

Pediatric kidney transplantation is a multidisciplinary therapy that needs special consideration and experience. In this study, we aimed to present CUCH experience; over a 10‐year period, as a specialized center of kidney transplantation in children. We studied 148 transplantations performed at a single center from 2009 to 2018. Pretransplant and follow‐up data were collected and graft/patient survival rates were evaluated. A total of 48 patients developed at least one rejection episode during 688 patient‐years of follow‐up. Infections, recurrence of original disease, and malignancy were the most important encountered medical complications (20%, 2%, and 1.4%, respectively). One‐year patient survival was 94.1%, while graft and patient survival was 91.9%. Graft/patient survival at 5, 7, and 9 years was 90%, 77%, and 58%, respectively. Infections were the main cause (69%) of mortality. Death with a functioning graft and CR were the main causes of graft loss (48% and 33%, respectively). Pediatric kidney transplantation in Egypt is still a challenging yet successful experience. Rejections and infections are the most frequent complications. Short‐term outcomes surpass long‐term ones and graft survival rates are similar to the international standard.     

Stable long‐term renal function after pediatric liver transplantation

Herlenius G, Hansson S, Krantz M, Olausson M, Kullberg‐Lindh C, Friman S. Stable long‐term renal function after pediatric liver transplantation.
Pediatr Transplantation 2010: 14:409–416. © 2010 John Wiley & Sons A/S. Abstract: Long‐term exposure to calcineurin inhibitors increases the risk of CKD in children after LT. The aims of this study were to study renal function by measuring GFRm before and yearly after LT, to describe the prevalence of CKD (stage III: GFR 30–60 mL/min/1.73 m²) and to investigate if age and underlying liver disease had an impact on long‐term renal function. Thirty‐six patients with a median age of 2.9 years (0.1–16 yr) were studied. Median follow‐up was 6.5 (2–14 yr). GFRm decreased significantly during the first six months post‐transplantation with 23% (p < 0.001). Thereafter renal function stabilized. At six months, 17% (n = 5) of the children presented CKD stage III and at five yr the prevalence of CKD III was 18% in 29 children. However, in 13 children with a 10‐year follow‐up it was 0%. None of the children required renal replacement therapy after LT. When analyzing renal function of those children younger than two yr (n = 14) and older than two yr (n = 17) at the time of transplantation, we found that in both cohorts the filtration rate remained remarkably stable during the five‐yr observational period. However, there was a statistically significant (p < 0.05) difference in the percentual decrease in GFRm between the groups during the first six months after LT 13% and 31%, respectively. Baseline GFRm according to diagnosis did not differ between the groups. During the first six months after LT, patients transplanted for hepatic malignancy (n = 6) and those with metabolic liver disease (n = 4) had a percentage loss of GFRm of 32% and 35%, respectively. The corresponding loss of GFRm in patients with other diseases was 10‐19%. Six months post‐transplantation mean GFRm in the group with malignant liver disease was 65 ± 15 mL/min/1.73 m² and in the group with other diseases (n = 24) 82 ± 17 mL/min/1.73 m² (p < 0.05). At one, three and five yr post‐transplantation there was no longer a statistically significant difference between these cohorts. Our findings suggest that there can be a long‐term recovery of renal function after LT in children.     

Surveillance imaging for high‐grade childhood brain tumors: What to do 10 years after completion of treatment?

Brain tumors are the second most common childhood cancer. Treatment protocols for high‐grade pediatric brain tumors recommend regular follow‐up imaging for up to 10 years. We review maximal time to recurrence and minimal time to radiologically detectable long‐term sequelae such as secondary malignancies, vascular complications, and white matter disease. No tumors recurred after the 10‐year point, but radiological long‐term sequelae grew more common as the treatment completion date receded. We do not recommend regular imaging more than 10 years after treatment has ended, unless there are clinical symptoms.