A comprehensive strategy to address shortage of Erwinia asparaginase in pediatric acute lymphoblastic leukemia.

BACKGROUND: Pegylated form of E. coli derived asparaginase (PEG) is a crucial component of pediatric ALL therapy. Patients who develop a hypersensitivity (HSR) reaction with PEG receive an alternative form - Erwinia asparaginase (EA). However, an international shortage in 2017 had made it challenging to treat these patients. We have developed a comprehensive strategy to address this need. PATIENTS AND METHODS: This is a single center, retrospective analysis. All patients receiving PEG were premedicated to reduce infusion reactions. Patients who developed HSR underwent PEG desensitization. Patients were compared to historic controls. RESULTS: Fifty-six patients were treated within the study period. There was no difference in the frequency of reactions before and after the adoption of universal premedication (p = 0.78). Eight patients (14.2%) developed either ≥ Grade 2 HSR or silent inactivation and 5 patients (62.5%) successfully underwent desensitization. The remaining three patients received EA asparaginase. This intervention led to a decrease in PEG substitution, with 3 patients (5.3%) requiring EA compared to 8 patients (15.09%) in the pre-intervention period. (p = 0.11) PEG desensitization was more cost effective than EA administration. CONCLUSION: PEG desensitization is a safe, cost effective, and practical alternative in children with ALL and a Grade 2 or higher HSR.

Esophageal carcinoma in children and adolescents.

BACKGROUND: Esophageal cancer is rare in children and is limited to isolated case reports. We describe 2 cases of esophageal carcinoma (1 case each of squamous cell carcinoma and adenocarcinoma) and present literature review of esophageal carcinoma in childhood. OBSERVATIONS: Both of our patients had common symptoms of progressive dysphagia and significant weight loss at presentation. We were unable to identify any specific predisposing factors for either adenocarcinoma (caustic ingestion, reflux disease, Barrett esophagus) or squamous cell carcinoma (caustic ingestion, inherited bone marrow failure syndromes). Both patients responded poorly to chemotherapy and died of progressive disease. CONCLUSIONS: On account of the rarity of esophageal carcinoma in this age group, there are no management guidelines for the pediatric oncologist. There is a strong need for collaborative efforts between adult and pediatric oncologists to establish cooperative diagnostic and therapeutic protocols for successful management of rare pediatric tumors like esophageal carcinoma.

Iatrogenic spinal epidermoid cyst after lumbar puncture using needles with stylet.

Iatrogenic spinal epidermoid tumors are extremely rare and may be caused by implanted skin fragments in the spinal canal, most commonly due to lumbar punctures using hollow needles without a stylet. The authors report for the first time an iatrogenic spinal epidermoid tumor that developed 26 months after several lumbar punctures, performed using disposable spinal needles with stylet, in an 8-year-old boy with persistent lower back pain. The authors hypothesize that an ill-fitting stylet compounded by multiple therapeutic lumbar punctures and young age as possible risk factors for the development of the tumor in the present case. A total excision of the tumor with laminectomy yielded good symptomatic recovery.

Epiphyseal Primary Diffuse Large B-Cell Lymphoma of Bone.

Primary lymphoma of bone (PLB) confined to the epiphysis has only been described in four other patients. Due to the rarity of this entity, diagnosis has often been delayed, leading to mismanagement with adverse clinical consequences. We report a fifth case of primary epiphyseal lymphoma of bone located in the left distal medial femoral epiphysis of a 13-year-old boy. Radiographic and histologic features of PLB are discussed, along with a review of the literature and pitfalls of misdiagnosis. The patient initially presented with six months of progressive left knee pain with an associated loss of passive range of motion. Imaging revealed a mixed radiolucent lesion within the left distal medial femoral epiphysis with cortical breakthrough. A core biopsy was performed revealing a blue round cell tumor. Thanks to modern immunohistochemistry techniques, a diagnosis of primary lymphoma of bone was quickly made. The patient thus avoided further surgical intervention and received the appropriate treatment of chemotherapy, with subsequent rapid resolution of the lesion. This case highlights the necessity of including primary lymphoma of bone in all epiphyseal lesion differential diagnoses, especially in the pediatric patient population when aggressive radiographic features are present.

Varicella in a Previously Immune Patient With Leukemia.

Infection with varicella-zoster virus (VZV) in oncology patients can result in severe disease with an increased risk of morbidity and mortality [1, 2]. Among patients on cancer chemotherapy, only nonimmune persons are considered to be susceptible to varicella [1]. We present a case of varicella in a child with leukemia that occurred despite immunity as defined by 2 doses of varicella vaccine and documentation of positive VZV immunoglobulin G titer before initiation of chemotherapy.

Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens.

OBJECTIVE: To determine the prevalence, duration, and a potential cause of humoral defect(s) in children with acute lymphoblastic leukemia (ALL) at least 1 year after completion of chemotherapy. STUDY DESIGN: Antibody titers for mumps, rubeola, rubella, tetanus and diphtheria toxoid, poliovirus serotypes 1, 2,and 3, Haemophilus influenzae type b, varicella, and hepatitis B were obtained from 100 children with ALL. Children with non-protective titers to these microbial antigens were re-vaccinated and re-studied after anamnestic vaccine challenge. RESULTS: The percent of children with ALL who had protective titers was markedly less than that anticipated for immunized control subjects. Longitudinally, many titers fluctuate between protective and non-protective antibody responses after re-immunization. The chemotherapy protocol used did not affect the ability of these children to express protective antibody responses. T-, B-, and NK-cell numbers and proliferative responses to mitogens were all normal. Age correlated with titer results for certain vaccines. CONCLUSIONS: Children in remission from ALL have a high prevalence of humoral immune defects that are not related to any specific chemotherapy regimen. This antibody deficiency may place children with ALL at risk for the development of these bacterial and viral diseases, even after completion of chemotherapy. Pediatricians, oncologists, or both should periodically monitor humoral immunity after chemotherapy and re-vaccinate these children, as needed, to ensure prolonged immunoprotection.