Cytokine release syndrome after CAR T-cell therapy for B-cell acute lymphoblastic leukemia in children and young adolescents: storms make trees take deeper roots.

INTRODUCTION: Chimeric antigen receptor (CAR) T-cells have revolutionized cancer treatment, showing significant success, including treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Despite their efficacy, cytokine release syndrome (CRS) emerges as a common early adverse effect that can be life threatening in severe cases, resulting from the immune system's targeted activation against tumors. AREAS COVERED: This review concentrates on CRS in children and young adults undergoing CAR T-cell therapy for B-ALL. It explores CRS pathophysiology, clinical presentation, and incidence, emphasizing the importance of a consensus definition and grading to homogenize the treatment according to the severity of symptoms. We will discuss the standard of care treatment of CRS but also novel approaches. We will highlight the importance of managing CRS without compromising the efficacy of immune cell activation against tumors. EXPERT OPINION: As CAR T-cell therapy in pediatric B-ALL become increasingly available and used, optimal management of CRS becomes increasingly important. Early recognition and timely management has improved. Further information will aid us to identify optimal timing of tocilizumab and corticosteroids. Continued bench research coupled with clinical studies and biomarker discovery will allow for valuable insights into CRS pathophysiology and patient and/or cell-targeted treatments.

Residual meta-iodobenzyl guanidine (MIBG) positivity following therapy for metastatic neuroblastoma: Patient characteristics, imaging, and outcome.

BACKGROUND: Meta-iodobenzylguanidine(MIBG) scans are used to detect neuroblastoma metastatic lesions at diagnosis and during posttreatment surveillance. MIBG positivity following induction chemotherapy correlates with poor outcome; however, there are reports of patients with progression-free survival despite MIBG positivity at the end of therapy. The factors distinguishing these survivors from patients who progress or relapse are unclear. FDG-positron-emission tomography (PET) scans can also detect metastatic lesions at diagnosis; however, their role in posttherapy surveillance is less well studied. METHODS: We performed a retrospective analysis of International Neuroblastoma Staging System (INSS) stage 4 patients to identify those with residual MIBG-avid metastatic lesions on end-of-therapy scans without prior progression. Data collected included age, disease sites, histopathology, biomarkers, treatment, imaging studies, and response. RESULTS: Eleven of 265 patients met inclusion criteria. At diagnosis three of 11 patients were classified as intermediate and eight of 11 high risk; nine of 11 had documented marrow involvement. Histologic classification was favorable for four of 10 and MYCN amplification was detected in zero of 11 cases. The median time with persistent MIBG positivity following treatment was 1.5 years. Seven patients had at least one PET scan with low or background activity. Biopsies of three of three MIBG-avid residual lesions showed differentiation. All patients remain alive with no disease progression at a median of 4.0 years since end of therapy. CONCLUSION: Persistently MIBG-avid metastatic lesions in subsets of patients following completion of therapy may not represent active disease that will progress. Further studies are needed to determine whether MYCN status or other biomarkers, and/or PET scans, may help identify patients with residual inactive MIBG lesions who require no further therapy.

Acute Severe Hyponatremia as a Serious Health Implication of Herbal Detox Regimens.

Hyponatremia is a serious health problem and can cause substantial morbidity and mortality as a result of osmotically induced cerebral edema if left untreated. Also, inappropriate rapid correction of chronic cases of hyponatremia can lead to osmotic demyelination with neurological impairment and death as consequences. It is defined as a serum sodium concentration less than 135 mmol/L. Herbal detox regimens are gaining popularity with their easy access over the counter and not well studied adverse effects. We hereby present a case of a 67-year-old man who developed severe hyponatremia after starting a five-day kidney detox regime. This regime consisted of drinking over a gallon (128 oz) of fluid daily, herbal tea with Uva Ursi leaves, juniper berries and several other ingredients. On the last day of this detox regime, he presented to the emergency department with a critical serum sodium level of 111 mmol/L associated with neurological symptoms. The purpose of this case report is to highlight the potential serious adverse effects associated with what is considered benign herbal medicine.

Association between paroxysmal tonic spasms and neuromyelitis optica.

OBJECTIVE: To determine the frequency of the association between tonic spasms and neuromyelitis optica (NMO) at our center. DESIGN: An institutional review board-approved retrospective study of clinical, serological, and radiographic characteristics of patients with NMO. SETTING: Multiple sclerosis center. PATIENTS: Patients with NMO treated at our center between 1990 and 2008. MAIN OUTCOME MEASURE: Records were examined for documentation of tonic spasms. RESULTS: Of 110 patients with International Classification of Diseases code 341, 57 patients met diagnostic criteria for NMO. Of these, 8 patients (14%) had documented typical tonic spasms (median age at onset, 39.5 years; range, 13.8-54.2 years). Of those patients, 4 were African American, 3 were Hispanic, and 1 was white. Only 1 was male. The NMO-IgG antibody was found in 1 of 6 patients tested. Tonic spasms appeared after a mean of 24.6 months (range, 0-91 months). In 2 of 57 patients meeting NMO criteria, tonic spasms accompanied their initial episodes. Seven of 8 patients who had tonic spasms responded to treatment with carbamazepine within 1 week. CONCLUSION: Tonic spasms are associated with NMO more commonly than with multiple sclerosis and may be a presenting sign in both diseases.

Diffuse large B-cell lymphoma presenting as Miller Fisher syndrome.

We report a patient with diffuse large B-cell lymphoma (DLBCL) who initially presented as Miller Fisher syndrome (MFS) responsive to high-dose immunoglobulin treatment. Detailed investigations for the recurrence of neurological symptoms revealed DLBCL that was responsive to chemotherapy. DLBCL should be considered in the differential diagnosis of patients with MFS who have worsening of their neurological condition after initial improvement with conventional therapy.

Impact of rituximab on relapse rate and disability in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is a severe demyelinating disease often leading to serious disability. Accumulating evidence now implicates humoral mechanisms in its pathogenesis. In the absence of an approved therapy, anti-inflammatory/immunosuppressant drugs have been used empirically for more than three decades. Recent evidence for a role of antibody to aquaporin-4 in the pathogenesis of NMO has led to the use of rituximab, a monoclonal antibody targeting the CD20 epitope on the entire B cell lineage. OBJECTIVES: To evaluate the impact of rituximab on the relapse rate and disability in NMO. METHODS: This is an IRB approved retrospective longitudinal study of NMO patients treated with rituximab. RESULTS: We identified 53 patients with NMO, 23 of whom had been treated with rituximab. These patients (2 males, 21 females) had a mean age of 37.1 ± 14.6 years at the time of diagnosis. Eight of the 23 treated with rituximab were treatment naïve. All 23 were scheduled to receive infusions every six or 12 months after treatment initiation with a minimum follow-up of six months (median 32.5 months, range 7-63 months). Median relapse rate declined significantly from 1.87 relapses/patient per year to 0.0 relapses/patient per year. Kurtzke Expanded Disability Status Scale (EDSS) scores stabilized or improved in all patients. Use of rituximab is associated with a significant reduction in relapses and disability in patents with NMO.

Spinal meningioma containing bone: a case report and review of literature.

Meningiomas constitute about 25% of primary spinal tumours and 1% to 5% of them are calcified. Ossification is a rare event and is rarely reported. Here, the case of a 40-year-old woman who had dorsal spinal cord meningioma (globular variety) at the T(6) vertebral level is reported; the meningioma showed a nidus of T2 weighting hypointensity on MRI as well as a bony chip inside the tumour intraoperatively. The tumour was successfully resected. Though the aetiology of ossification in the meningioma is not well known, metaplasia of arachnoid cells/dystrophic calcification may be the cause. Ossified meningiomas are more difficult to resect than the usual variety. Hypointensity inside tumour in T2-weighted images of MRI should make the surgeon suspicious of this condition, which may in some cases complicate tumour resection.