Unusual Presentation of T-cell Large Granular Lymphocytic Leukemia.

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder that can arise from T- or natural killer-cell lineages. It is an indolent disease that typically occurs in the sixth decade of life. Most cases of T-cell LGL leukemia (T-LGL) are associated with autoimmune disorders. Patients with T-LGL are generally asymptomatic; however, they can present with symptoms related to neutropenia, infections, and autoimmune disorders. Here, we report two cases of T-LGL in which the patients presented with liver dysfunction.

Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia. METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared. RESULTS: A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p < 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068). CONCLUSIONS: In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia.

Pembrolizumab in Combination with Chemotherapy in Patients with ERBB2-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (ERBB2) mutation is a known oncogenic driver mutation in a small proportion of non-small cell lung cancers (NSCLCs). Many targeted therapies are being developed and investigated for the treatment of ERBB2-mutated NSCLC, however none of these agents have yet been approved as a front-line treatment. Thus, platinum-based chemotherapy with or without immunotherapy remains the preferred first-line therapy for ERBB2-mutated NSCLC. OBJECTIVE: We aimed to study the activity of chemotherapy in combination with pembrolizumab as first-line treatment in patients with stage IV ERBB2-mutated NSCLC. PATIENTS AND METHODS: We retrospectively identified five patients with ERBB2-mutated NSCLC treated with carboplatin, pemetrexed and pembrolizumab as first-line therapy between 2018 and 2020. Overall survival (OS), progression-free survival (PFS), and time to next therapy (TTNT) were summarized by Kaplan-Meier methodology using R 4.0.5 with median time to event. Response rates defined by partial response (PR) or PR + stable disease (SD) and 95% Clopper-Pearson confidence interval (CI) were calculated. RESULTS: The median age of these five patients was 60 years and all five patients' tumors had ERBB2 mutations-4 had exon 20 mutation and 1 had exon 23 mutation. With a median follow-up of 32 months, the median OS was 24 months, the median PFS was 9 months, and the median TTNT was 9 months. The response rate was 0.6 for PR (Clopper-Pearson exact 95% CI 0.147-0.947) and 0.8 for PR and SD (Clopper-Pearson exact 95% CI 0.284-0.995). No unexpected toxicities were observed. CONCLUSION: In a small number of patients, chemotherapy and pembrolizumab as first-line therapy in ERBB2-mutated NSCLC patients demonstrated activity similar to previous reports with this regimen. Future clinical trials are needed to determine the role of chemotherapy and immunotherapy for this patient population in the context of emerging targeted agents.

A Case of Symptomatic Cerebral Radiation Necrosis for an Extra-Cranial Neoplasm from Conventional Radiotherapy With Concurrent Immunotherapy.

Cerebral radiation necrosis (RN) is a known complication of brain radiotherapy (RT). The incidence rate of RN varies with the total dose, dose fractionation, and radiotherapy modality. Concurrent treatment with immunotherapy can increase the risk factors for developing RN through a synergistic mechanism. Here, we describe a patient who developed cerebral RN after receiving conventional RT to an extra-cranial site, while he was receiving immune checkpoint inhibitor (ICI) therapy.

Management of Childhood Migraine by Headache Specialist vs Non-Headache Specialists.

OBJECTIVE: This study aims to compare the management practices of a headache specialist with non-headache specialists in the treatment of children with migraine. The use of appropriate rescue medications and prophylactic agents, application of neuroimaging, and short-term outcomes are compared in children treated by the two groups of physicians. METHODS: A retrospective cohort study was conducted by utilizing the electronic medical records of children 3-18 years of age with migraine, who were evaluated at a tertiary care children's hospital from 2016 to 2018. RESULTS: Of the 849 patients who met the study criteria, 469 children were classified as having chronic migraine or high-frequency episodic migraine and were followed-up on at least 1 occasion by the neurologists. Imaging was obtained in 66.5% of all children with migraine. The headache specialist used 5-HT agonists ("triptans") for migraine management in 56.7% (76/135) of cases compared to non-headache specialists who prescribed them in 28.7% (96/334) of cases (P < .001). Of the children with chronic migraine, the headache specialist evaluated 135 patients while the non-headache specialists treated 334 children. Non-headache specialists prescribed prophylaxis in the form of natural supplements more frequently (63.8% of cases) compared to the headache specialist (38.5% of children) (P < .001). Moreover, prophylaxis with prescription drugs was utilized more often by headache specialist (66.7%) than non-headache specialists (37.4%) (P < .001). CONCLUSIONS: Imaging appears to be commonly recommended by both headache specialists and non-headache specialists in children with migraine. The headache specialist was more likely to use triptans as rescue medications for pediatric migraine. Outcomes in the short-term were not statistically different whether children were being managed by the headache specialist or the non-headache specialists.