Treatment with Granulocyte-colony Stimulating Factor (G-CSF) is not associated with Increased Risk of Brain Metastasis in Patients with De Novo Stage IV Breast Cancer.

Background: Survival outcome after developing brain metastasis is poor and there is an unmet need to identify factors that can promote brain metastasis. Granulocyte-colony stimulating factor (G-CSF) is given to support neutrophil recovery after myelosuppressive chemotherapy to some patients. However, there is emerging evidence that neutrophils can promote metastasis, including through the formation of neutrophil extracellular traps (NETs), scaffolds of chromatin with enzymes expelled from neutrophils to the extracellular space. In animal models, G-CSFs can induce NETs to promote liver and lung metastasis. The primary objective of this study was to test the association between G-CSF use and the later incidence of brain metastasis. Methods: Patients with de novo Stage IV breast cancer, without known brain metastasis at the time of initial diagnosis, were identified from electronic medical records covering the period from 1/1/2013 to 12/31/2020 at Northwell Health. Univariate and multivariate logistic regression models were used to test the association between variables of interest, including G-CSF use, and brain metastasis. Results: A total of 78 patients were included in the final analysis. Among those 78 patients, 24 patients (30.8%) had received G-CSF along with chemotherapy at least once. In logistic regression models, G-CSF use was not a significant factor to predict brain metastasis (OR 1.89 [95%CI 1.89-5.33]; P=0.23). Interestingly, in multivariate logistic models, pulmonary embolism (PE)/deep venous thrombosis (DVT) was a significant predictive factor of brain metastasis (OR 6.74 [95%CI 1.82-25.01]; P=0.004) (38.5% vs 21.5%). Conclusions: The use of G-CSF was not associated with increased risk of brain metastasis in patients with de novo Stage IV breast cancer. Interestingly, PE/DVT, which can be associated with elevated NETs, was associated with brain metastasis. Further studies are warranted to determine whether DVT/PE with or without elevated NETs levels in the blood, is predictive of developing brain metastasis in patients with de novo Stage IV breast cancer.

Immune thrombocytopenic purpura and acute liver injury after COVID-19 vaccine.

A 26-year-old woman was sent to the emergency room by her primary care physician for a new petechial rash and thrombocytopenia 2 weeks after receiving the Moderna mRNA-1273 SARS-CoV-2 vaccine. Her hospital course was complicated by transaminitis. Her platelet count improved to normal on hospital day 5 after receiving intravenous steroids and intravenous immunoglobulin to treat her suspected diagnosis of immune thrombocytopenic purpura. Extensive workup for her thrombocytopenia and transaminitis was unremarkable including ruling out infectious, autoimmune and toxic causes. A liver biopsy was unrevealing and her transaminitis was improved on discharge. Although not proven, the temporal relationship of her vaccination with thrombocytopenia and abnormal liver enzymes points towards the Moderna mRNA-1273 SARS-CoV-2 vaccine as the most likely inciting factor.

Acquired haemophilia A: successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents.

Acquired haemophilia A (AHA) is a rare and possibly fatal autoimmune disorder that is challenging to treat. Although a majority of cases are idiopathic, AHA can also be associated with an underlying malignancy, autoimmune disorder, pregnancy, infection or certain medications. The diagnosis and treatment of AHA require a specialist with both clinical and laboratory expertise. The goal of treatment is aimed at achieving haemostasis as well as eradicating factor inhibitors. We present a patient with AHA and life-threatening haemorrhage who was successfully treated with a combination of haemostatic agents and a triple-drug immunosuppressive regimen. In reviewing recent studies and published guidelines, we advocate that a newer agent, emicizumab, can potentially be incorporated into the treatment protocol for AHA given its promising performance in the realm of congenital haemophilia.

Pancytopenia after administration of hyperthermic intraperitoneal chemotherapy with mitomycin-C: local therapy and systemic toxicity.

Cytoreductive surgery (CRS) coupled with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of treatment for many cancers with peritoneal metastasis. Mitomycin-C (MMC), the most common chemotherapy utilized with HIPEC, is associated with neutropenia but the degree of hematologic toxicity is unclear when splenectomy is included as part of CRS with MMC. We present an interesting case of pancytopenia following treatment with HIPEC using MMC and comment on the possible role of splenectomy in exacerbating its cytotoxic effects. Our unique case highlights potential hematologic toxicity following MMC-HIPEC and splenectomy. It suggests that spleen removal may enhance toxicity profiles of chemotherapy such as MMC. Because MMC is the preferred agent of choice used in CRS-HIPEC, future studies should investigate optimal MMC dosing and patient selection when splenectomy is performed to balance survival benefit with hematologic toxicities.

Vemurafenib-induced pancreatitis in a patient with recurrent hairy cell leukaemia.

Recent studies have shown that BRAF inhibitors, such as vemurafenib, are effective in inducing long periods of remission in relapsed hairy cell leukaemia. Acute pancreatitis is one of the rare complications that is reported with vemurafenib use. As severe pancreatitis can be life threatening, physicians should be vigilant of this side effect and promptly treat patients that develop clinical signs and symptoms while receiving vemurafenib. We present an interesting case of vemurafenib-induced pancreatitis that not only resolved but also did not recur after reintroduction of the drug at a reduced dose.

A Rare Case of Gemcitabine-Induced Pulmonary Hypertension.

CONTEXT: Gemcitabine is the backbone of systemic treatment of locally advanced and metastatic intrahepatic cholangiocarcinoma. In recent literature, gemcitabine has been linked to various pulmonary side effects. CASE REPORT: We report a case of an 82-year-old male who developed acute pulmonary hypertension after receiving one cycle of gemcitabine for metastatic cholangiocarcinoma. His symptoms began with fatigue associated with shortness of breath and cough that worsened despite dose reduction. He developed new onset bilateral pulmonary effusions and an echocardiogram revealed findings consistent with pulmonary hypertension. A computed tomography (CT) angiogram was negative for pulmonary thromboembolism. Although he was promptly treated with diuretics and steroids, the patient could not tolerate any further therapy. CONCLUSION: Gemcitabine-induced pulmonary hypertension is rare and can be challenging to diagnose, as it remains a diagnosis of exclusion. However, physicians should be vigilant of new pulmonary symptoms, as delayed treatment can cause significant patient morbidity and mortality.