Tumor Lysis Syndrome following a Single Dose of Nivolumab for Relapsed Small-Cell Lung Cancer.

Tumor lysis syndrome (TLS) is an oncologic emergency most frequently associated with initial treatment of hematologic malignancies and high-tumor burden solid tumors such as small-cell lung cancer (SCLC). Most often, TLS is associated with cytotoxic chemotherapy. In the treatment of SCLC, a paradigm shift has taken place in which immunotherapy is often added to chemotherapy for extensive-stage disease in the frontline setting or as monotherapy in the relapsed setting. Nivolumab is a programmed death 1 receptor blocking antibody previously FDA indicated for the treatment of metastatic SCLC with progression after platinum-based chemotherapy and at least one other line of therapy. Nivolumab, like all immune checkpoint inhibitor therapies, is associated with immune-mediated adverse reactions; however, there are few reported cases of nivolumab-induced TLS. We present a case of nivolumab-induced TLS following a single infusion. An 86-year-old female with a history of widely metastatic SCLC with metastasis to the liver, bone, and lymph nodes presented to the hospital following a fall due to weakness, dizziness, slurred speech, nausea, vomiting, and abdominal pain occurring 6 days after receiving her first nivolumab infusion. After extensive evaluation, the patient was diagnosed with TLS with hyperkalemia, acute renal failure, hyperphosphatemia, and hypocalcemia. She was treated aggressively with intravenous fluids, rasburicase, and sodium polystyrene sulfate (Kayexalate®), which resulted in rapid improvement of her electrolytes and renal function. However, despite correction of electrolytes and overall symptomatic improvement, over the course of several days, the patient's condition rapidly deteriorated with increasing dyspnea, lethargy, confusion, and eventually death. TLS following nivolumab is exceedingly rare. This report highlights the potential risk of development of TLS with checkpoint inhibitor therapy.

High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature.

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.

Liver biopsy findings in patients with hematopoietic cell transplantation.

Liver dysfunction is a frequent complication after hematopoietic cell transplantation. Liver biopsy has an important role for confirming the diagnosis of graft-versus-host disease (GVHD) or other liver diseases. The histological features of GVHD are not specific, and GVHD and other coexisting diseases may be present in the same biopsy, which makes the histologic interpretation of the liver biopsy more complex and challenging. The aim of the study is to improve the present diagnostic criteria. Fifty-two liver biopsies were studied. Most biopsies (47, 92%) showed some features of GVHD. Five (9.6%) had no GVHD, 20 (38.5%) had possible GVHD, and 27 (51.9%) had likely GVHD. Histologic features were analyzed semi-quantitatively and scored. Bile duct damage and intraepithelial lymphocytes were significantly more frequent in likely GVHD groups. Bile duct injury score calculated as the sum of bile duct damage and intraepithelial lymphocytes score was 2.3 in no GVHD and possible GVHD groups, and 4.2 in likely GVHD group (P<.001). A bile duct injury score ≥4 correlated well with a diagnosis of GVHD, with sensitivity 74% and specificity 88%. Many cases (36; 70.6%) had a concurrent disease process. Drug-induced liver injury (8, 16%) and sinusoidal obstruction syndrome (6, 12%) are particularly important causes of liver dysfunction. Moderate degree of bile duct injury and intraepithelial lymphocytes were the most helpful histologic findings to confirm the diagnosis of GVHD. In addition, it is important for the pathologist to be aware of the etiologies of liver dysfunction other than GVHD.