Severe febrile neutropenia and pancytopenia in a patient with advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab: a case report.

Background: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course. Case Description: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a fever of 39.0 ℃ 10 days after therapy initiation. He presented 5 days later with persistent fever as well as a headache, vomiting, chills, generalized pain, fatigue, mild abdominal discomfort, and a burning rash present on his neck and face. Complete blood counts showed severe neutropenia [absolute neutrophil count (ANC) of 90 cells/µL], leukopenia [white blood cell (WBC) count 500 cells/µL], thrombocytopenia [platelet count (PC) 18,000 cells/µL], and mild anemia (hemoglobin level 12.6 gm/dL). Imaging findings showed colitis on computed tomography (CT). Atezo/bev therapy was discontinued. Treatment plan constituted of cefepime and filgrastim, a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia, metronidazole for colitis, and intravenous methylprednisolone for immune-related toxicities. The patient fully recovered after 4 days of admission. Conclusions: In conclusion, we observed temporary severe febrile neutropenia and pancytopenia during systemic immunotherapy in a patient with unresectable HCC. Healthcare providers should consider hematological irAEs (hem-irAEs) in patients after the administration of ICIs.

Venous thromboembolism in adrenocortical carcinoma: a retrospective analysis.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. PATIENTS AND METHODS: We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. RESULTS: VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. CONCLUSION: Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.

Thrombosis risk prediction in lymphoma patients: A multi-institutional, retrospective model development and validation study.

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients.

Mechanical Venous Thrombectomy for Deep Venous Thrombosis in Cancer Patients: A Single-Center Retrospective Study.

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (< 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients' VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected.

Management of DOAC-related bleeding in cancer patients: a single center-case series.

Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient's specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients.