Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in childhood. Survival for patients following relapse remains poor, and achieving complete remission (CR) after relapse is the first critical step to cure. Carfilzomib is a proteasome inhibitor with an acceptable safety profile and clinical activity in adults with multiple myeloma but has not been assessed in children. The primary objective of this phase 1b study was to assess the safety and tolerability of carfilzomib combined with vincristine, dexamethasone, asparaginase, and daunorubicin (VXLD) in children with relapsed and/or refractory ALL. METHODS: Patients aged 1-21 years (n = 24) received 4-week induction therapy with carfilzomib at dose levels of 27 mg/m2 (n = 3), 36 mg/m2 (n = 7), 45 mg/m2 (n = 4), and 56 mg/m2 (n = 10) in combination with VXLD. Patients achieving stable disease were offered further consolidation chemotherapy. Analyses were based on the safety evaluable population. RESULTS: Following dose escalation of carfilzomib, the recommended phase 2 carfilzomib dose was identified as 56 mg/m2 . Grade ≥3 hematological adverse events were common (83%, 20/24 patients), and serious treatment-emergent adverse events occurred in 58% (14/24) of patients. At the end of induction, CR/CR with incomplete platelet recovery (CRp)/CR with incomplete blood count recovery (CRi) was identified in 50% of patients (n = 12/24). By the end of consolidation, cumulative CR/CRp/CRi was identified in 58% of patients (n = 14/24). CONCLUSION: These data support the use of carfilzomib in pediatric patients with relapsed and/or refractory ALL.

Molecular characteristics and systemic treatment options of liposarcoma: A systematic review.

Liposarcoma (LPS) is a rare soft tissue sarcoma that develops from the differentiation of fat cells, typically occurring in the lower extremities and retroperitoneal space. Depending on its histological morphology and molecular changes, LPS can be divided into various subtypes, each exhibiting distinct biological behaviors. During treatment, especially for LPS arising in the retroperitoneum, the extent and quality of the initial surgery are critically important. Treatment strategies must be tailored to the specific type of LPS. Over the past few decades, the treatment of LPS has undergone numerous advancements, with new therapeutic approaches such as targeted drugs and immunotherapies continually emerging. This paper reviews the biological characteristics, molecular alterations, as well as surgical and pharmacological treatments of various LPS subtypes, with the aim of enhancing clinicians' understanding and emphasizing the importance of individualized precision therapy. With a deeper understanding of the biological characteristics and molecular alterations of LPS, future treatment trends are likely to focus more on developing personalized treatment plans to better address the various types of LPS.

[Design and application of a new transoral gastric tube for extraction and storage of gastric contents].

Difficulty in swallowing is a common symptom in stroke patients, and nasogastric tubes are routinely used to solve the nutritional support problem of these patients. The existing nasogastric tube have the disadvantages of causing aspiration pneumonia and patient discomfort. The traditional transoral gastric tube has no one-way valve switch and gastric content storage device, and cannot be fixed in the stomach, resulting in reflux of gastric contents, inability to fully understand the digestion and absorption of gastric contents, and accidental dislocation of the gastric tube, affecting further feeding and gastric content detection. For these reasons, the medical staff of the department of gastroenterology and colorectal surgery of Jilin University China-Japan Union Hospital designed a new transoral gastric tube that can extract and store gastric contents, and was granted a national utility model patent of China (ZL 2020 2 1704393.1). The device consists of collection, cannula and fixation modules. The collection module includes three parts. Gastric contents storage capsule, which can clearly visualize the gastric contents; three-way switch, which can be controlled by rotating the pathway, makes the pathway exist in different states, which is convenient for medical personnel to extract gastric juice, as well as perform intermittent oral tube feeding on the patient or close the pipeline, and reduce contamination and prolong the service life of the gastric tube; one-way valve, which can effectively avoid the contents of the reflux back into the stomach. The tube insertion module includes three parts. A graduated tube, which can enable the medical staff to effectively identify the insertion depth; a solid guide head, which makes the insertion of the tube through the mouth more smoothly; the gourd-shaped passageway, which effectively avoids the blockage of the tube. The fixation module is a water-filled balloon, which is properly filled with water and air. After the pipe is inserted through the mouth, it can be injected with water and gas properly to avoid accidental withdrawal of the gastric tube. Intermittent oroesophageal tube feeding of patients with dysphagia after stroke through a transoral gastric tube that can extract and store gastric contents can not only accelerate the recovery process of patients and shorten the hospitalization time, but also transoral enteral nutrition can effectively promote the recovery of patients' systemic systems, which has certain clinical use value.