BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Objective:To investigate the clinical manifestations, diagnosis, treatment and prognosis of Kawasaki disease (KD) complicated with acute abdomen in children.Methods:Clinical manifestations, laboratory examinations, abdominal B-ultrasound scans, abdominal plain films, abdominal CT findings, coronary artery lesions and prognosis of 16 children with KD and acute abdomen admitted to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from August 1, 2015 to July 31, 2019 were retrospectively analyzed.The measurement data of age, leukocyte, hemoglobin, platelet and biochemical indexes are expressed by M (range). Results:A total of 16 cases were included, involving 7 males and 9 females aged 4 years and 8 months (7 months to 8 years). Among them, 9 cases of KD complicated with cholecystitis, 5 cases with intestinal obstruction, 2 cases with acute appendicitis, 2 cases with necrotizing enterocolitis, 2 cases with acute peritonitis and 1 case with acute pancreatitis.There were 3 cases complica-ted with 2 or more kinds of acute abdomen diseases.All 16 patients had symptoms of abdominal pain, 7 cases had vomiting, 4 cases had obvious abdominal distension and 1 case had bloody stool.Abdominal B-ultrasound was performed in all cases, and 8 cases showed enlargement of gallbladder and edema and thickening of gallbladder wall, 2 cases of appendicitis, 2 cases of intestinal obstruction and 1 case of pancreatic enlargement.Abdominal plain film examination was performed in 8 cases, suggesting necrotizing enterocolitis in 2 cases and intestinal obstruction in 2 cases.Abdominal CT examination was performed in 3 cases, including edema of gallbladder wall in 1 case, peritonitis in 1 case, intestinal obstruction in 2 cases and enlargement of pancreas in 1 case.All the 16 cases were treated with pulsed intravenous immunoglobulin (IVIG) at 2 g/kg and antiplatelet agents.Eight IVIG-resistant cases were treated with the second dose of IVIG at 2 g/kg, among whom, 4 children still had fever and intravenous Methylprednisone was given.Two cases underwent enterostomy and abdominal puncture drainage.All the 16 children were followed up until 6 months after discharge, and 4 cases (25%) were complicated with coronary artery aneurysm (CAA) during the acute stage or follow-up period.Conclusions:KD complicated with acute abdomen is more commonly manifested as cholecystitis and intestinal obstruction.Besides the classic symptoms of KD, abdominal pain and vomiting are the most common in KD with acute abdomen.Abdominal ultrasound, plain film and CT examinations are conductive to the early diagnosis of KD complicated with acute abdomen.In addition, the incidence of IVIG-resistance and CAA is relatively high in children with KD complicated with acute abdomen.

Chimeric antigen receptor-T (CAR-T) cell therapy, as a novel cellular immunotherapy, has dramatically reshaped the landscape of cancer treatment, especially in hematological malignancies. However, relapse is still one of the most troublesome obstacles to achieving broad clinical application. The intrinsic factors and superior adaptability of tumor cells mark a fundamental aspect of relapse. The unique biological function of CAR-T cells governed by their special CAR construction also affects treatment efficacy. Moreover, complex cross-interactions among CAR-T cells, tumor cells, and the tumor microenvironment (TME) profoundly influence clinical outcomes concerning CAR-T cell function and persistence. Therefore, in this review, based on the most recent discoveries, we focus on the challenges of relapse after CAR-T cell therapy in B-cell malignancies from the perspective of tumor cells, CAR-T cells, and the TME. We also discuss the corresponding basic and clinical approaches that may overcome the problem in the future. We aim to provide a comprehensive understanding for scientists and physicians that will help improve research and clinical practice.
Cell- and Tissue-Based Therapy ; Humans ; Immunotherapy, Adoptive/methods* ; Neoplasm Recurrence, Local/therapy* ; Neoplasms/pathology* ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Tumor Microenvironment

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult ; Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Chimeric Antigen ; Recurrence

Objective:This study aimed to evaluate the safety and efficacy of humanized CD19-targeted chimeric antigen receptor T-cell (CAR-T) in patients with relapsed/refractory acute B cell lymphoblastic leukemia (R/R B-ALL) .Methods:The clinical data of 41 patients with R/R B-ALL treated with humanized CD19-targeted CAR-T cells in the First Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to July 2021 were analyzed.Results:Cytokine release syndrome occurred in all patients, and 63.4% (26/41) were grades 1-2. Immune effector cell-associated neurotoxicity syndrome developed in three patients. On median day 15 (9-47) , the complete remission rate was 95.1% (39/41) , of which 38 patients tested negative for bone marrow minimal residual disease detected by flow cytometry. Among the 39 patients with complete remission, 17 patients did not receive further treatment, and 70.6% (12/17) remained in remission at the end of follow-up, with a progression-free survival of 11.6 months of the two patients with the earliest infusion. Another 17 patients underwent consolidation allogeneic hematopoietic stem cell transplantation (10 cases) or CD22 CAR-T cell sequential therapy (seven cases) after remission, and 76.5% (13/17) of the patients were still in remission at the end of follow-up. The remaining five patients who did not receive consolidation therapy relapsed at a median of 72 (55-115) days after CAR-T cell therapy.Conclusion:In patients with R/R B-ALL, the humanized CD19-targeted CAR-T cells had a high response and manageable toxicity.

The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.
Cell- and Tissue-Based Therapy ; Humans ; Immunotherapy, Adoptive ; Lymphoma/therapy* ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen

Kawasaki disease (KD) is an acute febrile eruption disease mainly caused by systemic vascular di-seases, often is diagnosed in infants and young children, and mainly involve small and medium arteries of the whole body.KD can be complicated by coronary artery disease, carditis, interstitial pneumonia, aseptic meningitis and so on.KD complicated with acute abdomen, such as cholecystitis, pancreatitis and intestinal obstruction, has also been paid attention to in recent years.Early identification of acute abdomen as a manifestation of KD complications and timely treatment can help improve the prognosis of coronary artery disease and acute abdomen caused by KD.

Objective To investigate the value and advantage of ultrasound guided intermuscular groove and suprascapular nerve block combined with general anesthesia in shoulder arthroscopy.Methods 40 American Society of Anesthesiologists (ASA) Ⅰ-Ⅱ patients undergoing elective arthroscopic shoulder surgery were randomly divided into two groups.Patients in group A were treated with general anesthesia,while patients in group B were treated with brachial plexus and suprascapular nerve block combined with general anesthesia.Mean arterial pressure (MAP),heart rate (HR) and visual analogy score (VAS) were measured at preoperative (To),5 min after the beginning of the surgey (T1),30 min after the beginning of the surgey (T2),at the end of the surgery (T3),and 30 min after removing laryngeal mask (T4).Bispectral index (BIS) was recorded at T1 and T2.The operation time,extubation time,dosage of opioids (sufentanyl),dosage of propofol,visual analogue scale (VAS) scores at awake time in post anesthesia care unit (PACU),and 6 h,12 h,24 h after surgery.Results There were no significant differences in the BIS between two groups at T1 and T2 (P ＞ 0.05).Both the MAP and HR had no statistical significance at T0 (P ＞ 0.05).MAP and HR in group B were significantly lower than those in group A from T1 to T4 (P ＜ 0.05).Compared with group A,patients in group B had significantly shorter extubation time (P ＜ 0.05),smaller dosages of sufentanyl and propofol (P ＜ 0.05),lower VAS scores at awake time 6 h and 12 h after surgery (P ＜ 0.05).Conclusions Brachial plexus and suprascapular nerve block combined with general anesthesia can offer better anesthesia status,reduce dosage of opioids and propofol,and can provide effective analgesia in shoulder arthroscopy.