Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.
Humans ; Receptors, Chimeric Antigen/therapeutic use* ; Immunotherapy, Adoptive ; Hematologic Neoplasms/therapy* ; Treatment Outcome

Objective:This study aimed to evaluate the effect of early tocilizumab intervention to relieve cytokine release syndrome (CRS) following chimeric antigen receptor T cell (CAR-T) therapy.Methods:Twenty-two patients with acute lymphoblastic leukemia who received tocilizumab to relieve CRS response after CAR-T cell infusion in our research center from October 2015 to July 2021 were retrospectively analyzed. According to the timing of tocilizumab intervention, patients were divided into the conventional and early intervention groups. Patients who received tocilizumab treatment after sustained high fever for 4 h were included in the early intervention group. The clinical data, CRS grade, and event-free survival (EFS) between the two groups were evaluated.Results:Compared with patients who used tocilizumab after severe CRS, no patients in the early intervention group died from CRS, and there was no increased risk of neurotoxicity. Eleven patients (84.62%) achieved complete remission with minimal residual lesions. The median EFS of patients in the early intervention and conventional groups was 2 (95% CI 0-5) and 7 (95% CI 3-11) months, respectively. Conclusion:Early tocilizumab intervention in patients with CRS reduces severe CRS and provides a more optimized therapeutic strategy for CRS caused by CAR-T cell therapy.

Objective To make analysis and diagnosis on backhand twist technique used by player A, who is the leading men’s player of national table tennis team, so as to provide references for improving his backhand twist technique. Methods The three-dimensional kinematics test and analysis were used. The backhand twist techniques of player A and those of player B who has good backhand twist techniques were compared by quantitative data and picture analysis. Results At the stage of swinging racket backward, the racket swing amplitude, shoulder angle and wrist angle of player A were significantly smaller than those of player B. The roll angle of trunk of player A was significantly larger than that of player B. At the stage of swinging and hitting the ball, the shoulder angle, elbow angle of player A were significantly bigger than those of player B, while the increasing amplitude of shoulder angle and elbow angle, as well as the changing amplitude in roll angle of trunk of Lin Guoyuan were significantly smaller than those of player B. At the stage of swinging racket forward, the shoulder angle and elbow angle of player A were significantly bigger than those of player B. The increasing amplitude of shoulder angle and elbow angle, as well as the roll angle of trunk and its changing amplitude of player A were significantly smaller than those of player B. Conclusions The racket swing amplitude of player A was smaller, and the distance between the racket and the ball of player A was close at the end of swinging racket backward stage. During swinging and hitting the ball stage, the hitting point was far from the body, the shoulder joint was not stable enough to support, so that the wrist was used more. The center of gravity was not enough to force forward, and the outburst power was not concentrated. At swinging racket forward stage, player A’s braking was not active enough, which affected the stability of hitting the ball. At hitting the ball stage, the torsion of the trunk was smaller, and the waist power was not concentrated. On the basis of unaffecting the forehand outburst power, player A should slightly adjust his backhand twisting technique, or appropriately increase the the racket swing amplitude and torsion of the body. In the process of hitting the ball, the sequence of outburst power was the waist, the forearm and the wrist.

Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton's tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin's lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.
Adult ; Aged ; Cell- and Tissue-Based Therapy ; Humans ; Immunotherapy, Adoptive ; Lymphoma, Mantle-Cell/therapy* ; Neoplasm Recurrence, Local ; Receptors, Chimeric Antigen

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P < 0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.
Cell- and Tissue-Based Therapy ; Humans ; Immunotherapy, Adoptive ; Lymphoma, Non-Hodgkin/therapy* ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen

Objective To analyze the clinical features, treatment outcomes and prognosis of patients with urinary tract lymphoma. Methods The clinical data of 16 patients in Tongji Hospital of Tongji University from January 2009 to April 2016 were collected and retrospectively analyzed. Results The median age of these patients was 68 years. The onset symptoms of 14 cases were related to urinary system and imaging studies of 10 cases showed masses in the urinary system. The onset regions of lymphoma included:4 cases were renal lymphoma, 5 cases were adrenal lymphoma, 5 cases were testicular lymphoma, 1 case was prostate lymphoma and 1 case was from urethral mouth. The histological type of 12 cases was diffuse large B-cell lymphoma and 10 patients were non-germinal center B cell-like (non-GCB) molecular profiling. Twelve cases belonged to Ann Arbor stages ⅢE- ⅣE, 10 cases had international prognostic index scores ≥3, and 7 cases had B symptoms. 10 patients were confirmed by surgery. Fourteen cases accepted rituximab-containing regimen chemotherapy. Five cases achieved complete response and 3 were partial response. Conclusions The clinical manifestations and imagine examination of patients with urinary tract lymphoma are lack of specificity. The clinical features are highly aggressive and most of the patients are diagnosed at advanced stage. The main histological type is diffuse large B-cell lymphoma and non-GCB molecular profiling. Treatment regimens include surgery combined with chemotherapy and radiotherapy. Earlier diagnosis and treatment may improve the survival of patients.

Objective: To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai. Methods: A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance. Conclusions The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.

OBJECTIVETo investigate the efficacy and side effects of the consecutive chemotherapeutic protocol, Tongji-96, for adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph-aALL).

METHODSA retrospective analysis was conducted on 95 cases of Ph-aALL patients treated between January 2004 and December 2012 with Tongji-96 regimen in Tongji hospital, Shanghai.

RESULTSAmong these 95 patients, the overall complete remission (CR) rate was 92.6%, 7-year overall survival (OS) and event-free survival (EFS) rates were (39.3±5.9)% and (31.5±5.3)%, respectively, with the median survival of 28 months. Based on multivariable COX proportional hazards regression model analysis, patients with the poor karyotype and failed to achieve CR after first course induction therapy had a higher risk of mortality compared to those who had good or normal cytogenetics and achieved CR after 1 course of induction treatment [the risk ratios (RR) were 3.380 (95% CI 1.530-7.463, P=0.003) and 3.005 (95% CI 1.522-5.933, P=0.002)，respectively]. By means of Kaplan-Meier analysis and Log-rank test，patients aged less than 60 years and successively achieved CR after first induction therapy had more favorable 7-year OS and EFS rates. Patients with normal karyotype and hyperdiploidy had significantly higher 2-year OS and EFS rates compared with those with complex karyotype, t(4;11) translocation and other karyotypes.

CONCLUSIONAge (60 years as the cut-off)，treatment courses for achieving CR and cytogenetics were predictive factors for the prognosis of Ph-aALL from this retrospective study. As a comprehensive and sequential therapy protocol, Tongji-96 regimen was proved to obtain long-term survival, reduce risks for relapse and improve outcomes for part Ph-aALL patients.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; Chromosome Aberrations ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Karyotyping ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Remission Induction ; Retrospective Studies ; Translocation, Genetic

Objective To investigate the risk factors of delayed hemolysis after treatment in patients with malaria .Methods Eighty-nine cases of malaria were retrospectively analyzed .The incidence rate , time from treatment to delayed hemolysis and clinical features of delayed hemolysis after treatment in patients with malaria were investigated .The characteristics of demography ,etiology and laboratory data were compared between delayed hemolysis group and non-delayed hemolysis group .The t test ,χ2 test and Fisher exact test were used for comparison between groups .Results A total of 89 cases of malaria infection were included and 8 cases were diagnosed with delayed hemolysis after treatment among them , with incidence rate of 8 .99% .Patients developed delayed hemolysis after anti-malarial treatment with a median of 7 .5 d and patients recovered from hemolysis after the usage of glucocorticoid with a median of 2 .5 d .The 8 cases were all infected with Plasmodium f alciparum ,and 4 of which had high parasitemia . None of the patients with delayed hemolysis came from epidemic area ,while 28 of the patients without non-delayed hemolysis came from epidemic area .The difference was statistically significant (P=0 .042 , Fisher unilateral exact test) .The average level of minimum hemoglobin was (44 .87 ± 11 .58) g/L in patients with delayed hemolysis ,which was significantly lower than that of non-delayed hemolysis group (108 .35 ± 19 .72) g/L (t= -8 .923 , P< 0 .01) .Conclusion Plasmodium falciparum infection , hyperparasitemia and having no immunity against malaria may be risk factors of delayed hemolysis after treatment .

Objective To analyse protein tyrosine phosphatase 1B (PTP1B) gene mutation in myeloproliferative neoplasms (MPN).Methods DNA sequencing technology was used to detect DNA sequences of PTP1B in MPN patients (n =84) and normal controls (n =37).Results For Exon1-6,Exon9 and Exon10,84 cases of MPN patients and 37 cases of control group were not detected mutation.For EXON 8,18 of 84 MPN patients had Exon8 C/T heterozygous mutation and 10 of 37 normal controls were detected C/T heterozygous mutation.There was no significant difference between MPN patients and normal controls (x2 =0.453,P =0.501).Exon7 was detected in 38 MPN patients and 2 cases of patients were found C/T heterozygous mutation,while in the control group,1 case with G/C heterozygous mutation.All of the cases were not detected homozygous mutation.Conclusion Using DNA sequencing technology to detect gene mutations of PTP1B,there is no significant difference between MPN patients and normal controls.