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1.
Journal of Leukemia & Lymphoma ; (12): 229-234, 2022.
Article in Chinese | WPRIM | ID: wpr-929765

ABSTRACT

Objective:To explore the efficacy and safety of anti-B cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) for the retreatment of relapsed and refractory multiple myeloma (RRMM).Methods:The clinical data of 10 RRMM patients who received anti-BCMA CAR-T therapy for the second time (CART2) in Henan Province Hospital of Traditional Chinese Medicine due to failure or recurrence after their first anti-BCMA CAR-T (CART1) therapy from January 2017 to June 2021 were retrospectively analyzed. The treatment, efficacy and adverse events of patients receiving CART2 therapy were summarized; and the objective response rate (ORR), median duration of response (DOR) and incidence of adverse reactions were compared between CART1 and CART2.Results:Among 10 patients, 8 were males and 2 were females, with a median age of 57 years (41-70 years). Patients' 3-month ORR after CART1 therapy was 90%, and the median DOR was 16.0 months (3.0-27.0 months). CART2 used human-derived anti-BCMA CAR-T to treat 6 cases and mouse-derived anti-BCMA CAR-T to treat 4 cases. The 3-month ORR of patients receiving CART2 therapy was 40%, and the median DOR was 8.5 months (3.0-11.0 months). Among 9 patients who received mouse-derived anti-BCMA CAR-T in CART1 therapy, 4 of them received the same product again and none of them showed curative effect. Among 6 patients retreated with human-derived anti-BCMA CAR-T, 4 patients (66.7%) of them achieved partial remission (PR) or better. During CART1 therapy, 10 patients developed grade 1-2 cytokine release syndrome (CRS), and 7 patients developed different degrees of decrease in leukocyte, neutrophil absolute count (ANC) and platelet. Among patients who achieved effective outcomes after receiving CART2 therapy, 4 patients of them developed grade 1-2 CRS, and different degrees of decrease in white blood cell, ANC and thrombocytopenia. Immune effector cell-related neurotoxicity syndrome was not observed.Conclusions:Anti-BCMA CAR-T is effective and safe to retreat RRMM. The ORR and DOR of patients receiving CART2 therapy are lower than those of patients receiving CART1 therapy. CRS and cytopenia are common adverse reactions.

2.
Chinese Journal of Hematology ; (12): 858-862, 2017.
Article in Chinese | WPRIM | ID: wpr-809456

ABSTRACT

Objective@#To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance.@*Methods@#The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed.@*Results@#The rates of overall surviva1 (OS) in high expression and low expression groups were 25.0 months and 15.0 months, respectively (P<0.05) . Relapse free survival (RFS) in high expression and low expression groups were 21.4 months and 11.2 months, respectively (P<0.05) . Significantly higher level hemoglobin, complete remission rate and proportion of wild type NPM1 expression in the high expression of miRNA-181a group were observed when compared with the lower expression of miRNA-181a group (P<0.05) . Multivariate Cox regression analysis showed miRNA-181a overexpression was an independent prognostic factor for CN-AML (HR=2.219, 95%CI 1.601~2.432, P=0.018) .@*Conclusion@#Higher expression of miRNA-181a was a good prognostic factor independent of clinical parameters and high frequency gene mutations, which implicated that the miRNA-181a expression level could be used as an important prognostic indicator of AML patients with normal karyotype.

3.
Chinese Journal of Hematology ; (12): 131-134, 2015.
Article in Chinese | WPRIM | ID: wpr-278894

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanisms of DelCD11-279 of factor XIII subunit A mRNA in the pathogenesis of hereditary factor XIII deficiency.</p><p><b>METHODS</b>The recombinant plasmids containing pET-22b(+)/FXIIIA of normal subject and proband's mother and pET-22b(+)/FXIIIA-Del of the proband were constructed and transformed into E. coli BL21. Expressing protein was analyzed by the SDS-PAGE and purified by Ni-NTA resin. Purified proteins were detected by the Western-blot. The activity of purified protein was detected by the incorporation test with EZ-LinkTM5-(Biotinamido) Pentylamine.</p><p><b>RESULTS</b>The recombinant plasmids containing pET-22b(+)/FXIIIA and pET-22b(+)/FXIIIA-Del which constructed and identified successfully by enzyme digestion and PCR, were transformed into E. coli BL21 and efficiently expressed by IPTG induction. The molecular weights of expressing proteins are 83 200 and 51 900 by the SDS-PAGE. Expressing proteins were purified by Ni-NTA resin, and were proved to be human FXIIIA proteins by Western-blot. Purified protein activity of proband's mother and proband was 95.87% and 0 of the purified FXIIIA protein activity from the normal subject, respectively.</p><p><b>CONCLUSION</b>DelCD11-279 of FXIIIA mRNA which encoding a 464 amino acids of inactive FXIIIA protein is one of the molecular mechanisms resulting in FXIII deficiency in the patient.</p>


Subject(s)
Humans , Escherichia coli , Factor XIII , Factor XIII Deficiency , Polymerase Chain Reaction , RNA, Messenger , Sequence Deletion
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