ABSTRACT
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment. In this review, the history, structure and mechanism of action of CAR-T, as well as the current status and challenges of CAR-T immunotherapy in acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma are summarized.
Subject(s)
Humans , Antigens, CD19 , Hematologic Neoplasms , Therapeutics , Immunotherapy , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , T-LymphocytesABSTRACT
<p><b>OBJECTIVE</b>To investigate the efficacy of hematopoietic stem cells cryopreserved by ladder-style freezing from low temperature refrigerator to liquid nitrogen in treatment of hematological malignancies, and to analyze the survival condition of patients after hematopoietic stem cell transplantation.</p><p><b>METHODS</b>The coyoprotectant formed by 3% hydroxyethyl starch, 4% albumin and 5% dimethyl sulfoxide (DMSO) was need for cryopreservation of hematopoietic stem cells,which were first placed in -80C low temperature refrigerator and then were stored in -196C liquid nitrogen tank. 98 cases of hemafologic malignancies (io cases of ALL, 24 cases of AML, L-cases of MM and 53 case of malignant lymphoma) were selected from January 2002 to December 2016, and recived transplantatin auto-hematopoiehc stem cells cryopresorved by above-mentined method. The overall survival rate (OS), progression-free survival (PFS) were analyzed statistically.</p><p><b>RESULTS</b>One case failed in implantation due to intracranial hemorrhage and the other 97 cases all succeeded in hematopoietic reconstitution. The average time needed for neutrophil count ≥0.5×10/L was 9.24±1.89 d, and the average time needed for blood platelet ≥20×10/L without platelet transfusion for 3 days was 11.04±1.84 d. The median survival time was 47.6 months (1-80 months). The 3 and 5 year OS rates were (97.2±1.9) %, (84.2±4.6) % and (77.8±5.6) %, respectively. 3- and 5-year PFS of patients were (74.4±5.1)% and (61.2±6.2)%.</p><p><b>CONCLUSION</b>ladder-style freezing from low temperature refrigerator to liquid nitrogen can reach the same clinical transplantation effect with traditional programmed cooling freezing method in autologous hematopoietic stem cells transplantation. moreover the incidence of complications after transpeantatim does not show increase.</p>
ABSTRACT
BACKGROUND:It has been reported that 70％ of patients with chronic myeloid leukemia (CML) are negative for cytogenetic and genetic markers within 1-5 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT),but there are still some patients who have repeatedly varied outcomes in cytogenetic and genetic marker detection.Overall,the negative rate is up to 89.5％ at 3-12 months after allo-HSCT.OBJECTIVE:To monitor the changes in cytogenetic and genetic marker expression and to explore the prognostic significance in CML patients undergoing allo-HSCT.METHODS:Seventeen CML patients who had undergone allo-HSCT were enrolled.Chromosome G banding pattern of the bone marrow from these patients were analyzed using short-term culture method and direct method at 30 days,2,3,4,6,12,24,36,48,60,72 months after allo-HSCT.Dual-color fluorescence in situ hybridization was used to detect bcr-abl fusion gene;bcr-abl expressions in primary bone marrow ceils from CML patients were detected using RQ-PCR.Results and conclusion:There were 8/17 cases of male patient/male donor and 7/17cases of male patient/female donor (compatriots).46XX karyotype (women) was detected by multiple reexaminations after transplantation,and there was no Y chromosome or other aberration of chromosome karyotype in their karyotype.Among the 17 cases,1 case of female patient/female donor (compatriots) and 1 case of female patient/male donor (unrelated) manifested 46 XY chromosome karyotype and bcr-abl positive at 1 month after transplantation;after 4 months,these two cases still maintained 46 XY chromosome karyotype but bcr-abl negative;after 4-96 months,the karyotype continued to remain as 46 XY,and bcr-abl (-).Among the 17 cases,1 case of male patient/male donor of full-matched compatriot (brother) manifested that Ph chromosomal bcr-abl gene continuously expressed within 1-12 months after allo-HSCT;then the cases was given donor lymphocyte infusion,and the bcr-abl expression returned to be negative at 48 months after transplantation.To conclude,chromosomal karyotype analysis and bcr-abl fusion gene monitoring provide important reference value for subsequent treatment options and prognosis judgment for CML patients with allo-HSCT.