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Patients with lymphoid hematologic malignancies have a poor prognosis after developing SARS-CoV-2 infection, and their seropositivity rate after SARS-CoV-2 vaccination is lower than that of the healthy population. Since most clinical trials of SARS-CoV-2 vaccines do not include immunodeficient populations, the safety and efficacy of various types of SARS-CoV-2 vaccines for patients with lymphoid hematologic malignancies are unclear. Therefore, physicians should decide whether patients with lymphoid hematologic malignancies receive SARS-CoV-2 vaccination and the timing, type and dose of vaccine after taking into full consideration the patient's immune status, type of treatment and the risk of SARS-CoV-2 infection.
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Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.
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Objective@#Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL.@*Methods@#The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without.@*Results@#The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) .@*Conclusions@#Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.
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Objective To explore the efficacy of hematopoietic stem cell transplantation (HSCT) for 5 patients with Ph-like acute lymphoblastic leukemia (ALL).Methods Fluorescent in situ hybridization (FISH) was performed for detecting the rearrangement of susceptibility genes.Combined therapy of chemotherapy and ruxolitinib were applied,followed by HSCT.Those failing to achieve complete remission (CR) received an infusion of chimeric antigen T-cells (CAR-T),followed by HSCT once CR was achieved.Four patients accept allogenic HSCT while another auto HSCT.Results Three of them achieved CR after chemotherapy and ruxolitinib.The remaining 2 patients got CR after CAR-T.Four patients remained in CR after HSCT.Early relapse occurred in 1 patient after HSCT.Conclusions Combined therapy of chemotherapy,ruxolitinib and CAR-T are necessary for Phlike ALL patients.HSCT after an initial CR improve patient prognosis.
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Objective To improve the understanding of the diagnosis and treatment of Philadelphia (Ph) chromosome-like acute lymphoblastic leukemia (ALL) with EBF1-PDGFRB-positive. Methods One case of Ph-like ALL with EBF1-PDGFRB-positive from the First Affiliated Hospital of Soochow University was reported. Whole exome sequencing was applied to detect the EBF1-PDGFRB fusion gene. Fluorescence in situ hybridization (FISH) was used to detect minimal residual disease. Comprehensive treatments including chemotherapy, imatinib and chimeric antigen T-cell (CAR-T) therapy were utilized. Results EBF1-PDGFRB fusion gene in the bone marrow samples was detected by using whole exome sequencing at early diagnosis. The rearrangement of PDGFRB showed continuous negative after comprehensive therapy. The patient achieved continuous molecular remission for 22 months. Conclusions The comprehensive treatments include combined chemotherapy, CAR-T therapy and tyrosine kinase inhibitor can promote the continuous of major molecular remission for EBF1-PDGFRB-positive Ph-like ALL patients.
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Objective curcumin can suppress the proliferation , induce apoptosis and partial differentiation , and inhibit the migration of many kinds of tumor cells .The aim of this study was to investigate the expressions of mitogen-activated protein kinase (MAPKs) and matrix metalloproteinases (MMPs) when the proliferation of human multiple myeloma RPMI8226 cells was inhibited by curcumin in vitro, and to reveal the antitumor molecular mechanism of curcumin . Methods RPMI8226 cells were treated with various concentrations of curcumin for different periods of times .The inhibitory rate of curcumin on cell proliferation was detected by MTT assay , the cell cycle analyzed by flow cytometry , the protein levels of MAPKs measured by Western blot , and the activity of MMPs analyzed by Gelatin zymography . Results Curcumin inhibited the proliferation of RPMI 8226 cells in a time-and dose-dependent manner , and the cell cycle was arrested in the G 2/M phase ([12.72 ±0.68]%vs [4.79 ±0.15]%).The expressions of JNK and p-JNK showed a con-centration-dependent increase in the RPMI8226 cells treated with curcumin at 6.25, 12.50, and 25.00 μmol/L, respectively (P0.05).In addition, the activities of MMP-2 and MMP-9 were decreased in a dose-depend-ent manner in the supernatant of RPMI8226 cells ( P <0.01). Conclusion A certain concentration of curcumin could not only acti-vate the JNK signalling pathway of the MAPKs family and induce the apoptosis of RPMI8226 cells, but also inhibit the activity of MMPs and influence the invasion and metastasis of RPMI 8226 cells.
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<p><b>OBJECTIVE</b>To investigate the expressions of mitogen-activated protein kinases (MAPKs) and matrix metalloproteinases (MMPs) in apoptotic human T cell lymphoma Jurkat cells induced by curcumin in vitro and explore the possible molecular mechanisms of curcumin-induced apoptosis.</p><p><b>METHODS</b>Jurkat cells were treated with different concentrations of curcumin, and the cell proliferation and cell cycle changes were detected by MTT assay and flow cytometry, respectively. Western blotting and gelatin zymography were employed to examine the protein expression levels of MAPKs and MMPs activity in the exposed cells.</p><p><b>RESULTS</b>Curcumin inhibited the proliferation of Jurkat cells in a time- and dose-dependent manner, and caused cell cycle arrest in G0/G1 phase. Treatment of Jurkat cells with 25, 50, and 75 µmol/L curcumin resulted in a concentration-dependent increase of JNK and p-JNK expressions (P<0.01) without significantly affecting the expressions of ERK1/2 and P38 MAPK or the activity of MMP-2 and MMP-9.</p><p><b>CONCLUSION</b>Curcumin within the concentration range of 6.25-25.00 µmol/L can induce apoptosis and cell cycle arrest of Jurkat cells, the mechanism of which might involve the activation of JNK pathway but not the MMPs.</p>
Subject(s)
Humans , Apoptosis , Cell Cycle , Cell Division , Cell Proliferation , Curcumin , Pharmacology , Flow Cytometry , Jurkat Cells , MAP Kinase Signaling System , Matrix Metalloproteinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Matrix Metalloproteinases , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Mitogen-Activated Protein Kinases , Metabolism , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
Objective To explore the possible effects on differentiation of SHI-1 cells induced by puerariae radix flavones(PRF)in vitro.Methods SHI-1 cells were treated with PRF in various concertration,then the inhibitory effects of cell proliferation were detected by MTT assay,the cell cycles were analyzed by flow cytometry(FCM),the cells reduction rates were detected by NBT reduction test,and the expression of CD11b and CD14 were tested by FCM.Results 10-50 μg/ml PRF could inhibit the proliferation of SHI-1 cells in a time-and dose-dependent manner,and the cell cycles were arrested in S phase.When SHI-1 cells were treated with 10,30 and 50 μg/ml PRF in 48 houres respectively,the NBT reduction rates of cells were increased in a dose-dependent with PRF(P＜0.05),and the expression of cells surface differentiation antigen CD14 was also increased along with the concentration of PRF.Conclusion The SHI-1 cells could be induced to differentiation partially after treated with 10,30 and 50 μg/ml PRF in vitro.