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1.
Chinese Journal of Hematology ; (12): 728-736, 2023.
Article Dans Chinois | WPRIM | ID: wpr-1012221

Résumé

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.


Sujets)
Adulte , Humains , Adolescent , Mésilate d'imatinib/effets indésirables , Incidence , Antinéoplasiques/effets indésirables , Études rétrospectives , Pyrimidines/effets indésirables , Leucémie myéloïde chronique BCR-ABL positive/traitement médicamenteux , Résultat thérapeutique , Benzamides/effets indésirables , Leucémie myéloïde en phase chronique/traitement médicamenteux , Aminopyridines/usage thérapeutique , Inhibiteurs de protéines kinases/usage thérapeutique
2.
Chinese Journal of Hematology ; (12): 404-407, 2018.
Article Dans Chinois | WPRIM | ID: wpr-1011772

Résumé

Objective: To evaluate the efficacy and safety of a domestic human plasma derived coagulation Factor Ⅸ concentrate (pd-FⅨ) in patients with hemophilia B. Methods: The study was a multicenter, open-label and single-arm study. The efficacy of pd-F Ⅸ was evaluated by objective performance criteria. The doses of pd-FⅨ were calculated according to the bleeding symptom and disease severity. The infusion efficiency of pd-FⅨ and improvement of bleeding symptoms were measured at 30 minutes and (24±4) h after the first infusion, respectively. Adverse events were recorded. Viral infection and FⅨ inhibitor were detected 90 d after the first infusion. Results: All 36 subjects with hemophilia B were enrolled in the study. The median age of these patients was 31 years old and the median injection doses were 4 (1-17) times. The hemostatic effect of 27/36 (75.00%) and 9/36 (25.00%) acute bleeding events were rated as "excellent" and "better" , respectively. The recovery rate was 111.92% (65.55%-194.28%) at 30 minutes after infusion of FⅨ. There was no adverse event related to FⅨ. No reactivation of HBV, HCV or HIV and FⅨ inhibitor was detected at 90-104 d after the first FⅨ infusion. Conclusion: This domestically made human plasma derived FⅨ concentrate is safe and effective in the treatment of acute bleeding in patients with hemophilia B. Clinical trial registration: China food and Durg Administration, 2016L08027.


Sujets)
Adulte , Humains , Chine , Facteur IX , Hémophilie A , Hémophilie B/thérapie , Hémorragie , Plasma sanguin
3.
Journal of Experimental Hematology ; (6): 1366-1369, 2015.
Article Dans Chinois | WPRIM | ID: wpr-274034

Résumé

<p><b>OBJECTIVE</b>To investigate the humoral and cellular immune responses induced by MUC1-2VNTR DNA vaccine in multiple myeloma (MM) tumor-bearing mice.</p><p><b>METHODS</b>In vitro, multiple myeloma cells were transfected by plasmid pcDNA3.1-2VNTR/myc-hisB with Lipofectamine2000. The above-mentioned mouse myeloma cells were inoculated subcutaneously into female BALB/c mice for establishing tumor-bearing animal models. These female BALB/c mice were immunized with pcDNA-2VNTR/myc-hisB or pcDNA/myc-hisB. The cytotoxic T lymphocyte (CTL) activity was detected by the LDH method and the spleen lymphocyte proliferation activity was detected by CCK-8 method.</p><p><b>RESULTS</b>After immunization of BALB/c tumor-bearing mice with recombinant plasmid for 25 days, the tumor mass (0.5605 ± 0.2065 g) was significantly lighter than that in the empty plasmid control group (1.521 ± 0.6985 g) (P < 0.01) and the control group (1.5315 ± 0.5425 g) (P < 0.01). The difference of tumor mass was not statislically significant between empty plasmid control group (1.521 ± 0.6985 g) and the control group (1.5315 ± 0.5425 g) (P > 0.05). The CTL and NK cell activity was significantly higher in the group of intramuscular injection with recombinant plasmid than that in control group. The spleen lymphocyte proliferation was statistically significantly increased after being immunized with recombinant plasmid pcDNA3.1-2VNTR/myc-hisB, compared with empty vector (P < 0.01). The results showed that MUC1-2VNTR gene immunization could induce anti-tumor effect in MM tumor-bearing mice.</p><p><b>CONCLUSION</b>MUC1-2VNTR DNA immunization can elicit both humoral and cellular tumor specific immune response to multiple myeloma in MM tumor-bearing mice. It suggested that the MUC1-2VNTR DNA vaccine may be a potential treatment measure for patients with MM.</p>


Sujets)
Animaux , Femelle , Humains , Souris , Vaccins anticancéreux , Utilisations thérapeutiques , Vecteurs génétiques , Immunisation , Cellules tueuses naturelles , Allergie et immunologie , Activation des lymphocytes , Souris de lignée BALB C , Répétitions minisatellites , Mucine-2 , Génétique , Myélome multiple , Allergie et immunologie , Thérapeutique , Transplantation tumorale , Plasmides , Rate , Biologie cellulaire , Lymphocytes T cytotoxiques , Allergie et immunologie , Transfection , Vaccins à ADN , Utilisations thérapeutiques
4.
Journal of Experimental Hematology ; (6): 328-334, 2015.
Article Dans Chinois | WPRIM | ID: wpr-259590

Résumé

<p><b>OBJECTIVE</b>To compare the tumor-forming rate between the SCID and NOD/SCID mice to set up acute myeloid leukemia (AML) mouse model.</p><p><b>METHODS</b>The SCID and NOD/SCID mice were injected with HL-60 cells in to the abdominal cavity in order to contruct the AML mouse model. The gereral status of mice was observed, the positive rate of CD33 in bone marrow cells was detected by flow cytometry, the mouse model was identified by pathologic examination.</p><p><b>RESULTS</b>The tumor-forming rate in constructed model using SCID mouse was 30%, while the tumor-forming rate in constructed model using NOD/SCID mouse was 100%.</p><p><b>CONCLUSION</b>Compared with SCID mice, the tumor-forming rate in NOD/SCID mice injected with HL-60 cells is high, the incidence of AML is stable, suggesting that the NOD/SCID mouse model is more suitable to explore the pathogenesis of leukemia.</p>


Sujets)
Animaux , Humains , Souris , Modèles animaux de maladie humaine , Cytométrie en flux , Cellules HL-60 , Leucémie aigüe myéloïde , Souris de lignée NOD , Souris SCID
5.
Chinese Journal of Hematology ; (12): 200-203, 2012.
Article Dans Chinois | WPRIM | ID: wpr-345899

Résumé

<p><b>OBJECTIVE</b>To detect the platelet glycoprotein-specific antibodies in serum of thrombocytopenia patients and evaluate its diagnostic value for immune thrombocytopenia.</p><p><b>METHOD</b>Anti-GPIIb/IIIa, GPIb/IX and GPIa/IIa antibodies were assayed by ELISA kit (PAKUTO) in patients with thrombocytopenia.</p><p><b>RESULTS</b>The sensitivity and specificity of PAKAUTO in immune thrombocytopenia were 44.0% and 95.7%, respectively. The values of positive and negative predictions were 98.0% and 26.2%, respectively. Among those PAKAUTO positive patients, positive rates of GPIIb/IIIa, GPIa/IIa and GPIb/IX were 87%, 35% and 10%, respectively. The positive rate of patients not received immune suppressive agents (58.5%) was significantly higher than those received immune suppressive agents (26.9%) (P < 0.01). The positive rate of patients with platelet count ≤ 20 × 10(9)/L (51.6%) was significantly higher than those with platelet count > 20 × 10(9)/L (27.8%) (P < 0.01). The positive rate of patients with secondary immune thrombocytopenia (66.7%) was significantly higher than those with primary immune thrombocytopenia (41.7%) (P < 0.05).</p><p><b>CONCLUSION</b>The highly specific method (PAKAUTO) could effectively differentiate immune or non-immune thrombocytopenia and be applied to diagnosis of immune thrombocytopenia.</p>


Sujets)
Femelle , Humains , Mâle , Autoanticorps , Allergie et immunologie , Test ELISA , Méthodes , Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire , Allergie et immunologie , Complexe glycoprotéique GPIb-IX plaquettaire , Allergie et immunologie , Glycoprotéines de membrane plaquettaire , Allergie et immunologie , Sensibilité et spécificité , Thrombopénie , Diagnostic , Allergie et immunologie
6.
Chinese Journal of Hematology ; (12): 583-586, 2011.
Article Dans Chinois | WPRIM | ID: wpr-251521

Résumé

<p><b>OBJECTIVE</b>To compare the efficacy of two different regimens of low doses rituximab for the treatment of adult patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Fifty-one patients were enrolled in this study and was non-randomly assigned to receive 100 mg rituximab weekly for 4 weeks (group A, 31 cases) or a single dose of 375 mg/m2 rituximab (group B, 20 cases).</p><p><b>RESULTS</b>For group A: Overall and complete response (OR and CR) rates were 58% and 29% , respectively. In responders, the median time to response was 42 (10 -101) days, with a median follow-up time of 15 (10 - 16) months, 3 of 18 responders (17%) relapsed. For group B: OR and CR rates were 50% and 35% , respectively. In responders, the median time to response was 35 (18 - 108) days, with a median follow-up time of 13 (6 -17) months, 1 of 9 responders (11%) relapsed. No significant difference in the OR, CR, the relapse rate and relapse free survival was observed in patients between the two groups.</p><p><b>CONCLUSION</b>The low dose rituximab regimen (100 mg weekly for 4 weeks or a single close of 375 mg/m2) may be a useful alternative therapy in patients with ITP.</p>


Sujets)
Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Anticorps monoclonaux , Utilisations thérapeutiques , Anticorps monoclonaux d'origine murine , Utilisations thérapeutiques , Relation dose-effet des médicaments , Rituximab , Thrombopénie , Traitement médicamenteux , Résultat thérapeutique
7.
Chinese Journal of Hematology ; (12): 592-596, 2011.
Article Dans Chinois | WPRIM | ID: wpr-251519

Résumé

<p><b>OBJECTIVE</b>To investigate the role of Th17 cells in immune thrombocytopenia (ITP) mice model.</p><p><b>METHOD</b>ITP was induced by daily intraperitoneal injection of anti-platelet membrane CD41 antibody (MWReg30) into BALB/c mice, the mRNA expressions of Th17 cell associated transcription factors and cytokines in peripheral blood and spleen mononuclear cells were measured by real-time PCR, and the proportion of Th17 cells by FCM analysis.</p><p><b>RESULTS</b>The percentage of Th17 cell was significantly elevated in ITP mice both in splenocyte and peripheral blood as compared with that in normal controls (P<0.01). ITP mice had elevated mRNA expressions of IL-17F, IL-17A and IL-6 in splenocyte (P<0.05), and of IL-21 in peripheral blood (P<0.05). There was a positive correlation between IL-17A and IL-17F (r = 0.934, P = 0.000), and between IL-17A/IL-17F and IL-6 (r = 0.598, P = 0.001; r = 0. 619, P = 0.000).</p><p><b>CONCLUSIONS</b>Th17 cell might play an important role in the pathogenesis of ITP, at least involving in the clearance of platelets.</p>


Sujets)
Animaux , Femelle , Souris , Modèles animaux de maladie humaine , Souris de lignée BALB C , Cellules Th17 , Allergie et immunologie , Thrombopénie , Allergie et immunologie
8.
Chinese Journal of Hematology ; (12): 577-580, 2010.
Article Dans Chinois | WPRIM | ID: wpr-353614

Résumé

<p><b>OBJECTIVE</b>To explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient.</p><p><b>METHODS</b>The FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR.</p><p><b>RESULTS</b>FVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months.</p><p><b>CONCLUSION</b>This is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.</p>


Sujets)
Humains , Autoanticorps , Allergie et immunologie , Facteur VIII , Génétique , Hémophilie A , Génétique , Tolérance immunitaire , Immunosuppression thérapeutique
9.
Journal of Experimental Hematology ; (6): 184-187, 2009.
Article Dans Chinois | WPRIM | ID: wpr-302170

Résumé

The purpose of this study was to investigate the expression of human Factor IX (hFIX) in retrovirus-transfected human umbilical cord tissue derived mesenchymal stem cells (hUCT-MSCs). The pLEGFP-N1-hFIX vector was generated by cloning a 3.0 kb Bgl II-BamH I fragment from the pIRES2-EGFP-hFIX plasmid containing the hFIX cDNA and part of intron 1 of hFIX in pLEGFP-N1 vector. The retroviral supernatants were produced from the Phoenix packaging cell line and then infected the hUCT-MSCs. After selection with G418 for 10 day, the expression of FIX was detected by ELISA and Western blot. The biological activity of FIX was determined by the clotting assay employing human Factor IX-deficient plasma. The results showed that compared with the activity of pooled human normal plasma (100%), transduced cells produced biologically active hFIX with 100-130% activity in two-day culture supernatant and expressed hFIX at levels of 2.68 +/- 0.36 microg/10(6) cells/24 hours after G418 selection for 10 days. The secretion of hFIX into culture supernatant was also confirmed by Western blot analysis. It is concluded that genetically modified hUCT-MSCs can express biologically active hFIX and thus serve as an efficient drug delivery vehicle carrying hFIX used as a way of somatic gene therapy for hemophilia B.


Sujets)
Humains , Lignée cellulaire , Facteur IX , Génétique , Expression des gènes , Thérapie génétique , Vecteurs génétiques , Cellules souches mésenchymateuses , Retroviridae , Génétique , Transfection
10.
Journal of Experimental Hematology ; (6): 266-270, 2009.
Article Dans Chinois | WPRIM | ID: wpr-302151

Résumé

Bmi-1 is a transcriptional repressor, which belongs to the polycomb group family. It has been demon- started that over-expression of Bmi-1 occurs in a variety of cancers, including several types of leukemia. Bmi-1 gene plays a key role in regulation of self-renewal in normal and leukemic stem cells. Acute myeloid leukemic cells lacking Bmi-1 undergo proliferation arrest and show signs of differentiation and apoptosis, which leads to the proposal of Bmi-1 as a potential target for therapeutic intervention in leukemia. The purpose of this study was to investigate the effect of short hairpin RNA (shRNA) targeting Bmi-1 on functions of K562 cell line. The shRNA eukaryotic expression vector targeting Bmi-1 was constructed and transfected into K562 cells through lipofectamine 2000. The mRNA and protein levels of Bmi-1 were detected by PCR and Western blot respectively. The proliferation of K562 after Bmi-1 silencing was measured by using MTT assay and clone formation assay. The cell cycle was detected by flow cytometry. The results indicated that among the four shRNA designed, there was a shRNA which efficiently interfered with the expression of Bmi-1. The results of PCR and Western blot validated that the Bmi-1 gene of K562 cells transfected with such a Bmi-1 shRNA was suppressed successfully. Although levels of Bmi-1 mRNA and protein were significantly reduced, delivery of this siRNAs had no effect on cell viability or growth. Flow cytometry analysis suggested that Bmi-1 inhibition did not affect the cell cycle. It is concluded that the suppression of Bmi-1 expression is not able to reduce proliferation of K562 cells, suggesting existence of some other parallel signaling pathways, which are fundamental for leukemic transformation and are independent of Bmi-1 over-expression. Bmi-1 over-expression may play a secondary role in chronic myeloid leukemia transformation.


Sujets)
Humains , Prolifération cellulaire , Survie cellulaire , Vecteurs génétiques , Cellules K562 , Leucémie myéloïde chronique BCR-ABL positive , Génétique , Protéines nucléaires , Génétique , Complexe répresseur Polycomb-1 , Protéines proto-oncogènes , Génétique , Interférence par ARN , Petit ARN interférent , Génétique , Protéines de répression , Génétique , Transfection
11.
Journal of Experimental Hematology ; (6): 1372-1375, 2008.
Article Dans Chinois | WPRIM | ID: wpr-234231

Résumé

The study was aimed to investigate the potential immunotherapeutical values of umbilical cord tissue-derived mesenchymal stem cells (UC-MSC) on patients with chronic idiopathic thrombocytopenic purpura (ITP). UC-MSC was cocultured in vitro with splenocytes isolated from ITP patients who experienced splenectomy. The level of IgG antiplatelet antibody (PAIgG) was determined by a competitive micro-enzyme-linked immunosorbent assay (ELISA) method. The proliferation of platelet-reactive CD4+ T lymphocytes was also measured in the presence of UC-MSCs. The results showed that UC-MSCs could stimulate the spontaneous secretion of PAIgG in supernatants; In the platelet-inducing condition, UC-MSC inhibited the production of PAIgG at a low ratio of 1 UC-MSC to 100 splenocytes, but promoted at a high proportion of 1 UC-MSC to 10 splenocytes. Moreover, UC-MSC exerted a suppressive effect on proliferation of platelet-reactive T helper cells in a dose-dependent manner. It is concluded that the UC-MSCs can regulate secretion of antiplatelet antibodies in vitro. Its concrete regulation mechanism and potential immunotherapeutical value are need to further study.


Sujets)
Humains , Nouveau-né , Anticorps , Métabolisme , Plaquettes , Allergie et immunologie , Lymphocytes T CD4+ , Biologie cellulaire , Prolifération cellulaire , Activation des lymphocytes , Cellules souches mésenchymateuses , Physiologie , Purpura thrombopénique idiopathique , Métabolisme , Rate , Biologie cellulaire , Cordon ombilical , Physiologie
12.
Chinese Journal of Hematology ; (12): 327-329, 2007.
Article Dans Chinois | WPRIM | ID: wpr-328354

Résumé

<p><b>OBJECTIVE</b>To report 7 cases of acquired hemoglobin H in myelodysplastic syndromes.</p><p><b>CASE DATA AND DISCUSSION</b>Clinical materials of the 7 cases were retrospectively presented. Clinical features of the similar cases in literatures were reviewed. The criteria for diagnosis of this entity by Steensma and its pathogenesis were discussed.</p><p><b>CONCLUSION</b>This entity is a new subtype of MDS with unique clinical features and pathogenesis, and might be a proper model in the study of MDS transformation.</p>


Sujets)
Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Syndromes myélodysplasiques , alpha-Thalassémie
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