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PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
Assuntos
Antineoplásicos , Arsênio , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/efeitos adversos , Arsênio/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pandemias , Resultado do TratamentoRESUMO
BACKGROUND: BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It can cause morbidity and may increase treatment-related mortality. Previous studies showed that the occurrence of BKV-HC was related to various factors. However, there are still many controversial factors. It is not clear whether BKV-HC will affect the long-term prognosis of patients. OBJECTIVE: We aimed to identify risk factors for BKV-HC after allo-HSCT and evaluate the effect of BKV-HC on overall survival (OS) and progression- free survival (PFS) of patients. STUDY DESIGN: We retrospectively analyzed the clinical data of 93 patients who underwent allo-HSCT. Univariate and multivariate analysis were used to identify risk factors for BKV-HC. The Kaplan-Meier method was used to estimate OS and PFS. A difference was considered statistically significant if P < 0.05. RESULTS: A total of 24 patients developed BKV-HC. The median occurrence time of BKV-HC was 30 (range:8-89) days after transplantation, and the median duration was 25.5 (range:6-50) days. Multivariate logistic regression analysis indicated that peripheral blood lymphocyte count <1 × 109/L before conditioning (OR = 4.705, P = 0.007) and haploidentical transplantation (OR = 13.161, P = 0.018) were independent risk factors for BKV-HC. The 3-year OS rate was 85.9% (95%CI:62.1%-95.2%) in the BKV-HC group and 73.1% (95%CI: 58.2%-88.0%) in the non-BKV-HC group. There was no significant difference between the two groups (P = 0.516). The 3-year PFS rate was 76.3% (95%CI: 57.9%-94.7%) in the BKV-HC group and 58.1% (95%CI: 39.5%-76.7%) in the non-BKV-HC group. There was no significant difference in the two groups (P = 0.459). The severity of BKV-HC was not related to the OS and PFS of the patients (P value was 0.816 and 0.501, respectively). CONCLUSION: Haploidentical transplantation and decreased peripheral blood lymphocyte count before conditioning increased the risk of BKV-HC after allo-HSCT. The occurrence of BKV-HC after allo-HSCT and the severity of which did not affect OS and PFS of the patients.
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Vírus BK , Cistite , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversosRESUMO
OBJECTIVE: This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells (CAR-T cells) versus chemotherapy plus donor lymphocyte infusion (chemo-DLI) for treating relapsed CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed. Twenty-two patients were treated with CAR-T cells (CAR-T group), and 21 with chemotherapy plus DLI (chemo-DLI group). The complete remission (CR) and minimal residual disease (MRD)-negative CR rates, leukemia-free survival (LFS) rate, overall survival (OS) rate, and incidence of acute graft-versus-host disease (aGVHD), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were compared between the two groups. RESULTS: The CR and MRD-negative CR rates in the CAR-T group (77.3% and 61.5%) were significantly higher than those in the chemo-DLI group (38.1% and 23.8%) (P=0.008 and P=0.003). The 1- and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group: 54.5% and 50.0% vs. 9.5% and 4.8% (P=0.0001 and P=0.00004). The 1- and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1% and 54.5% vs. 19% and 9.5% (P=0.011 and P=0.003). Six patients (28.6%) with grade 2-4 aGVHD were identified in the chemo-DLI group. Two patients (9.1%) in the CAR-T group developed grade 1-2 aGVHD. Nineteen patients (86.4%) developed CRS in the CAR-T group, comprising grade 1-2 CRS in 13 patients (59.1%) and grade 3 CRS in 6 patients (27.3%). Two patients (9.1%) developed grade 1-2 ICANS. CONCLUSION: Donor-derived anti-CD19 CAR-T-cell therapy may be better, safer, and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
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Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Linfócitos T , Humanos , Doença Aguda , Doença Crônica , Linfócitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Estudos Retrospectivos , Antígenos CD19RESUMO
Patients with relapsed/refractory hematologic malignancies after allogeneic stem cell transplantation have a poor prognosis due to the high rate of relapse. Techniques capable of decreasing post-transplantation relapse rates are urgently sought. This study aimed to explore the feasibility and safety of allogeneic hematopoietic stem cell transplantation (HSCT) following infusion of donor cytokine-induced killer (CIK) cells. CIK cells were generated in vitro from donor peripheral blood mononuclear cells, and were phenotyped using flow cytometric analysis. CIK cells were administered to 15 high-risk relapsed/refractory hematologic malignancy patients who were not in complete remission in multiple infusions. These patients also received allogeneic HSCT. The side effects and outcomes were recorded. All patients achieved engraftment and complete remission. After CIK cell infusion, two patients developed graft-versus-host disease (GvHD), which was controlled by additional immunosuppressant drugs. At the last follow-up, nine patients had died and six patients were surviving at a median follow-up of 1513days (range, 771-1655days). In conclusion, allogeneic HSCT combined with sequential infusion of donor CIK cells is well tolerated in salvage relapsed/refractory hematologic malignancy patients.
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Células Matadoras Induzidas por Citocinas/transplante , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Transfusão de Leucócitos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Terapia de Salvação/métodos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Ginsenoside Rg3 is one of the main constituents isolated from Panax ginseng, and exhibits cytotoxic effects against cancer cells. The present study aimed to investigate the effects of ginsenoside Rg3 on human multiple myeloma cells, and determine the underlying molecular mechanisms. The cells were exposed to ginsenoside Rg3 at various concentrations (080 µM) for 48 h. A subsequent cell proliferation assay demonstrated that treatment with ginsenoside Rg3 resulted in a dosedependent inhibition of the proliferation of U266 and RPMI8226 cells. Furthermore, exposure to ginsenoside Rg3 led to a marked increase in the rate of apoptosis in the U266 cells, coupled with increased caspase3 activity. The ginsenoside Rg3treated cells also exhibited an elevation in the expression of Bcell lymphoma 2associated X protein (Bax), a proapoptotic protein. Notably, knockdown of Bax protected the U266 cells from Rg3induced apoptosis. Overall, these findings suggested that ginsenoside Rg3 induced apoptosis in multiple myeloma cells, at least partially, through upregulation of the expression of Bax.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Ginsenosídeos/química , Humanos , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Panax/químicaRESUMO
We present a 56-year-old woman with bilateral pleural effusions, widespread enlarged lymph nodes, and soft tissue masses located within the renal pelvis. The initially working diagnosis was tuberculosis and lymphoma. Further pathological examination of the lymph node biopsy confirmed a diagnosis of extramedullary hematopoiesis, and a bone marrow biopsy revealed myelofibrosis. Unlike common treatment options such as radiotherapy and/or surgery, intrathoracic cisplatin and dexamethasone for the treatment of pleural effusions secondary to extramedullary hematopoiesis demonstrated an improvement in feasibility and efficacy in the present case.
RESUMO
To investigate the feasibility of using focused ultrasound (FUS) with microbubbles for targeted delivery of cytarabine to the brain. Sprague-Dawly rats (weighing 200-250 g) received focused ultrasound with intravenous injection microbubbles. At 0, 2, 4, 8, and 24 hours (n=5 for each time point) after sonication, animals received intravenous administration of cytarabine at a normal dose of 4 mg/kg body weight. Additional five rats were given with a high dose (50 mg/kg body weight) of cytarabine alone. Blood-brain barrier (BBB) permeability and cerebral cytarabine were determined. FUS in conjunction with microbubbles caused a transient BBB opening. Sonication exposure promoted cytarabine accumulation at the sonicated site. Animals injected with a normal dose of cytarabine 2 hours after sonication had similar concentrations of cerebral cytarabine compared to those with higher cytarabine without sonication. FUS can temporarily open the BBB and thus facilitate the penetration of systemic cytarabine into the brain.
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Antimetabólitos Antineoplásicos/farmacocinética , Barreira Hematoencefálica/efeitos da radiação , Córtex Cerebral/metabolismo , Citarabina/farmacocinética , Sistemas de Liberação de Medicamentos , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/análise , Barreira Hematoencefálica/metabolismo , Córtex Cerebral/citologia , Meios de Contraste , Citarabina/administração & dosagem , Citarabina/análise , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Injeções Intravenosas , Imageamento por Ressonância Magnética , Masculino , Microbolhas , Permeabilidade , Projetos Piloto , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Ultrassom/métodosRESUMO
AIM: to construct a eukaryolic expression plasmid of Ppic9k-IL3-Linker-PE38KDE. METHODS: the IL3 and PE38KDEL gene were amplified by polymerase chain reaction (PCR) and cloned into the eukaryolic expression plasmid Ppic9k-Linker constructed after being sequenced.The recombinant vector confirmed by restriction endonucleases digestion, coenobium PCR and DNA sequence analysis showed that the prokaryotic expression vector Ppic9k-IL3-Linker-PE38KDEL was constructed successfully. CONCLUSION: the fusion gene IL3-PE38KDEL is successfully constructed, which laid a solid foundation for the further research.
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Vetores Genéticos/síntese química , Imunotoxinas/química , Interleucina-3/genética , Pichia/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Biomarcadores Tumorais/química , Biomarcadores Tumorais/genética , Clonagem Molecular/métodos , Vetores Genéticos/química , Vetores Genéticos/genética , Humanos , Imunotoxinas/imunologia , Interleucina-3/biossíntese , Interleucina-3/química , Leucemia/patologia , Leucemia/terapia , Pichia/metabolismo , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA/métodosRESUMO
OBJECTIVE: To describe the demographic and clinical characteristics of patients with the diagnosis of multiple myeloma (MM) and to analyse the outcome of different regimens for the treatment of MM. METHODS: The study reviewed 332 MM cases diagnosed within the period from January 1, 2002 to December 31, 2002. These patients were tracked via their records to a total period of three years. RESULTS: First-line treatment: Totally 332 patients were included, among them 325 (97.9%) patients received chemotherapy and 7 (2.1%) patients received stem cell transplantation (SCT); Second-line treatment: 197 patients were included, among them 190 (96.5%) patients received chemotherapy and 7 (3.6%) patients received SCT; Third-line treatment: 92 patients were included,among them 88 (95.7%) patients received chemotherapy and 4 (4.4%) patients received SCT. Major adverse effects were follows: severe infection 19.3%, severe anaemia 19.3%, phlebothrombosis 1.2% , thrombocytopenia 16.9%, fever associated with neutropenia 18.1%. CONCLUSIONS: Some curative effects can be achieved by using traditional treatment plans to treat patients suffering from MM, but new methods are expected to improve the prognosis.
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Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Tratamento Farmacológico/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Febre/etiologia , Humanos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/estatística & dados numéricos , Análise de Sobrevida , Trombocitopenia/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the therapeutic efficacy of 131I-labeled granulocyte macrophage colony-stimulating factor (GM-SCF) in SCID mouse-acute myeloid leukemia model, and the relationship between dose and effect. METHODS: SCID-mouse acute myeloid leukemia model was established by injecting HL-60 cells through tail vein. GM-CSF was labeled with 131I by the chloramines-T method. SCID mice were randomly divided into 6 groups. Groups I, II and III treatment groups were given 9.25 x 10(5), 22.20 x 10(5) and 37.00 x 10(5) Bq of 131I-GM-CSF, respectively. Group IV was given 131I. Group V was given blending of 131I and GM-CSF. Group VI was control. Changes of HL-60 cells in blood and marrow, as well as white blood cells, red blood cells and platelets in blood were detected. Survival time of the SCID mice was calculated. RESULT: It was observed that WBC, HL-60 cells in blood and marrow were less in treatment groups than that in control groups, especially in groups II, III. After 2 weeks of treatment, BPC of II, III groups increased remarkably (P < 0.01). Survival time of the SCID mice was prolonged in treatment groups (P < 0.01), especially in group III, the longest survival time of 60 days. CONCLUSION: 131I-GM-CSF could increase leukemic SCID mice survival rate. The therapeutic efficacy of low dose and mediate dose of 131I-GM-CSF is dose-dependent. 131I-GM-CSF is an effective radiation immunity therapy for leukemic mice.
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Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Feminino , Células HL-60 , Humanos , Camundongos , Camundongos SCID , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the biodistribution of 131I-GM-CSF in SCID mice bearing human AML in vivo. METHODS: The xenograft model of human leukemia was established in SCID mice. In the leukemia mice, the biodistribution of 131I-GM-CSF produced by chlo amine-T method was studied. RESULTS: (1)The inoculated HL-60 cells could grow in SCID mice, which developed leukemia after 4 weeks. (2) 131 I-GM-CSF was concentrated in spleen, bone marrow and tumor tissue of the mice. In spleen and bone marrow, 131 I-GM-CSF was uptaken to peak in 30 minutes after injection, the up taking rate was (442. 9+/-86. 4) % ID/g and (4283. 8+/-252. 8)% ID/g, respectively, and maintained on higher level in 24 hours. The injection of 131I resulted in an even distribution in the whole body. CONCLUSIONS: 131 I-GM-CSF is able to concentrate electively in spleen, bone marrow and organs infiltrated by leukemia cells. The biodistribution of 131I-GM-CSF in the leukemia mice is tissue specific.