RESUMO
OBJECTIVE: To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion for the treatment of aplastic anaemia in children. METHODS: Nine cases of children with aplastic anaemia treated with umbilical cord blood combined with haploidentical hematopoietic stem cell transplantation at the People's Hospital of Henan University of Chinese Medicine from January 1, 2021 to September 15, 2023 with a median age of 11(2-13) years and a median follow up of 18(7.5-21) months were included, and the clinical data were retrospectively analyzed. Hematopoiesis reconstitution, the incidence of graft-versus-host disease(GVHD), infections and survival of the patients were analyzed. RESULTS: All 9 children were successfully implanted. The median time to neutrophil and platelet implantation was 11.11±1.27 d and 12.44±3.36 d, respectively. One case developed acute gastrointestinal GVHD of degree I, which was improved after treatment, and the patient developed superficial gastritis and chronic gastrointestinal GVHD at a later stage, which is currently under clinical follow-up. Acute GVHD of II-IV degree was 0%. Hemorrhagic cystitis in 3 cases, CMV infection in 5 cases and bacterial and fungal infections in 5 cases improved with symptomatic treatment.All 9 children demonstrated complete donor chimerism within 1 month after transplantation, at two years of follow-up, all nine children survived without recurrence or development of grade II-IV GVHD, and there were no children with transplant-related deaths. CONCLUSION: Haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood transfusion for aplastic anaemia in children has a low incidence and mild degree of GVHD, with significant efficacy, and can be used as a therapeutic option for children without an HLA full donor chimeric match.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Anemia Aplástica/terapia , Criança , Pré-Escolar , Estudos Retrospectivos , Adolescente , Sangue Fetal , Transplante Haploidêntico , Masculino , FemininoRESUMO
BACKGROUND: In critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial. METHODS: Clinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed. RESULTS: A total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876-0.919), and 0.896 (95% CI: 0.866-0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups. CONCLUSION: The prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.
Assuntos
Estado Terminal , Respiração Artificial , Traqueotomia , Humanos , Traqueotomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Respiração Artificial/métodos , Fatores de Tempo , Unidades de Terapia Intensiva , Escala de Coma de Glasgow , Valor Preditivo dos Testes , Curva ROCRESUMO
INTRODUCTION: In recent years, with the development of molecular epidemiology, molecular transmission networks based on evolutionary theory and sequence analysis have been widely used in research on human immunodeficiency virus (HIV)-1 transmission dynamics and precise intervention for high-risk populations. The HIV-1 molecular transmission network is a new method to study the population's access to the network, the characteristics of clustering, and the characteristics of interconnection in the network. Here, we analyzed the characteristics of the HIV-1 molecular transmission network of sexually transmitted people in Liaoning Province. METHODS: A study of HIV-infected persons who were sexually transmitted in Liaoning Province from 2003 to 2019. HIV-1 RNA was extracted, amplified and sequenced, and a phylogenetic tree was constructed to determine the subtype using the well matched pol gene region sequence. The gene distance between sequences was calculated, the threshold was determined, and the molecular transmission network was constructed. RESULTS: 109 samples of pol gene region were obtained. The main subtype of HIV-1 was CRF01_AE, followed by B, CRF07_BC, etc. 12.8% of them were resistant to HIV. At the threshold of 0.55 gene distance, 60.6% of them entered the HIV-1 molecular transmission network. Workers, sample source voluntary counseling and testing, other testing, subtype B and drug resistance are the factors influencing the access to HIV-1 molecular transmission network. The subtype of CRF01_AE formed 6 clusters in the molecular transmission network. In the network, the difference of connection degree between different subtypes was statistically significant. DISCUSSION: The three subtypes CRF01_AE, CRF07_BC and B that enter the molecular transmission network do not have interconnections, and they form clusters with each other. It shows that the risk of transmission among the three subtypes is less than the risk of transmission within each subtype. The factors affecting HIV-1 entry into the molecular transmission network were occupation, sample source, genotype and drug resistance. The L33F mutation at the HIV-1 resistance mutation site constitutes the interconnection in the largest transmission cluster in the network. The epidemiological characteristics of HIV-infected persons in each molecular transmission cluster show that 97% of the study subjects come from the same area and have a certain spatial aggregation. CONCLUSION: Constructing a molecular transmission network and conducting long-term monitoring, while taking targeted measures to block the spread of HIV can achieve precise prevention and control.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/genética , HIV-1/genética , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/genética , Adulto , China/epidemiologia , Feminino , Genótipo , Infecções por HIV/etnologia , Infecções por HIV/transmissão , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , RNA Viral , Análise de Sequência de DNA , Doenças Virais Sexualmente Transmissíveis/etnologia , Fatores SocioeconômicosAssuntos
Rearranjo Gênico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Promielocítica Aguda/diagnóstico , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Receptores do Ácido Retinoico/genética , Receptores X de Retinoides/genética , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/genética , Pessoa de Meia-Idade , Prognóstico , Receptor gama de Ácido RetinoicoRESUMO
OBJECTIVE: To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. METHODS: A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. RESULTS: Significant differences in 11 factors (age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum ß2-microglobulin) were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index (IPI), revised IPI, and NCCN-IPI models] (P < 0.05). Concordance rates were high (81.4%-100.0%) when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. CONCLUSION: We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.
Assuntos
Linfoma de Células B/classificação , Linfoma de Células B/patologia , Adulto , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8. Additionally, quantitative polymerase chain reaction and flow cytometry were used to detect the expression of the associated genes and proteins. The present study explores the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study showed that hBMSCs promoted the proliferation of TKI-resistant Ph+ ALL. This was shown by the increase in cells in the S+G2-M phase of the cell cycle. It was also found that the expression of cyclins A, C, D1 and E was increased. Apoptosis was inhibited through upregulation of anti-apoptotic genes [B-cell lymphoma-2 (BCL-2) and BCL-extra large] and downregulation of apoptotic genes (BCL-XS, BCL-2-associated X protein, and caspases 3, 7 and 9). Expression of the breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL) gene, Wnt5a, and Wnt signaling pathway-associated genes (glycogen synthase kinase-3ß, ß-catenin, E-cadherin and phosphoinositide 3-kinase) and transcription factors (c-myc, ephrin type-B2, fibroblast growth factor 20 and matrix metalloproteinase 7) was also increased. Furthermore, the expression of drug resistance genes (low-density lipoprotein receptor, multidrug resistance-associated protein and multi-drug resistance gene) was increased and the expression of anti-oncogenes (death-associated protein kinase and interferon regulatory factor-1) was decreased. It was concluded that hBMSCs promote the growth of TKI-resistant Ph+ ALL by these aforementioned mechanisms. Therefore, targeting hBMSCs may be a promising approach for preventing the growth of TKI-resistant Ph+ ALL.
RESUMO
Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and (-)-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years. To investigate the anti-tumor effect of valproic acid and (-)-gossypol, Burkitt lymphoma Namalwa cells were cultured and treated with valproic acid and (-)-gossypol at different concentrations. The proliferation of Namalwa cells was dramatically suppressed after the combination treatment with 2 mmol/L valproic acid and 5 µmol/L (-)-gossypol. The combined treatment also enhanced intrinsic apoptosis by down-regulating anti-apoptotic protein Mcl-1. Moreover, the autophagy flux significantly increased in Namalwa cells after combined treatment. However, the enhanced autophagy showed little effect on cell survival with present regimen. The results confirmed that combination of valproic acid and (-)-gossypol had synergistic anti-tumor effect to Burkitt lymphoma Namalwa cells. The related mechanisms might include the down-regulation of anti-apoptotic protein Mcl-1 and avianized pro-survival role of autophagy.
Assuntos
Linfoma de Burkitt/tratamento farmacológico , Gossipol/farmacocinética , Ácido Valproico/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Anticoncepcionais Masculinos/administração & dosagem , Anticoncepcionais Masculinos/farmacocinética , Anticoncepcionais Masculinos/uso terapêutico , Sinergismo Farmacológico , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Gossipol/administração & dosagem , Gossipol/uso terapêutico , Humanos , Ácido Valproico/administração & dosagem , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined. METHODS: Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP). RESULTS: ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment. CONCLUSIONS: ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.
Assuntos
Comunicação Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Conexina 43/genética , Junções Comunicantes/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Tretinoína/farmacologia , Doença Aguda , Adulto , Anfotericina B/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Comunicação Celular/genética , Pontos de Checagem do Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Conexina 43/metabolismo , Feminino , Recuperação de Fluorescência Após Fotodegradação , Junções Comunicantes/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Corticosteroid therapy followed by splenectomy for immune thrombocytopenic purpura (ITP) is the standard practice. Rituximab is mostly used in patients with chronic refractory ITP who have failed multiple previous treatments, including splenectomy. OBJECTIVE: We explored the potential role of rituximab as an early therapeutic option for patients with corticosteroid-resistant ITP who preferred to avoid splenectomy in favor of other treatment. METHODS: Twenty-five patients with corticosteroid-resistant ITP were treated with rituximab between May 1, 2009, and June 30, 2012, at a single center. Rituximab was administered at 100 mg/m(2) on days 7, 14, 21, and 28. The response to rituximab therapy and adverse effects were observed. RESULTS: Complete remission was achieved in 19 patients (76%), partial remission in 3 patients (12%), and minimal response in none of the patients; 1 patient was considered a treatment failure (4%). Two patients (8%) were lost to follow-up. Twenty-two patients (88%) achieved a platelet count >50 × 10(9)/L. The median time from administration of the first rituximab dose to partial remission was 2 months (range, 0.7-3 months) for all the patients. Response classified as sustained was achieved in 21 patients (84%). No serious adverse effects were observed during rituximab therapy. CONCLUSIONS: Rituximab therapy is effective and safe for patients with corticosteroid-resistant ITP before splenectomy, resulting in high complete remission and overall response rates. A multicenter study with a larger sample should be performed to further explore the role of rituximab therapy.
Assuntos
Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Idoso , Antígenos CD20/imunologia , Criança , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/cirurgia , Indução de Remissão , Esplenectomia , Falha de TratamentoRESUMO
Interleukin-6 (IL-6) is a proinflammatory cytokine that is multifunctional, with multifaceted effects. IL-6 signaling plays a vital role in the control of the differentiation and activation of T lymphocytes by inducing different pathways. In particular, IL-6 controls the balance between Th17 cells and regulatory T (Treg) cells. An imbalance between Treg and Th17 cells is thought to play a pathological role in various immune-mediated diseases. Deregulated IL-6 production and signaling are associated with immune tolerance. Therefore, methods of inhibiting IL-6 production, receptors, and signaling pathways are strategies that are currently being widely pursued to develop novel therapies that induce immune tolerance. This survey aims to provide an updated account of why IL-6 inhibitors are becoming a vital class of drugs that are potentially useful for inducing immune tolerance as a treatment for autoimmune diseases and transplant rejection. In addition, we discuss the effect of targeting IL-6 in recent experimental and clinical studies on autoimmune diseases and transplant rejection.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Autoimunidade/genética , Tolerância Imunológica/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Interleucina-6/imunologia , Receptores de Interleucina-6/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Diferenciação Celular , Regulação da Expressão Gênica/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Ativação Linfocitária , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/genética , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologiaRESUMO
The hematopoietic inductive microenvironment (HIM), which is composed of stromal cells, extracellular matrix and cytokines, plays a vital role in hematopoietic stem cell transplantation (HSCT). Bone marrow stromal cells (BMSCs), as the main component of HIM, have been well studied. However, the highly invasive procedure of bone marrow (BM) collection limits the clinical application of BMSCs. Human umbilical cord blood-derived stromal cells (hUCBDSCs) isolated and cultured in our laboratory have attracted much attention for their ease collection and low probability of pathophoresis. Previous research demonstrated that hUCBDSCs have numerous functions that are identical to those of BMSCs, for example, hUCBDSCs can support the growth of hematopoietic stem and progenitor cells, especially during the expansion of megakaryocyte colony-forming units (CFU-Mk), promote engraftment after hematopoietic stem cell transplantation (HSCT), exert immunosuppressive effects on xenogenic T cells in vitro and suppress acute graft-versus-host disease (aGVHD) in vivo. Although hUCBDSCs, as new stromal cells, have not been used in clinical practice, they have great practical significance because of their superiority in hematopoiesis and the regulation of immunity.
Assuntos
Sangue Fetal/citologia , Transplante de Células-Tronco Hematopoéticas , Células Estromais/citologia , Humanos , Células Estromais/transplanteRESUMO
BACKGROUND/OBJECTIVE: Bone marrow stromal cells (BMSCs) can support multiple myeloma (MM) disease progression and resistance to chemotherapy. The proliferation of MM cells may be suppressed by modifying the hematopoietic microenvironment (HME). We have previously isolated human umbilical cord blood-derived stromal cells (hUCBDSCs) and observed that hUCBDSCs suppressed proliferation and induced apoptosis in KM3 cells. To examine the mechanism by which hUCBDSCs drive the inhibition of MM, KM3 cells were co-cultured with hUCBDSCs. METHODS: Interleukin (IL)-6 and soluble IL-6 receptor (sIL-6R) expression levels were measured by enzyme-linked immunosorbent assay. The expression levels of membrane IL-6 receptor (mIL-6R), intercellular cell adhesion molecule-1 (ICAM-1), B-cell lymphoma/leukemia-2 (Bcl-2), and Bcl-XL as well as the location of nuclear factor κB (NF-κB) were assessed by laser confocal microscopy. The expression profiles of mIL-6R and ICAM-1 were also more precisely examined by flow cytometry, and Bcl-2, Bcl-XL and inhibitor kappa B expression levels were analyzed by western blot. The mRNA expression levels of IL-6R, ICAM-1, Bcl-2, and Bcl-XL were assessed by real-time polymerase chain reaction. NF-κB DNA-binding activity was examined by electrophoretic mobility shift assay. RESULTS: The protein expression levels of both sIL-6R and mIL-6R were reduced in culture conditions when KM3 cells were co-cultured with hUCBDSCs; moreover, the mRNA expression levels of IL-6R were also reduced. Nuclear translocation of the NF-κB p65 subunit was inhibited in KM3 cells by co-culture with hUCBDSCs. Moreover, hUCBDSCs inhibited NF-κB DNA-binding activity, thereby resulting in the downregulation of NF-κB-regulated proteins. CONCLUSION: hUCBDSCs can suppress proliferation and induce apoptosis in KM3 cells by both downregulating IL-6R expression and inhibiting NF-κB activity.
Assuntos
Apoptose , Proliferação de Células , Sangue Fetal/citologia , Células Estromais/citologia , Transporte Ativo do Núcleo Celular , Western Blotting , Núcleo Celular/metabolismo , Células Cultivadas , Técnicas de Cocultura , Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Microscopia Confocal , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
BACKGROUND: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a promising approach for non-Hodgkin's lymphoma (NHL). Higher cell doses have been associated with a faster blood count recovery and a reduction in transfusion requirements, infection rates, and hospitalization times. Mobilization failure constitutes one of the main reasons for avoiding auto-HSCT. The role of high-dose methotrexate (MTX) as mobilization regimen is still unclear. STUDY DESIGN AND METHODS: The effect of high-dose MTX as a mobilization regimen for 67 adult patients with NHL who received auto-HSCT was studied between January 2001 and October 2012. The stem cells were mobilized using combination chemotherapy including MTX plus granulocyte-colony-stimulating factor (G-CSF) in 33 patients (Group A), and the stem cells of the other 34 patients were mobilized using the same combination chemotherapy plus G-CSF without MTX (Group B). RESULTS: All of the patients were successfully mobilized in Group A; however, two patients failed in Group B. The median numbers of CD34+ cells collected were 14.36 × 10(6) and 5.3 × 10(6) cells/kg for Groups A and B, respectively (p < 0.05). All of the patients experienced a stable neutrophil and platelet (PLT) engraftment. The times to white blood cell engraftment were 8.0 days in Group A and 11.0 days in Group B, and the times to PLT engraftment were 12.0 days in Group A and 13.0 days in Group B (p < 0.05 for both variables). CONCLUSION: High-dose MTX is a powerful regimen component for stem cell mobilization in adult patients with NHL.
Assuntos
Mobilização de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Metotrexato/farmacologia , Adolescente , Adulto , Idoso , Feminino , Hematopoese , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma não Hodgkin/sangue , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/fisiologiaRESUMO
Regardless of the salvage therapy used, primary induction failure in acute lymphoblastic leukemia (refractory ALL) and relapse after a complete remission (CR) are associated with dismal outcomes. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be the best treatment option for relapsed/refractory ALL. However, the outcome of allo-HSCT is very poor when a patient is not in CR. Quiescent leukemia cells protect them from the commonly used cell cycle-specific chemotherapeutic agents. Interleukin-2 (IL-2), a very well characterized T cell growth factor, is responsible for the progression of T lymphocytes from the G0 to the S phase of the cell cycle. IL-2 receptors are present on malignant T cells. Interaction of IL-2 with the IL-2 receptor triggers T cell proliferation, but T cells must change from a resting to an activated state, which leads to the de novo synthesis of IL-2 and expression of the IL-2 receptor. Thus, exogenous IL-2 administration is pivotal for the activation of T cells. Based on the findings above mentioned, we hypothesized that IL-2 priming chemotherapy improves the remission of refractory/relapsed T cell acute lymphoblastic leukemia.
Assuntos
Interleucina-2/metabolismo , Modelos Biológicos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Indução de Remissão/métodos , Prevenção Secundária , Ciclo Celular/fisiologia , Humanos , Linfócitos T/citologiaRESUMO
We retrospectively analyzed allogenic stem cell transplantation (allo-SCT) outcomes in 82 patients with AML or MDS were conditioned with fludarabine, idarubicin, intravenous-busulfan and cytarabine (FIBA) or busulfan and cyclophosphamide (BuCy). Compared to BuCy regimen, reduced intensity conditioning (RIC) with FIBA was associated with a lower incidence of severe acute GVHD, lower NRM and a similar relapse rate. There was no significant difference in the 3 year overall survival (OS), but this is possibly due to the limited number of patients. The FIBA regimen is promising to replace BuCy regimen because of better security and similar relapse rate.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Citarabina/administração & dosagem , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/mortalidade , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto JovemRESUMO
Mixed-lineage acute leukemia (MAL) is characterized as acute leukemia involving acute myeloid cells and lymphoid cells at the same time. It is easily misdiagnosed because of the dual characteristics involving both lymphoid and myeloid cells and has a poor prognosis. We retrospectively analyzed the features and treatment effectiveness in a single center in 40 patients with MAL. The morphology was consistent with acute lymphoblastic leukemia (ALL) (47.5%) or acute myeloid leukemia (AML) (20%) or was inconclusive (32.5%). Twenty-two patients were characterized as B/myeloid, and 18 patients as T/myeloid. Cytogenetics showed t(9;22)/(Ph(+)) (12.5%) and 11q23/MLL rearrangements (6.25%). The rate of first complete remission for patients undergoing chemotherapy based on the features of both ALL and AML and of either ALL or AML was 71.4 and 42.9%, respectively. The 1-year overall survival rates were 37.5 and 60.0% for chemotherapy and chemotherapy followed by haploidentical hematopoietic stem cell transplantation (HSCT), respectively. The 1-year disease-free survival rates were 25.0 and 50.0% for chemotherapy and chemotherapy followed by HSCT, respectively. These results showed that MAL is confirmed to be a poor-risk disease. The chemotherapy for remission induction should be based on both myeloid cells and lymphoid cells. Transplantation should be performed after the first remission.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/cirurgia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto JovemRESUMO
Despite improvements in transplant immunology and clinical and supportive care, acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major cause of morbidity and mortality for patients after allogeneic hematopoietic stem cell transplantation (HSCT). Many ways have been used to prevent and treat aGVHD, however, long-term survival remains poor. The key to improve aGVHD outcomes may, in fact, rest upon successful initial therapy. The HLA-matched HSCT was limited by the shortage of suitable donors. Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells and G-CSF-mobilized bone marrow as a stronger aGVHD inhibition and graft-versus-leukemia effect, has been developed as an alternative transplantation strategy for patients with hematologic malignancies for the advantage of immediate donor availability, ability to select the best of many relatives, controlled graft composition and immediate access to donor-derived cellular therapies if required after transplantation. G-CSF is a potent hematopoietic cytokine, which is produced by fibroblasts, monocytes, and endothelial cells. G-CSF regulates production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, maturation and is also involved in mobilization of granulocytes, stem and progenitor cells, which has an important role in this transplantation. In this article, we review the possible mechanism for this combined G-CSF-mobilized HSCT in the prevention of aGVHD. Monocytes, T cells, Tregs cells, DC, adhesive molecule, NK cell/KIR ligand mismatching and mesenchymal stem cells may be involved in this transplantation.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Neoplasias Hematológicas/imunologia , Humanos , Transplante HomólogoRESUMO
The hematopoietic inductive microenvironment (HIM) is where hematopoietic stem/progenitor cells grow and develop. Hematopoietic stromal cells were the key components of the HIM. In our previous study, we had successfully cultured and isolated human cord blood-derived stromal cells (HUCBSCs) and demonstrated that they could secret hemopoietic growth factors such as GM-CSF, TPO, and SCF. However, it is still controversial whether HUCBSCs can be used for reconstruction of HIM. In this study, we first established a co-culture system of HUCBSCs and cord blood CD34(+) cells and then determined that using HUCBSCs as the adherent layer had significantly more newly formed colonies of each hematopoietic lineage than the control group, indicating that HUCBSCs had the ability to promote the proliferation of hematopoietic stem cells/progenitor cells. Furthermore, the number of colonies was significantly higher in vascular cell adhesion molecule-1 (VCAM-1)-modified HUCBSCs, suggesting that the ability of HUCBSCs in promoting the proliferation of hematopoietic stem cells/progenitor cells was further enhanced after having been modified with VCAM-1. Next, HUCBSCs were infused into a radiation-damaged animal model, in which the recovery of hematopoiesis was observed. The results demonstrate that the transplanted HUCBSCs were "homed in" to bone marrow and played roles in promoting the recovery of irradiation-induced hematopoietic damage and repairing HIM. Compared with the control group, the HUCBSC group had significantly superior effectiveness in terms of the recovery time for hemogram and myelogram, CFU-F, CFU-GM, BFU-E, and CFU-Meg. Such differences were even more significant in VCAM-1-modified HUCBSCs group. We suggest that HUCBSCs are able to restore the functions of HIM and promote the recovery of radiation-induced hematopoietic damage. VCAM-1 plays an important role in supporting the repair of HIM damage.