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1.
Ann Hematol ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637333

RESUMO

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

2.
Eur J Haematol ; 112(2): 257-265, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37698159

RESUMO

OBJECTIVES: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. RESULTS: The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. CONCLUSIONS: Thromboelastography was considered to be a good predictor of bleeding severity.


Assuntos
Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Humanos , Tromboelastografia , Imunoterapia Adotiva/efeitos adversos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/terapia , Terapia Baseada em Transplante de Células e Tecidos
3.
BMC Cancer ; 23(1): 1055, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919691

RESUMO

BACKGROUND & AIMS: This study aims to assess the nutritional status of patients during the different phases of the Chimeric Antigen Receptor (CAR)-T cell therapy and to identify prominent risk factors of hypoalbuminemia in patients after CAR-T treatment. The clinical consequences of malnutrition in cancer patients have been highlighted by growing evidence from previous clinical studies. Given CAR-T cell therapy's treatment intensity and possible side effects, it is important to provide patients with sufficient medical attention and support for their nutritional well-being. METHODS: This study was conducted from May 2021 to December 2021 among patients undergoing CAR-T cell therapy at the Bone Marrow Transplantation Center in The First Affiliated Hospital of Zhejiang University School of Medicine. Logistic regression analysis was performed to investigate the risk factors associated with hypoalbuminemia. Participants were divided into the cytokine release syndrome (CRS) group (n = 60) and the non-CRS group (n = 11) to further analyze the relationship between hypoalbuminemia and CRS. RESULTS: CRS (OR = 13.618; 95% CI = 1.499-123.709; P = 0.013) and baseline albumin (ALB) (OR = 0.854; 95% CI = 0.754-0.967; P = 0.020) were identified as the independent clinical factors associated with post-CAR-T hypoalbuminemia. According to the nadir of serum albumin, hypoalbuminemia occurred most frequently in patients with severe CRS (78.57%). The nadir of serum albumin (r = - 0.587, P < 0.001) and serum albumin at discharge (r = - 0.315, P = 0.01) were negatively correlated for the duration of CRS. Furthermore, patients with hypoalbuminemia deserved longer hospitalization (P = 0.04). CONCLUSIONS: CRS was identified as a significant risk factor associated with post-CAR-T hypoalbuminemia. An obvious decline in serum albumin was observed as the grade and duration of CRS increase. However, further research is still needed to elucidate the mechanisms of CRS-associated hypoalbuminemia.


Assuntos
Neoplasias Hematológicas , Hipoalbuminemia , Receptores de Antígenos Quiméricos , Humanos , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Hipoalbuminemia/complicações , Imunoterapia Adotiva/efeitos adversos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/tratamento farmacológico , Fatores de Risco , Albumina Sérica , Terapia Baseada em Transplante de Células e Tecidos
4.
Support Care Cancer ; 30(4): 3321-3327, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34988704

RESUMO

PURPOSE: The influence of innovative chimeric antigen receptor T cell (CAR-T) therapy for hematological malignancies on nutritional status remains unknown. Therefore, we aim to explore the alterations of nutritional status after CAR-T cell therapy in patients with hematological malignancies. METHODS: We retrospectively collected the data of patients with acute leukemia (AL), lymphoma, and multiple myeloma (MM), who underwent CAR-T therapy at our hospital from 2018 to 2020. The serum albumin, triglyceride, and cholesterol before and 7, 14, and 21 days after CAR-T cell infusion were compared and analyzed. RESULT: A total of 117 patients were enrolled, consisting of 39 AL, 23 lymphoma, and 55 MM patients. The baseline albumin, triglyceride, and cholesterol were 37.43 ± 5.08 mg/L, 1.63 ± 0.74 mmol/L, and 3.62 ± 1.03 mmol/L, respectively. The lowest albumin level was found at 7 days after CAR-T cell infusion compared with baseline (P < 0.001), while the levels of triglyceride increased at 14 and 21 days (P < 0.001, P = 0.036). The levels of cholesterol at 7, 14, and 21 days after CAR-T cell infusion were lower than baseline (all P < 0.05). Spearman's correlation coefficient showed cytokine release syndrome grade was negatively correlated with the levels of albumin at 7 days and cholesterol at 21 days after CAR-T cell infusion (r = - 0.353, P < 0.001; r = - 0.395, P = 0.002). CONCLUSION: The alterations of different nutrition-related biochemical parameters varied after CAR-T cell therapy. The levels of albumin and total cholesterol after CAR-T cell infusion were negatively correlated with the grade of cytokine release syndrome. Specific screening and intervention for malnutrition in patients receiving CAR-T cell therapy need to be explored in further studies.


Assuntos
Neoplasias Hematológicas , Imunoterapia Adotiva , Estado Nutricional , Terapia Baseada em Transplante de Células e Tecidos , Neoplasias Hematológicas/terapia , Humanos , Receptores de Antígenos Quiméricos , Estudos Retrospectivos
5.
Acta Haematol ; 144(5): 500-507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33690228

RESUMO

Patients receiving a hematopoietic cell transplant are thought to be at increased risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus infectious disease 2019. Transplant activities at our center continue, and notably, no patient has been infected with SARS-CoV-2. Indeed, social distancing, masking, and education for patients and donors are major pillars of prevention. We recommend potential transplant recipients and donors to be tested for SARS-CoV-2 with qRT-PCR, serum antibody detection, and a lung CT scan pretransplant. If possible, stem cells from HLA-matched unrelated donors by local processing laboratories should be cryopreserved and shipped before initiating pretransplant conditioning. An alternative HLA-haplotype-matched related donor should be identified and evaluated as a backup. The interval immediately after discharge is the time of greatest risk for SARS-CoV-2 infection because of travel and exposure to infected persons. We recommend self-isolation and minimal contact with family members. Nonessential clinic visits should be deferred or substituted with telemedicine consultations if possible. These recommendations are based on our experience at a major transplant center in China. Although some recommendations are evidence based, other recommendations are not and warrant validation in controlled trials.


Assuntos
COVID-19/epidemiologia , Transplante de Células-Tronco Hematopoéticas , COVID-19/patologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Humanos , Pulmão/diagnóstico por imagem , Pandemias , SARS-CoV-2/isolamento & purificação , Doadores de Tecidos/psicologia
6.
BMC Cancer ; 19(1): 242, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885156

RESUMO

BACKGROUND: Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG). CASE PRESENTATION: Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient's general condition remains good. CONCLUSIONS: This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Decitabina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Cladribina/uso terapêutico , Citarabina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Indução de Remissão/métodos , Terapia de Salvação/métodos , Irmãos , Transplante Haploidêntico/métodos , Resultado do Tratamento
7.
BMC Cancer ; 19(1): 486, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31122200

RESUMO

Following publication of the original article [1], the authors reported that the incorrect Fig. 2A was published in the article. The recovery times required to achieve a normal neutrophil count was omitted. The corrected Fig. 2 is given below.

8.
Mycopathologia ; 181(9-10): 753-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27350325

RESUMO

Cunninghamella bertholletiae as a rare cause of mucormycosis has been described almost exclusively in immunosuppressed patients such as hematopoietic stem cell transplant (HSCT) recipients. The infection is associated with high rates of mortality despite aggressive treatment. We describe a 40-year-old male with HLA-haploidentical HSCT developed fungal pneumonitis caused by C. bertholletiae complicated by graft failure and prolonged neutropenia. The patient died 102 days after HSCT despite early use of posaconazole and amphotericin B, which are believed to be the two most effective antifungal antibiotics against C. bertholletiae. The case highlights extreme unfavorable outcome in C. bertholletiae infection and neutropenia as a major risk factor.


Assuntos
Cunninghamella/classificação , Cunninghamella/isolamento & purificação , Rejeição de Enxerto/complicações , Transplante de Células-Tronco Hematopoéticas , Mucormicose/diagnóstico , Mucormicose/patologia , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Evolução Fatal , Humanos , Masculino , Técnicas Microbiológicas , Microscopia , Mucormicose/microbiologia , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Transplantados , Triazóis/uso terapêutico
9.
Front Oncol ; 11: 755584, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868965

RESUMO

Multiple myeloma (MM) with central nervous system (CNS) involvement is rare with only 1% incidence. So far, there is no standard or effective treatment for CNS MM, and the expected survival time is fewer than 6 months. Here, we report a case of MM with CNS involvement presented with cauda equina syndrome (CES) who achieved complete remission after anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy (Chictr.org.cn, ChiCTR1800017404). The expansion of BCMA CAR-T cells was observed in both peripheral blood (PB) and cerebrospinal fluid (CSF). The CAR-T cells peaked at 2.4 × 106/l in CSF at day 8 and 4.1 × 109/l in PB at day 13. The peak concentration of interleukin (IL)-6 in CSF was detected 3 days earlier, and almost five times higher than that in PB. Next, morphological analysis confirmed the elimination of nucleated cells in CSF 1 month after CAR-T cell treatment from 300 cells/µl, and the patient achieved functional recovery with regressed lesion shown in PET-CT. The case demonstrated that BCMA CAR-T cells are effective and safe in this patient population.

10.
Bone Marrow Transplant ; 55(4): 717-721, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32005917

RESUMO

Treatment of acute lymphoblastic leukemia (ALL) is still a challenge despite years of researching, especially for those of poor prognosis. Zhang and his team recently proved that FLT3 gene mutation was identified in ~5% of ALL and the mutation spectrum is different from AML. Recently, chimeric antigen receptor T cells (CART) therapy presents great efficacy in treating refractory leukemia. We report a case of a refractory ALL patient with FLT3-ITD mutations and unfavorable karyotypes, who failed to respond to chemotherapy and small molecule tyrosine kinase inhibitors, successfully treated by CART therapy. FLT3-ITD mutations were downregulated dramatically into 14.1% positive 3 days after the infusion and remained negative until now. MRD has stayed to be negative from the 10th day. This case suggests that CART-cell therapy might be effective in treating FLT3-ITD positive refractory ALL, implying the possibility to overcome the traditional prognosis scoring system for leukemia and providing a new chance for other leukemia patients with inferior prognosis factors.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Linfócitos B , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Receptores de Antígenos Quiméricos/genética , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico , Tirosina Quinase 3 Semelhante a fms/genética
11.
Curr Res Transl Med ; 68(3): 111-118, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32620465

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Atenção à Saúde/organização & administração , Neoplasias Hematológicas/terapia , Imunoterapia Adotiva , Controle de Infecções/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Receptores de Antígenos de Linfócitos T/imunologia , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Atenção à Saúde/métodos , Atenção à Saúde/normas , Atenção à Saúde/tendências , Neoplasias Hematológicas/epidemiologia , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Controle de Infecções/métodos , Controle de Infecções/normas , Controle de Infecções/tendências , Pneumonia Viral/epidemiologia , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/organização & administração , Serviços Preventivos de Saúde/normas , Serviços Preventivos de Saúde/tendências , SARS-CoV-2
12.
Bone Marrow Transplant ; 54(7): 969-972, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30563981

RESUMO

Adoptive transfer of T cells modified to express chimeric antigen receptors (CARs) targeting CD19 (CART19s) has demonstrated impressive results in treating B-cell malignancies. Although CART19-induced complications have been gradually recognized, local cytokine-release syndrome (CRS) at particular parts of the body has not been extensively studied. In this paper, we firstly present a successfully treated case of severe dyspnea caused by the rapid enlargement of cervical lymph node following CART19 therapy in a relapsed/refractory DLBCL patient, with emphasis on the recognition, workup, and treatment. This report reminds for a careful evaluation and observation of the pre-existing mass, which could enlarge rapidly again as a result of CRS and be life threatening, in the CART therapy.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Dispneia/etiologia , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/complicações , Receptores de Antígenos Quiméricos/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade
13.
J Vasc Access ; 18(5): 396-401, 2017 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-28777395

RESUMO

INTRODUCTION: This pilot exploratory study aimed to compare the health-related quality of life (HRQOL) among patients diagnosed with different types of cancer receiving peripherally inserted central catheters (PICCs). METHODS: A multicenter cross-section study of cancer patients with PICCs was performed from February 1, 2013 to April 24, 2014. The primary objective of this study was to compare HRQOL in different cancer type patients with PICC. HRQOL was examined based on European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30). Multiple linear regression models were conducted for coping with potential confounding variables. We also examined PICC-related quality of daily life with a self-made questionnaire. RESULTS: Three hundred and fifty-seven cancer patients with PICC completed the survey in nine teaching hospitals. Lung cancer patients with PICC reported the worst dyspnea. Digestive tract cancer patients reported the worst appetite loss. Patients with hematologic malignancy reported the worst emotional, social function, fatigue and financial impact. Breast cancer patients reported better HRQOL. Baseline variables were proven not significant predictors of EORTC QLQ-C30 global health status. In self-made survey, pain after PICC insertion was null or a little in 98.6% of cancer patients. Limitation of upper extremity activity was null or a little in 94.1% of patients. CONCLUSIONS: HRQOL varies in different types of cancer patients with PICC. PICC may have a low impact on cancer patients' HRQOL. Further large sample studies are needed.


Assuntos
Antineoplásicos/administração & dosagem , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Neoplasias/tratamento farmacológico , Qualidade de Vida , Administração Intravenosa , Adulto , Idoso , China , Estudos Transversais , Feminino , Hospitais de Ensino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/psicologia , Projetos Piloto , Inquéritos e Questionários
14.
J Vasc Access ; 18(2): 153-157, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28218366

RESUMO

PURPOSE: To evaluate incidence and risk factors of peripherally inserted central catheter (PICC)-related complications in cancer patients. METHODS: A prospective, multicenter, cohort study of cancer patients with PICC insertion was performed from February 1, 2013 to April 24, 2014. All patients were monitored in clinic until PICCs were removed. The primary endpoint was PICC removal due to complications. Patient-, catheter- and insertion-related factors were analyzed in univariable and multivariable logistic regression analysis to identify significant independent risk factors for PICC-related complications. RESULTS: There were 477 cancer patients included, for a total of 50,841 catheter-days. Eighty-one patients (17.0%) developed PICC-related complications, with an incidence of 1.59 per 1000 catheter days. Thirty-six (7.5%) PICCs were removed because of complications. The most common complications were skin allergy (4.6%), catheter occlusion (3.4%) and accidental withdrawal (2.3%). Nine (1.9%) patients developed symptomatic upper extremity deep venous thrombosis (UEDVT) and central line associated bloodstream infection (CLABSI) was shown in six (1.3%) PICCs with an infection rate 0.12 per 1000 catheter days. In multivariable analysis, body mass index (BMI) >25 (odds ratio, 2.09; 95% confidence interval, 1.26-3.47, p = 0.004) was shown to be a significant risk factor for PICC complications. CONCLUSIONS: Cancer patients with BMI greater than 25 were more likely to have PICC complications.


Assuntos
Antineoplásicos/administração & dosagem , Obstrução do Cateter , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Dermatite Alérgica de Contato/epidemiologia , Neoplasias/tratamento farmacológico , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , China/epidemiologia , Dermatite Alérgica de Contato/diagnóstico , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/diagnóstico , Razão de Chances , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa Profunda de Membros Superiores/diagnóstico , Adulto Jovem
15.
Clin Cancer Res ; 23(13): 3297-3306, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28039267

RESUMO

Purpose: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor-modified T cells against CD19 (CART19) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited.Experimental Design: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine- and cyclophosphamide-based lymphodepletion. The postinfusion responses, toxicities, expansion, and persistence of CART19s in enrolled patients were observed and monitored.Results: We enrolled 15 patients with R/R ALL. The median transduction efficiency of CART19s was 33%. In vitro cytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 × 106/kg to 9.8 × 106/kg. Twelve patients achieved complete remission 1 month after CART19s infusion. CART19s expanded and persisted in peripheral blood and bone marrow. At 150 days, the overall survival rate and leukemia-free survival rate were 65.5% and 37.8%, respectively. The cumulative incidence of relapse and the nonrelapse mortality rate were 54.5% and 7.7%, respectively. Four patients underwent subsequent haploidentical hematopoietic stem cell transplantation. In this trial, 10 patients experienced cytokine release syndrome (CRS). Grade 3 CRS developed in 40% of patients and was associated with a higher disease burden on day -1 and a higher number of previous relapses.Conclusions: This trial demonstrated potent antileukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation. Clin Cancer Res; 23(13); 3297-306. ©2016 AACR.


Assuntos
Antígenos CD19/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Adulto , China , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptores de Antígenos de Linfócitos T/administração & dosagem , Recidiva , Indução de Remissão , Linfócitos T/efeitos dos fármacos
16.
J Hematol Oncol ; 9(1): 70, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27526682

RESUMO

UNLABELLED: Chimeric antigen receptor-modified (CAR) T cells targeting CD19 (CART19) have shown therapeutical activities in CD19+ malignancies. However, the etiological nature of neurologic complications remains a conundrum. In our study, the evidence of blood-brain barrier (BBB)-penetrating CAR T cells as a culprit was revealed. A patient with acute lymphocytic leukemia developed sustained pyrexia with tremors about 6 h after CART19 infusion, followed by a grade 2 cytokine release syndrome (CRS) and neurological symptoms in the next 3 days. Contrast-enhanced magnetic resonance showed signs of intracranial edema. Lumbar puncture on day 5 showed an over 400-mmH2O cerebrospinal pressure. The cerebrospinal fluid (CSF) contained 20 WBCs/µL with predominant CD3+ T cells. qPCR analysis for CAR constructs showed 3,032,265 copies/µg DNA in CSF and 988,747 copies/µg DNA in blood. Cytokine levels including IFN-γ and IL-6 in CSF were extremely higher than those in the serum. Methyprednisone was administrated and the symptoms relieved gradually. The predominance of CART19 in CSF and the huge discrepancies in cytokine distributions indicated the development of a cerebral CRS, presumably featured as CSF cytokines largely in situ produced by BBB-penetrating CAR T cells. For the first time, we reported the development of cerebral CRS triggered by BBB-penetrating CAR T cells. TRIAL REGISTRATION: ChiCTR-OCC-15007008 .


Assuntos
Antígenos CD19/imunologia , Imunoterapia Adotiva/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Antígenos CD19/líquido cefalorraquidiano , Barreira Hematoencefálica/metabolismo , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Citocinas/líquido cefalorraquidiano , Citocinas/metabolismo , Feminino , Humanos , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Prednisona/uso terapêutico , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 11(5): 508-11, 2003 Oct.
Artigo em Zh | MEDLINE | ID: mdl-14575547

RESUMO

To explore the hematopoietic reconstitution and transplantation-related complications of two units of unrelated umbilical cord blood combined transplantation for the treatment of adult hematologic malignancies, one adult patient with chronic myelogenous leukemia received two units of unrelated umbilical cord blood combined transplantation. The conditioning regimen was busulfan and cyclophosphamide (Bu-Cy). GVHD prophylaxis regimen consisted of mycophenolate mofetil (MMF), cyclosporine A (CsA) and methotrexate (MTX). The patient received total nucleated cells 4.63 x 10(7)/kg with CD34+ cells 8.34 x 10(5)/kg. Engraftment was documented by the analysis of short tandem repeat with polymerase chain reaction (STR-PCR). The results showed that the STR-PCR analysis for peripheral blood at day 31, 46 and 71 after transplantation suggested that one of two units of cord blood were completely engrafted. The ANC > 0.5 x 10(9)/L in the patient occurred at day 23, blood platelet counts > 20 x 10(9)/L at day 33 and > 50 x 10(9)/L at day 47. The Philadelphia chromosome and bcr/abl fusion gene of the patient also turned to negative after engraftment. Acute GVHD grade II occurred at day 13 and cured after treatment. It is concluded that umbilical cord blood can be used in adult hematopoietic stem cell transplantation. Two or more units umbilical cord blood combined transplantation might be the way to solve the problem of the low counts of nucleated cells when be used for adult.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/terapia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Contagem de Leucócitos
18.
Zhonghua Er Ke Za Zhi ; 42(11): 835-9, 2004 Nov.
Artigo em Zh | MEDLINE | ID: mdl-15631711

RESUMO

OBJECTIVE: Allogeneic bone marrow transplantation has been established as a standard method for the treatment of a range of malignant and non-malignant hematologic diseases in children. Unfortunately, fewer than 30% of patients have a human leukocyte antigen (HLA)-matched sibling. Advances in our understanding of the HLA system and the development of large international donor registries encourage the increasing use of unrelated donors as an alternative source of stem cells. The purpose of this study was to evaluate the clinical efficacy and safety of unrelated donor allogeneic bone marrow transplantation (URD-BMT) for the treatment of childhood leukemia. METHODS: Six patients with leukemia received URD-BMT. Two of them suffered from chronic myeloid leukemia (CML), 3 suffered from acute lymphocytic leukemia (ALL) and 1 suffered from acute promyelocytic leukemia (APL) (CR2). All cases were facilitated by Tzu Chi Marrow Donor Registry (TCTMDR). The high resolution DNA test for classIand II was carried out in HLA typing of all donor-receiver pairs. HLA allele matched in three cases, mismatched with one locus in two cases and with two loci in one case. All patients were prepared with cyclophosphamide (CY) 60 mg/kg/day for 2 days (total dose 120 mg/kg) and busulfan (Bu) 1 mg/kg x 4/day for 4 days (total dose 16 mg/kg). Mycophenolate mofetil (MMF), CsA and MTX were given to prevent acute graft-versus-host-disease (aGVHD). CsA of 3 mg/kg/d was continuously given by i.v. infusion, and then 6mg/kg/d by oral. The blood CsA concentration was 200 - 300 ng/ml. MTX was given at the dosage of 15 mg/m(2) on d 1 and 10 mg/m(2) on d 3, 6,9 or 11. MMF was given at the dosage of 0.25 - 0.5 g/d from day 0 to day 120. Prostaglandin E1 was given to prevent the hepatic veno-occlusive disease (VOD), Ganciclovir was used to prevent CMV infection until the CMV antigenemia became negative. RESULTS: Analysis of DNA short tandem repeats showed total engraftment of donor marrow after transplantation in all cases. The median time when granulocyte exceeded 0.5 x 10(9)/L was 14.5 (13 - 18) days, platelets exceeded 20 x 10(9)/L was 16 (14 - 23) days. The acute GVHD grade II-IV occurred in 2 of 6 (33.3%) patients. There were 3 cases with chronic GVHD and none of them developed with the extensive chronic GVHD. All patients were alive in disease-free situation now with median follow-up 412 (187 - 1338) days. CONCLUSION: URD-BMT is an effective method for the treatment of childhood leukemia.


Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Criança , Humanos , Imunossupressores/uso terapêutico , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
19.
Zhonghua Xue Ye Xue Za Zhi ; 25(2): 74-7, 2004 Feb.
Artigo em Zh | MEDLINE | ID: mdl-14990043

RESUMO

OBJECTIVE: To compare the clinical outcomes between HLA allele matched (HLA-M) and 1 approximately 2 alleles disparity mismatched (HLA-mis) unrelated allogeneic bone marrow transplantation (URD-BMT). METHODS: Thirty-nine patients received HLA-M and 21 received HLA-mis URD-BMT for the treatment of acute leukemia, chronic myeloid leukemia in chronic phase (CP) and myelodysplastic syndromes (MDS) in our hospital between November 1998 and December 2002. Conditioning regimen was Bu 16 mg/kg plus CTX 120 mg/kg, and mycophenolate mofetil (MMF), CsA and MTX were given to prevent aGVHD. RESULTS: Thirty-eight of the HLA-M group and 18 of the HLA-mis group were engrafted successfully. The median follow-up duration was 11 (2.5 - 52.0) months for HLA-M group and 9 (2 - 46) months for HLA-mis group. The 3-year probabilities of disease-free survival (DFS) for HLA-M and HLA-mis group were (79.2 +/- 7.1)% and (45.8 +/- 15.5)%, respectively (P < 0.05). Grade II - IV aGVHD occurred in 10 (26.3%) patients in HLA-M group and 6 (33.3%) in HLA-mis group, respectively (P > 0.05). CONCLUSION: URD-BMT is an effective modality for the treatment of leukemia and MDS. The outcome after URD-BMT can be optimized by matching the HLA-A, B and DR alleles between the donor and recipient.


Assuntos
Alelos , Transplante de Medula Óssea , Teste de Histocompatibilidade , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Feminino , Humanos , Leucemia/mortalidade , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Transplante Homólogo
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