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OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.
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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.
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Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Humanos , Femenino , Masculino , Adulto , Movilización de Célula Madre Hematopoyética/efectos adversos , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Prospectivos , Depresión/etiología , Depresión/inducido químicamente , Adolescente , Adulto Joven , Ansiedad/etiología , Donantes de Tejidos , Anciano , Fatiga/etiología , AloinjertosRESUMEN
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.
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Neoplasias Hematológicas , Receptores Quiméricos de Antígenos , Humanos , Tromboelastografía , Inmunoterapia Adoptiva/efectos adversos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Hemorragia/diagnóstico , Hemorragia/etiología , Hemorragia/terapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
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.
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Neoplasias Hematológicas , Hipoalbuminemia , Receptores Quiméricos de Antígenos , Humanos , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/etiología , Hipoalbuminemia/complicaciones , Inmunoterapia Adoptiva/efectos adversos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/tratamiento farmacológico , Factores de Riesgo , Albúmina Sérica , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
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.
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Neoplasias Hematológicas , Inmunoterapia Adoptiva , Estado Nutricional , Tratamiento Basado en Trasplante de Células y Tejidos , Neoplasias Hematológicas/terapia , Humanos , Receptores Quiméricos de Antígenos , Estudios RetrospectivosRESUMEN
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.
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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.
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COVID-19/epidemiología , Trasplante de Células Madre Hematopoyéticas , COVID-19/patología , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/epidemiología , Trasplante de Células Madre Hematopoyéticas/psicología , Humanos , Pulmón/diagnóstico por imagen , Pandemias , SARS-CoV-2/aislamiento & purificación , Donantes de Tejidos/psicologíaRESUMEN
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.
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Infecciones por Coronavirus/prevención & control , Atención a la Salud/organización & administración , Neoplasias Hematológicas/terapia , Inmunoterapia Adoptiva , Control de Infecciones/organización & administración , Pandemias/prevención & control , Neumonía Viral/prevención & control , Receptores de Antígenos de Linfocitos T/inmunología , Betacoronavirus/fisiología , COVID-19 , Infecciones por Coronavirus/epidemiología , Atención a la Salud/métodos , Atención a la Salud/normas , Atención a la Salud/tendencias , Neoplasias Hematológicas/epidemiología , Humanos , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/tendencias , Control de Infecciones/métodos , Control de Infecciones/normas , Control de Infecciones/tendencias , Neumonía Viral/epidemiología , Servicios Preventivos de Salud/métodos , Servicios Preventivos de Salud/organización & administración , Servicios Preventivos de Salud/normas , Servicios Preventivos de Salud/tendencias , SARS-CoV-2RESUMEN
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.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Linfocitos B , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Receptores Quiméricos de Antígenos/genética , Lectina 2 Similar a Ig de Unión al Ácido Siálico , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
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.
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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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Decitabina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Cladribina/uso terapéutico , Citarabina/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Humanos , Inducción de Remisión/métodos , Terapia Recuperativa/métodos , Hermanos , Trasplante Haploidéntico/métodos , Resultado del TratamientoRESUMEN
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.
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Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Disnea/etiología , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/complicaciones , Receptores Quiméricos de Antígenos/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana EdadRESUMEN
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.
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Antineoplásicos/administración & dosificación , Cateterismo Venoso Central/instrumentación , Cateterismo Periférico/instrumentación , Catéteres de Permanencia , Catéteres Venosos Centrales , Neoplasias/tratamiento farmacológico , Calidad de Vida , Administración Intravenosa , Adulto , Anciano , China , Estudios Transversales , Femenino , Hospitales de Enseñanza , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/psicología , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
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.
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Antineoplásicos/administración & dosificación , Obstrucción del Catéter , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Dermatitis Alérgica por Contacto/epidemiología , Neoplasias/tratamiento farmacológico , Trombosis Venosa Profunda de la Extremidad Superior/epidemiología , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/microbiología , Cateterismo Venoso Central/instrumentación , Cateterismo Periférico/instrumentación , China/epidemiología , Dermatitis Alérgica por Contacto/diagnóstico , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/diagnóstico , Oportunidad Relativa , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Trombosis Venosa Profunda de la Extremidad Superior/diagnóstico , Adulto JovenRESUMEN
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.
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Antígenos CD19/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , Adulto , China , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Receptores de Antígenos de Linfocitos T/administración & dosificación , Recurrencia , Inducción de Remisión , Linfocitos T/efectos de los fármacosRESUMEN
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 .
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Antígenos CD19/inmunología , Inmunoterapia Adoptiva/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Antígenos CD19/líquido cefalorraquídeo , Barrera Hematoencefálica/metabolismo , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Citocinas/líquido cefalorraquídeo , Citocinas/metabolismo , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Prednisona/uso terapéutico , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
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.
Asunto(s)
Cunninghamella/clasificación , Cunninghamella/aislamiento & purificación , Rechazo de Injerto/complicaciones , Trasplante de Células Madre Hematopoyéticas , Mucormicosis/diagnóstico , Mucormicosis/patología , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Resultado Fatal , Humanos , Masculino , Técnicas Microbiológicas , Microscopía , Mucormicosis/microbiología , Tórax/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Receptores de Trasplantes , Triazoles/uso terapéuticoRESUMEN
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.
Asunto(s)
Alelos , Trasplante de Médula Ósea , Prueba de Histocompatibilidad , Adolescente , Adulto , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia/mortalidad , Leucemia/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Trasplante HomólogoRESUMEN
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.
Asunto(s)
Trasplante de Médula Ósea , Leucemia/terapia , Niño , Humanos , Inmunosupresores/uso terapéutico , Donantes de Tejidos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
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.