RESUMO
Although skin complications are common adverse events from tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML), no reports have focused on skin and soft tissue infections (SSTIs) associated with TKI use. We herein present five episodes of SSTIs in three CML patients under dasatinib treatment. All patients were adolescents and had been receiving dasatinib for more than 4 years. In contrast, none of 41 adult CML patients experienced SSTIs in a retrospective analysis. Our findings suggest that long-term dasatinib treatment in adolescent patients may be associated with the increased risk of SSTIs.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Infecções dos Tecidos Moles , Adolescente , Adulto , Dasatinibe/efeitos adversos , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Infecções dos Tecidos Moles/induzido quimicamenteRESUMO
BACKGROUND: Acute kidney injury (AKI) is a complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Increasing severity of AKI is associated with an increased risk of death. However, the impact of AKI in patients with malignant versus nonmalignant disease has not been reported. We investigated the incidence of AKI within the first 100 days after allo-HSCT and the impact of AKI on both 3-year overall survival (OS) and cumulative incidence of death after allo-HSCT in all patients and in patients with/without malignant primary diseases. METHODS: We performed a retrospective analysis of 107 consecutive pediatric and young adult patients who received their first allo-HSCT. AKI was classified into three grades according to the Acute Kidney Injury Network classification system. RESULTS: The cumulative incidences of AKI stages 1-3, 2-3, and 3, at day 100 after allo-HSCT were 34.6% (95% confidence interval [CI], 25.7%-43.6%), 17.8% (95% CI, 11.2%-25.6%), and 3.7% (95% CI, 1.2%-8.6%), respectively. OS was reduced for patients with AKI compared with patients without AKI (60.4% vs. 79.6%, p = .038). The cumulative incidence of death in the AKI group with nonmalignant disease was significantly higher than that in the no-AKI group (44.4% vs. 0%, p = .003). CONCLUSION: AKI after allo-HSCT was not only a frequent event but also related to reduced OS. We recommend that all patients receiving allo-HSCT, especially patients with nonmalignant diseases, be closely monitored for AKI.
Assuntos
Injúria Renal Aguda , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adolescente , Criança , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our knowledge, no report has evaluated the glomerular filtration rate (GFR) in pediatric patients who underwent HSCT using the gold standard GFR measurement, as well as inulin-based GFR (iGFR). METHODS: We assessed iGFR before and after allo-HSCT to evaluate the impact of allo-HSCT on GFR in a prospective cohort study of 17 pediatric patients. We also assessed the accuracy and bias of the values of estimated GFR (eGFR) calculated using serum creatinine (Cr), cystatin C (CysC), beta-2 microglobulin (ß2 MG), 24-h creatinine clearance (24hCcr), and the full chronic kidney disease in children (CKiD) index that combines Cr, CysC, and blood urea nitrogen-based equations with iGFR as a reference to identify the most reliable equation for GFR. RESULTS: There was no significant difference between the values before and after allo-HSCT. CKiD CysC-, 24hCcr-, and full CKiD-based values showed good within 30% (P30) accuracy (80.6%, 79.3%, and 80.6%, respectively), but only 24hCcr and full CKiD had good mean bias (8.5% and 8.9%, respectively) and narrow 95% limits of agreement (-32.2 to 52.7 mL/min/1.73 m2 and -29.3 to 47.4 mL/min/1.73 m2 , respectively) compared with the corresponding iGFR. CONCLUSION: There was no significant impact of allo-HSCT on GFR in our cohort. The most reliable equations for pediatric patients with allo-HSCT were eGFR-24hCcr and eGFR-full CKiD.
Assuntos
Biomarcadores/análise , Taxa de Filtração Glomerular , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Inulina/análise , Rim/fisiopatologia , Adolescente , Criança , Pré-Escolar , Creatinina/sangue , Cistatina C/sangue , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Humanos , Testes de Função Renal , Masculino , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: The spectrum of late sequelae after hematopoietic stem cell transplantation (HSCT) includes infertility, which is the most frequent complication. Some reports suggested that ovarian function may be better preserved in females undergoing HSCT with reduced-intensity conditioning (RIC) than with conventional myeloablative conditioning (MAC). However, the impact of HSCT after 8-Gy TBI-based reduced-toxicity MAC (RTMAC), whose efficacy is between those of conventional MAC and RIC, on ovarian function remains unclear. PROCEDURE: A single-center retrospective analysis of data derived from patient information for all the children who underwent transplantation at the Shinshu University Hospital was carried out. Patients who underwent 8-Gy total body irradiation (TBI)-based RTMAC before HSCT were analyzed. RESULTS: A total of 36% (five of 14) of the patients developed primary ovarian insufficiency (POI) during the observation period, but serum follicle-stimulating hormone levels reduced to normal range with spontaneous menstruation in two, implying the reversal of POI. Furthermore, only one (10%) of the 10 prepubertal patients (71%; 10/14) at the time of HSCT suffered from POI at the last observation, but all three post-pubertal patients developed POI (100%), and two (67%) continued to suffer from POI at the last observation. CONCLUSIONS: Taken together, 8-Gy TBI-based RTMAC before HSCT may decrease the possibility of POI compared with conventional MAC, especially in prepubertal patients. A longer follow-up will be required to ascertain whether a normal pregnancy and delivery can occur in such patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infertilidade Feminina/etiologia , Leucemia/terapia , Agonistas Mieloablativos/uso terapêutico , Ovário/efeitos da radiação , Insuficiência Ovariana Primária/prevenção & controle , Condicionamento Pré-Transplante , Adolescente , Criança , Pré-Escolar , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Lactente , Leucemia/complicações , Projetos de Pesquisa , Estudos Retrospectivos , Irradiação Corporal Total/efeitos adversos , Adulto JovemAssuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica , Piebaldismo , Doenças da Imunodeficiência Primária , Humanos , Transplante de Medula Óssea/efeitos adversos , Ciclofosfamida/uso terapêutico , Doenças da Imunodeficiência Primária/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Condicionamento Pré-Transplante/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
BACKGROUND: Encouraging responses to histone deacetylase inhibitors have been reported for hematologic malignancies. Here, we report effects of panobinostat and 5-azacytidine on the proliferation of juvenile myelomonocytic leukemia (JMML) CD34+ cells. PROCEDURE: We previously reported that stimulation of JMML CD34+ cells with stem cell factor and thrombopoietin on irradiated murine AGM-S3 cells led to substantial expansion of JMML CD34+ cells that contained leukemic stem cells capable of transplantation into immunodeficient mice. Using this culture system, we evaluated effects of panobinostat and 5-azacytidine on the proliferation of JMML CD34+ cells. RESULTS: Panobinostat dose dependently reduced the numbers of day 7 CD34+ cells generated under stimulation of hematopoietic growth factors on AGM-S3 cells in all eight patients with JMML. These patients possessed various genetic and/or karyotypic abnormalities. CD34+ CD38- cells were substantially more sensitive to panobinostat at 10 and 20 nM than CD34+ CD38+ cells. Panobinostat, however, failed to influence the ability of AGM-S3 cells to stimulate JMML CD34+ cell production. In contrast to HL60 cells, apoptosis and cell cycle arrest in panobinostat-mediated inhibition were at low levels in JMML. The inhibitor also suppressed the factor-dependent proliferation of normal CD34+ cells on AGM-S3 cells. Meanwhile, no substantial inhibitory effects of 5-azacytidine on the growth of JMML CD34+ cells were observed. CONCLUSIONS: These results demonstrate that panobinostat directly suppresses the growth of JMML CD34+ cells, in particular CD34+ CD38- cells, regardless of the genetic abnormality type, suggesting that it is a useful antileukemic drug to target JMML stem cells at a pretransplant stage.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Leucemia Mielomonocítica Juvenil , Panobinostat/farmacologia , Animais , Antígenos CD34 , Azacitidina/farmacologia , Linhagem Celular , Pré-Escolar , Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Camundongos , Células Tumorais CultivadasRESUMO
AdV11-HC is one of the major complications after allogeneic HSCT in Japan. We previously reported that the intravenous infusion of ganciclovir was effective against AdV11-HC in a post-transplant patient. We here report a case of a 10-year-old boy who underwent cord blood transplantation for the treatment of relapsed lymphoblastic lymphoma. He developed AdV11-HC with an elevated AdV load in his urine and blood on day 14 after HSCT. He was immediately treated with intravenous ganciclovir; he rapidly achieved a remission of AdV11-HC with a decreased AdV load in his urine and blood. He remained in remission of AdV11-HC, even after we switched ganciclovir to oral valganciclovir on day 63. A pharmacokinetics study of his urine revealed that therapeutic concentrations of ganciclovir could be achieved by both intravenous ganciclovir and oral valganciclovir. These findings suggested that both intravenous ganciclovir and oral valganciclovir could be promising alternatives for the treatment of AdV11-HC in post-transplant patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Inulina , Criança , Creatinina , Taxa de Filtração Glomerular , Humanos , RimRESUMO
Mucolipidosis (ML) II alpha/beta is an autosomal recessive disease caused by reduced enzyme activity of N-acetylglucosamine-1-phosphotransferase. Clinical symptoms of ML II are severe psychomotor delay and dysostosis multiplex; death usually occurs by 5-8 years of age from cardiopulmonary complications. Allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted for ML; however, few reports have documented the detailed outcomes of HSCT for ML. A 26-month-old girl received a human leukocyte antigen 3/6-allele-matched transplant from cord blood. The preparative regimen consisted of fludarabine, cyclophosphamide, 6-Gy total body irradiation, and rabbit antithymocyte globulin. Although comparing before and after cord blood transplantation results, we observed that lysosomal enzyme activities in the plasma decreased by approximately 20-40%. Low serum levels of immunoglobulin A, G2, and G4 were also observed before HSCT; however, these values normalized after transplantation. Despite undergoing HSCT, she was treated twice for bacterial pneumonia with acute respiratory distress syndrome at ages 37 and 38 months. Although HSCT effects on the clinical manifestations were limited, laboratory data including plasma lysosomal enzyme activities and serum levels of immunoglobulin showed improvement.
Assuntos
Anormalidades Múltiplas/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Mucolipidoses/genética , Transtornos Psicomotores/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Anormalidades Múltiplas/sangue , Anormalidades Múltiplas/fisiopatologia , Anormalidades Múltiplas/terapia , Animais , Pré-Escolar , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunoglobulinas/sangue , Mucolipidoses/sangue , Mucolipidoses/fisiopatologia , Mucolipidoses/terapia , Transtornos Psicomotores/sangue , Transtornos Psicomotores/fisiopatologia , Transtornos Psicomotores/terapia , Coelhos , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
Mechanisms of relapse of acute lymphoblastic leukemia (ALL) after human leukocyte antigen (HLA) class II mismatched hematopoietic stem cell transplantation (HSCT) remain unclear. We report two children with relapsed ALL after HSCT from related donors with HLA-DRB1 and -DQB1 mismatches in the graft versus host direction. One lost HLA-DRB1, DQB1, and DPB1 alleles, and the other lost one HLA haplotype of the leukemic blasts at relapse. HLA class II loss may be a triggering event for ALL relapse after partially HLA-mismatched-related HSCT. In addition, HLA typing of relapsed leukemic blasts could be vital in the selection of retransplant donors.
Assuntos
Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Histocompatibilidade Classe II/genética , Recidiva Local de Neoplasia/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Alelos , Criança , Feminino , Doença Enxerto-Hospedeiro/imunologia , Cadeias beta de HLA-DP/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Histocompatibilidade , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologiaRESUMO
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects of nicotinamide adenine dinucleotide phosphate oxidase. Catalase-positive bacteria and fungi are phagocytosed, but persist within phagocytes, resulting in granulomatous inflammation. Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CGD, HSCT sometimes leads to fatal outcomes related to the exacerbation of persistent infectious or post-infectious inflammatory diseases, particularly in adolescent and young adult patients with a history of recurrent infections and/or multiple granulomas in organs. Here, we present the case of a young adult with X-linked CGD in whom multiple lesions were found in lungs and lymph nodes on both computed tomography and positron emission tomography (PET) scans before allogeneic HSCT, but all the lesions disappeared only on PET scan 5 months after HSCT. Monitoring the activity of multiple pre-existing lesions with PET scan may be beneficial to adolescent and young adult CGD-patients undergoing allogeneic HSCT.
Assuntos
Doença Granulomatosa Crônica/diagnóstico por imagem , Doença Granulomatosa Crônica/terapia , Transplante de Células-Tronco Hematopoéticas , Aloenxertos , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adulto JovemRESUMO
A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT.
Assuntos
Vacinas Anticâncer/efeitos adversos , Células Dendríticas/transplante , Transplante de Células-Tronco Hematopoéticas/métodos , Fragmentos de Peptídeos/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/imunologia , Proteínas WT1/administração & dosagem , Adolescente , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Criança , Células Dendríticas/imunologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Segurança , Doadores de Tecidos , Vacinação/efeitos adversos , Proteínas WT1/imunologia , Proteínas WT1/uso terapêuticoRESUMO
BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency that affects phagocytic cells. CGD patients are susceptible to fungal infections, especially Aspergillus infections. The management of life-threatening Aspergillus infections in CGD is particularly difficult because some infections cannot be eradicated with standard antifungal treatments and, hence, result in death. CASE REPORT: A 2-week-old girl developed invasive pulmonary aspergillosis, which rapidly progressed to respiratory failure. Liposomal amphotericin B, micafungin, and voriconazole were not effective. At the age of 2 months, she was diagnosed with p67phox-deficient CGD. In addition to antifungal treatment, the patient received 21 granulocyte transfusions (GTX), which were obtained from 300- or 400-mL whole blood samples from healthy random donors who were not treated with granulocyte-colony-stimulating factor or dexamethasone. The median neutrophil count of the GTX was 1.88 × 10(8) /kg body weight. Rituximab was administered to reduce alloimmunization to human leukocyte antigens (HLA) after the eighth GTX, resulting in their absence of anti-HLA before and after cord blood transplantation (CBT). A marked improvement in her invasive pulmonary aspergillosis was achieved, although the first CBT was rejected. Complete hematopoietic recovery was obtained after the second CBT. CONCLUSION: Repeated GTX containing relatively low doses of neutrophils might be able to control severe Aspergillus infections in infants with CGD.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/terapia , Doença Granulomatosa Crônica/tratamento farmacológico , Doença Granulomatosa Crônica/terapia , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/terapia , Neutrófilos/citologia , Terapia Combinada , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Humanos , Recém-NascidoRESUMO
No standard treatment has been established in childhood blastic plasmacytoid dendritic cell neoplasma (BPDCN) because of its rarity. We treated with acute lymphoblastic leukemia-type regimen for a child with BPDCN with skin and leukemic involvement. She has been disease-free for 4 years after allogeneic bone marrow transplantation in first complete remission. In 33 cases of pediatric BPDCN, the over survival was significantly lower in the patients with skin manifestation than those without cutaneous involvement. Accordingly, it is important to determine whether allogeneic hematopoietic stem cell transplantation should be applied to first complete remission in the patients with poor prognosis.
Assuntos
Células Dendríticas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Neoplasias Cutâneas/terapia , Pré-Escolar , Feminino , Neoplasias Hematológicas/patologia , Humanos , Neoplasias Cutâneas/patologia , Transplante HomólogoRESUMO
Tacrolimus is widely used as prophylaxis for graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (allo-HSCT). It has a narrow therapeutic index range; high tacrolimus concentrations are associated with toxicity, whereas low concentrations are associated with an increased risk of GVHD. Although dose adjustments based on therapeutic drug monitoring are performed, unexpected large variations in tacrolimus concentration are sometimes encountered. The available evidence suggests that the factors affecting tacrolimus concentration are not fully understood. This study was aimed primarily at investigating the factors affecting day-to-day variations in tacrolimus concentration in children and young adults who received continuous tacrolimus infusion after allo-HSCT. The secondary objective was to identify the factors causing large variations (>20%) in tacrolimus concentrations. This retrospective cohort study comprised 123 consecutive pediatric and young adult patients (age <25 years) who received continuous i.v. tacrolimus infusion after allo-HSCT at Shinshu University Hospital, Matsumoto, Japan, between January 2009 and December 2021. To compare day-to-day variations in tacrolimus concentration without consideration of the tacrolimus dose, 2 consecutive days when the tacrolimus dose was not changed were selected from between the first post-allo-HSCT day of a tacrolimus concentration >7 ng/mL and day 28 post-allo-HSCT. Subsequently, information for the subsequent 24 hours was collected along with the tacrolimus concentrations and hematocrit values. Tacrolimus concentration was determined using whole blood samples. Tacrolimus concentrations were significantly higher in patients who received red blood cell concentrate (RCC) transfusions (P < .0001) and methotrexate (P = .0162), patients with persistent fever (P = .0056), and patients with a decline in fever (P = .0003). In contrast, tacrolimus concentrations were significantly lower in patients who received platelet concentrate (PC) transfusions (P < .0001), who redeveloped fever (P = .0261), and who had a replaced tacrolimus administration route set (P = .0008). Variations in tacrolimus concentration were significantly correlated with variations in hematocrit (r = .556; P < .0001). Body weight (P < .0001), RCC transfusion (P < .0001), methotrexate use (P = .0333), persistent fever (P = .0150), and decline in fever (P = .0073) were associated with a sharp increase in tacrolimus concentration. In contrast, body weight (P < .0001), PC transfusion (P = .0025), and replacement of the tacrolimus administration route set (P = .0025) were associated with a sharp decrease in tacrolimus concentration. RCC and PC transfusions, fever, methotrexate administration, and replacement of the tacrolimus administration route set were independent factors affecting day-to-day variations in tacrolimus concentration. In addition to these factors, low body weight was a risk factor for both sharp increases and decreases in tacrolimus concentration. These findings suggest the need for better control of tacrolimus concentration using whole blood samples.
Assuntos
Carcinoma de Células Renais , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias Renais , Humanos , Adulto Jovem , Criança , Adulto , Tacrolimo/uso terapêutico , Metotrexato/uso terapêutico , Estudos Retrospectivos , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológicoRESUMO
Epidermal growth factor receptor (EGFR) is overexpressed in various cancers, including non-small cell lung cancer (NSCLC), and in some somatic cells at a limited level, rendering it an attractive antitumor target. In this study, we engineered chimeric antigen receptor (CAR)-T cells using the piggyBac transposon system, autologous artificial antigen-presenting cells, and natural ligands of EGFR. We showed that this approach yielded CAR-T cells with favorable phenotypes and CAR positivity. They exhibited potent antitumor activity against NSCLC both in vitro and in vivo. When administered to tumor-bearing mice and non-tumor-bearing cynomolgus macaques, they did not elicit toxicity despite their cross-reactivity to both murine and simian EGFRs. In total we tested three ligands and found that the CAR candidate with the highest affinity consistently displayed greater potency without adverse events. Taken together, our results demonstrate the feasibility and safety of targeting EGFR-expressing NSCLCs using ligand-based, piggyBac-engineered CAR-T cells. Our data also show that lowering the affinity of CAR molecules is not always beneficial.
RESUMO
[This corrects the article DOI: 10.1016/j.omto.2023.100728.].
RESUMO
We report a pediatric case of critical illness polyneuropathy and myopathy caused by Bacillus cereus sepsis during acute lymphoblastic leukemia therapy. A 15-year-old boy developed B. cereus sepsis and multiple organ failure on the 19th day after initiation of chemotherapy, and multidisciplinary treatment was started. Treatment was effective and septic shock with multiple organ failure remitted. He was weaned from a respirator on day 23 after the onset of sepsis, but complete flaccid paralysis of the 4 extremities occurred. His compound muscle action potential and F-wave occurrence were reduced on a nerve conduction test. The number of motor units was markedly decreased, and the amplitude and duration of individual motor units were low and short, respectively, on electromyography. Cerebrospinal fluid was normal. On the basis of these findings, he was diagnosed with critical illness polyneuropathy/myopathy. He underwent intensive rehabilitation and recovered the ability to walk 3 months after onset. He was discharged 1 year after the initiation of chemotherapy, and remission has been maintained without inconvenience to daily living activities for 3 years since disease onset.
Assuntos
Bacillus cereus/patogenicidade , Doenças Musculares/etiologia , Polineuropatias/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Sepse/complicações , Adolescente , Eletromiografia , Humanos , Masculino , Insuficiência de Múltiplos Órgãos , Doenças Musculares/diagnóstico , Polineuropatias/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
Metastatic non-small cell lung cancer (NSCLC) remains largely incurable and the prognosis is extremely poor once it spreads to the brain. In particular, in patients with brain metastases, the blood brain barrier (BBB) remains a significant obstacle for the biodistribution of antitumor drugs and immune cells. Here we report that chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR) exhibit antitumor activity in vitro against tumor cell lines and lung cancer organoids, and in vivo in xenotransplant models of orthotopic and metastatic NSCLC. The co-expression of the CCL2 receptor CCR2b in B7-H3.CAR-T cells, significantly improves their capability of passing the BBB, providing enhanced antitumor activity against brain tumor lesions. These findings indicate that leveraging T-cell chemotaxis through CCR2b co-expression represents a strategy to improve the efficacy of adoptive T-cell therapies in patients with solid tumors presenting with brain metastases.
Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos T , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A 7-year-6-month-old female was diagnosed with a pelvic malignant peripheral nerve sheath tumor and lymph node metastases. Tumorectomy was performed after four cycles of chemotherapy. A 33-mm cystic lesion was observed around the left iliac muscle after three cycles of postoperative chemotherapy, and proton beam therapy (PBT) was recommended. She was referred for absorbable spacer (AS) placement. The left ovarian appendage (OA) was resected due to the direct tumor infiltration. The right OA was fixed to the uterosacral ligament. The AS was fixed to the lateral pelvis. The PBT (70.3 Gy relative biological effectiveness) was performed successfully with the AS, and she also had the reproducing possibility due to prevention of severe irradiation damage of the right OA. AS eliminated the surgical removal of spacers and enabled us high-dose PBT for residual tumor without severe irradiation damage including infertility.