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This study aimed to evaluate the efficacy and safety of chidamide (Chi) combined with a modified Busulfan-Cyclophosphamide (mBuCy) conditioning regimen for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only in the same period. The leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse-related mortality (NRM) were evaluated. Patients in the Chi group were associated with lower 2-year CIR (19.0 vs. 41.4%, P = 0.030), better 2-year LFS (76.1 vs. 48.1%, P = 0.014), and had no significant difference in 2-year OS (80.5 vs. 66.4%, P = 0.088). Patients with minimal residual disease (MRD) positive before HSCT in the Chi group exhibited an advantage in 2-year LFS and a trend towards better 2-year OS (75.0 vs. 10.2%, P = 0.048; 75.0 vs. 11.4%, P = 0.060, respectively). Multivariable analysis showed that the chidamide intensified regimen was independently associated with better LFS (HR 0.23; 95%CI, 0.08-0.63; P = 0.004), and showed no significant impact with OS for all patients (HR 0.34, 95%CI, 0.11-1.07; P = 0.064). The cumulative incidence rates of grade II-IV aGVHD were similar (36.4 vs. 38.6%, P = 0.858). 20 patients in Chi group evinced an elevation in γ-glutamyltransferase, as compared to the mBuCy group (90.9 vs. 65.9%, P = 0.029). No transplantation-related mortality was documented within the first 100 days after transplantation. The results demonstrate that the chidamide intensified regimen may be an effective and acceptable safety option for T-ALL/LBL undergoing allo-HSCT, and further validation is needed.
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Condicionamento Pré-Transplante , Humanos , Masculino , Feminino , Condicionamento Pré-Transplante/métodos , Adulto , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Adolescente , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Taxa de Sobrevida , Transplante Homólogo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/mortalidade , Intervalo Livre de Doença , Estudos Retrospectivos , AloenxertosRESUMO
BACKGROUND: Our study aims to comprehensively assess nutrition status and malnutritional prevalence in early allogenic hematopoietic stem cell transplant (allo-HSCT) patients. METHODS: This single-center, cross-sectional study included 171 patients within the 90 days post-transplantation (from September 2019 to April 2020). Data collected included demographic, 3 day 24-h diet record, a Patient-Generated Subjective Global Assessment (PG-SGA) tool, laboratory tests, anthropometric indices, and body composition. RESULTS: One hundred and seventy-one patients with a mean age of 37.8 ± 11.3 and a male to female ratio of 102 to 69 were included. According to PG-SGA, 115 (67.3%) indicated the critical need for nutritional intervention and symptom management (PG-SGA score > 9). Forty-three (43.3%) of patients had experienced insufficient intakes of energy according to a 24-h diet record. Our study found that 120 (70.2%) patients had a body fat percentage and high triacylglycerol (64.9%). Reduced free fat mass index and low hand-grip strength were found in 133 (77.78%) and 104 (60.81%), respectively. The prevalence of malnutrition was 24.6% and the prevalence of sarcopenia was 13.5%. CONCLUSION: Although the prevalence was not high, this research has demonstrated a high risk of malnutrition and a lower muscle mass in early allo-HSCT. Furthermore, our study confirmed body composition assessment would be an excellent way to identify malnutrition precisely.
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Transplante de Células-Tronco Hematopoéticas , Desnutrição , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Avaliação Nutricional , Estudos Transversais , Estado Nutricional , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Few prospective studies have examined posttransplant chimeric antigen receptor (CAR) T cell infusion as candidates for front-line consolidation therapy for high-risk multiple myeloma (MM) patients. This single-arm exploratory clinical trial is the first to evaluate the safety and efficacy of sequential anti-CD19 and anti-BCMA CAR-T cell infusion, followed by lenalidomide maintenance after autologous stem cell transplantation (ASCT), in 10 high-risk newly diagnosed multiple myeloma (NDMM) patients. The treatment was generally well tolerated, with hematologic toxicities being the most common grade 3 or higher adverse events. All patients had cytokine release syndrome (CRS), which was grade 1 in 5 patients (50%) and grade 2 in 5 patients (50%). No neurotoxicity was observed after CAR-T cell infusion. The overall response rate was 100%, with the best response being 90% for a stringent complete response (sCR), and 10% for a complete response (CR). At a median follow-up of 42 (36-49) months, seven (70%) of 10 patients showed sustained minimal residual disease (MRD) negativity for more than 2 years. The median progression-free survival (PFS) and overall survival (OS) were not reached. Although the sample size was small and there was a lack of control in this single-arm study, the clinical benefits observed warrant ongoing randomized controlled trials.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Imunoterapia Adotiva/efeitos adversos , Lenalidomida , Mieloma Múltiplo/tratamento farmacológico , Estudos Prospectivos , Transplante AutólogoRESUMO
The present study aimed to investigate the efficacy and safety for alternate application of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) combined with idarubicin (IDA)/daunorubicin (DNR) in treatment of acute promyelocytic leukemia (APL). A total of 72 ALP patients were divided into the low/medium risk and high risk groups according to the WBC and PLT levels. All APL patients received induction therapy, consolidation therapy and maintenance therapy in treatment under careful nursing monitoring. The complete response (CR) rate was 87.5% (63/72), with 95.12% (39/41) in the low/medium risk group, which was markedly higher than the 77.42% (24/31) high risk group. The PML/RAR α fusion negative rate was also markedly higher in the low/medium risk group (95.12%, 39/41) than the high risk group (77.42%, 24/31). The duration for PML/RAR α fusion negative was also significantly shorter in the low/medium risk group. Recurrence was found in cases in the low/medium risk group, markedly lower than cases in the high risk group. The overall survival (OS) time was markedly longer in low/medium risk patients high. Alternate application of the combination strategy could achieve well CR rate with less complications. And patients with low/medium risk had better clinical outcomes and prognosis than high risk patients.
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Trióxido de Arsênio/uso terapêutico , Daunorrubicina/uso terapêutico , Idarubicina/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Trióxido de Arsênio/administração & dosagem , Estudos de Coortes , Daunorrubicina/administração & dosagem , Humanos , Idarubicina/administração & dosagem , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/patologia , Estudos Prospectivos , Tretinoína/administração & dosagemRESUMO
PURPOSE: To explore the best schedule of oral cryotherapy for the prevention of oral mucositis in recipients of myeloablative hematopoietic stem cell transplantation (HSCT). METHODS: A prospective randomized study was conducted to recruit allogeneic HSCT recipients, who were then randomly allocated into four arms to accept the following: oral cryotherapy during the whole course (arm A) or second half of the course (arm B) of cytotoxic agents administration, regular oral cryotherapy twice a day (arm C), or conventional oral care without cryotherapy (arm D). Status of oral mucositis was daily assessed from the first day of conditioning to the 15th day post-HSCT. A myeloablative conditioning regimen was used which was composed of busulfan, cyclophosphamide, and cytarabine. RESULTS: Totally 160 cases were consecutively enrolled in this study, and 145 cases were eligible for oral mucositis assessment. Both arm A and arm B were associated with a lower incidence and short duration of severe mucositis (≥ grade 3), although no statistical difference was found between these two groups (p = 0.463, p = 0.678). The highest incidence of severe mucositis was observed in arm C. Recovery of mucositis also had a significant diversity among the 4 arms (F = 4.133, p = 0.008). CONCLUSIONS: Risk and outcome of severe oral mucositis could be ameliorated by oral cryotherapy during the administration of cytotoxic agents for allogeneic HSCT patients receiving non-radiation myeloablative conditioning regimen, and a half-course schedule could acquire a comparable efficacy compared with the whole-course schedule.
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Crioterapia/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Agonistas Mieloablativos/efeitos adversos , Estomatite/prevenção & controle , Estomatite/terapia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Estudos Prospectivos , Estomatite/induzido quimicamente , Adulto JovemRESUMO
Interferon-α (IFN-α) inhibits tumor growth and mimics graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current case-control study, we compared treatment responses in acute leukemia patients with relapse tendency post-allo-HSCT receiving preemptive IFN-α after withdrawal of immunosuppressants (n = 31) vs. receiving no IFN-α (n = 67). In the IFN-α group, 25 patients responded to the treatment without progressing to hematological relapse. In the non-IFN-α group, only 22 patients responded to the treatment. The response rate differed significantly (80.6 vs. 32.8%, P < 0.001). The 2-year cumulative incidence of relapse was 31.6 and 61.2% in the IFN-α and the non-IFN groups, respectively (P = 0.006). The 2-year leukemia-free survival and overall survival rate was 57.4 vs. 28.4% (P < 0.001) and 67.6 vs. 32.9% (P = 0.001), respectively. Among the 31 patients in the IFN-α group, 18 patients (58.1%) developed graft-versus-host disease (GVHD): 6 acute and 12 limited chronic GVHD. Patients who developed GVHD had higher treatment response rate than patients without GVHD (88.9 vs. 53.8%, P = 0.022). In conclusion, preemptive IFN-α therapy is a safe and effective treatment to prevent disease progression in high-risk patients with relapse tendency post-allo-HSCT.
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Transplante de Células-Tronco Hematopoéticas , Interferon-alfa/administração & dosagem , Leucemia , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de SobrevidaRESUMO
Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation-based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post-allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed.
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Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto JovemRESUMO
AIM: This study aimed to explore the association between patient-reported items at different time points after hematopoietic stem cell transplantation (HSCT) and long-term survival. METHODS: We conducted a study with 144 allogeneic HSCT patients, following them for 5 years post-transplantation. Data from the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire were collected before transplantation and at 1, 3, 6, 12, 18, 36, and 60 months after transplantation. Demographic characteristics and survival status were also assessed. RESULTS: Among the 144 cases, the 5-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease-free (GRFS) rates were 65%, 48%, 17%, and 36% respectively. Health-related quality of life (HRQOL) showed a fluctuating pattern over 5 years. Using a latent class mixed model, patients were classified into two groups based on their physical well-being (PWB) scores during the 60-month follow-up. Class 1 had initially lower PWB scores, which gradually increased over time. In contrast, Class 2 maintained higher PWB scores with slight increases over time. Kaplan-Meier survival analysis revealed that Class 1 had better OS (70.9% vs. 52.9%, p = 0.021), PFS (60.5% vs. 41.2%, p = 0.039), and GRFS (35.1% vs. 29.3%, p = 0.035) compared to Class 2. CONCLUSIONS: Patients who had higher initial PWB scores after HSCT demonstrated improved long-term survival outcomes. The PWB score could serve as a valuable predictor for the prognosis of HSCT.
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Transplante de Células-Tronco Hematopoéticas , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Doença Enxerto-Hospedeiro/etiologia , Adolescente , Inquéritos e QuestionáriosRESUMO
Effectively addressing the challenges posed by relapsed and refractory diffuse large B-cell lymphoma, particularly when employing autologous hematopoietic stem cell transplantation and CAR-T therapy, requires a comprehensive approach to treatment and nursing. This case report emphasizes a nursing strategy focused on managing neurotoxicity post-CAR-T therapy. Nursing interventions include the identification of neurotoxicity symptoms, neuropsychiatric management, careful support during lumbar puncture and intrathecal administration, psychological assistance, and adaptive nutritional guidance. The diligent application of treatment and nursing care resulted in a remarkable recovery for the patient, as evidenced by the alleviation of central facial paralysis, improvement in swallowing function (from Grade 4 to Grade 2), and enhanced vocalization. Consistent and specialized nursing care is paramount for effectively managing complications, especially neurotoxicity, in patients undergoing CAR-T therapy. A thorough monitoring of symptoms and personalized care contribute to optimizing treatment outcomes and ensuring patient safety.
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Environmental temperature affects the composition, structure, and function of the gut microbial communities in host animals. To elucidate the role of gut microbiota in thermal adaptation, we designed a 2 species × 3 temperatures experiment, whereby we acclimated adult males of two agamid lizard species (warm-climate Leiolepis reevesii and cold-climate Phrynocephalus przewalskii) to 20, 28, and 36°C for 2 weeks and then collected their fecal and small-intestinal samples to analyze and compare the microbiota using 16S rRNA gene amplicon sequencing technology. The fecal microbiota displayed more pronounced interspecific differences in microbial community than the small-intestinal microbiota in the two species occurring in thermally different regions. The response of fecal and small-intestinal microbiota to temperature increase or decrease differed between the two species, with more bacterial taxa affected by acclimation temperature in L. reevesii than in P. przewalskii. Both species, the warm-climate species in particular, could cope with temperature change by adjusting the relative abundance of functional categories associated with metabolism and environmental information processing. Functional genes associated with carbohydrate metabolism were enhanced in P. przewalskii, suggesting the contribution of the fecal microbiota to cold-climate adaptation in P. przewalskii. Taken together, our results validate the two hypotheses tested, of which one suggests that the gut microbiota should help lizards adapt to thermal environments in which they live, and the other suggests that microbial communities should be thermally more sensitive in warm-climate lizards than in cold-climate lizards.
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OBJECTIVE: We aimed to evaluate the efficacy of decitabine consolidation after treatment with CD19/CD22 chimeric antigen receptor T-cell (CAR-T) for patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL). METHODS: We retrospectively analysed 48 patients with r/r B-ALL who received CD19/CD22 CAR-T therapy between September 2017 and May 2021. Sixteen patients received decitabine consolidation (20â¯mg/m2/day for 5 days at 3-month intervals) after CAR-T therapy (DAC group), while 32 patients did not receive decitabine consolidation (CON group). Overall survival (OS), leukaemia-free survival (LFS), and cumulative incidence of relapse (CIR) were evaluated in both groups. Time-to-event analysis was performed using the Kaplan-Meier method. RESULTS: The median follow-up periods in the DAC and CON groups were 41.2 months and 28.6 months, respectively. The 4-year OS and 4-year LFS rates in both groups were 93.3â¯% and 64.3â¯% (P=0.029) and 87.5â¯% and 55.9â¯% (P=0.059), respectively. The 1-year CIR was 6.25â¯% and 28.6â¯%, respectively. Univariate and multivariate Cox regression analyses showed that decitabine consolidation after CAR-T therapy was significantly associated with superior OS (hazard ratio [HR]: 0.121, 95â¯% confidence interval [CI]: 0.015-0.947, P=0.044), and bridging to haematopoietic stem cell transplantation after CAR-T therapy was significantly associated with superior LFS (HR: 0.279, 95â¯%CI: 0.093-0.840, P=0.023). CONCLUSIONS: Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.
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PURPOSE: Despite chimeric antigen receptor (CAR) T-cell therapy has achieved great advances in recent year, approximately 50% of relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL) patients treated with CAR-T experience relapse 6 months post CAR-T treatment. CD20 express on 30 to 50% of B-ALL, which makes CD20 Monoclonal Antibody as one of the potential therapy strategies to decrease the tumor burden and improve the efficacy of CAR-T therapy. Adding Rituximab to chemotherapy protocol had been demonstrated to improve the outcome for CD20-positive ALL. However, rare study explored the influence of Rituximab combined with CAR-T therapy. METHODS: We retrospectively analyzed 20 r/r B-ALL patients who received CAR-T therapy, all of whom had failed multiple lines of therapy. Before CAR-T infusion, we administered Rituximab to 10 patients with high CD20 expression at a dose of 375 mg/m2 for 1 day. Meanwhile, we selected 10 patients with the comparable features who underwent CAR-T treatment without Rituximab in the same period as the control group. In vitro, the surface molecule expression and killing of CAR-T post Rituximab-treated B-ALL cells co-incubated with CAR-T cells were detected by flow cytometry. RESULTS: The median follow-up of Rituximab and Control groups were 29.27 and 9.83 months. We found that adding Rituximab may confer a favorable prognosis compared with Control group. The 2-year overall survival (OS) and leukemia-free survival (LFS) rates both were longer in the Rituximab group (90% vs. 26.7%, p = 0.0342; 41.7% vs. 25%, p = 0.308). In vitro, we observed that Rituximab-treated tumour cells are more sensitive to CAR-T killing and a broad range of cytokines and chemokines were produced when Rituximab-treated Nalm-6 cells co-cultured with 19-22CAR-T cells, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). To investigate whether Rituximab has an effect on CAR-T persistence, we stimulated CAR-T cells repeatedly in vitro with Rituximab-treated Nalm-6 to evaluate the changes in CAR-T surface exhaustion molecules at different times. We found that the expression of exhaustion molecules (LAG-3, PD-1, TIM-3) on CAR-T cells were significantly lower in the Rituximab group than in the Control group. CONCLUSION: Rituximab combined with CAR-T therapy is effective for improving the long-term prognosis of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improves CAR-T efficacy by sensitizing ALL to CART-mediated cytotoxicity and reducing CAR-T exhaustion.
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The purpose of this paper is to study the feasibility and economic benefits of intelligent medical Internet of Things (IOT) systems for improving the quality of life of hemophilia patients, thereby reducing the risk of teratogenicity and disability for patients. This article selects 60 severe hemophilia patients who were followed up in our hospital from 2018 to 2019 as the research object. In the intelligent medical system, the Gaussian mixture model discretization algorithm is used to preprocess patient data collection. The observation group uses the intelligent medical system to implement home nursing for the patients, and the control group uses ordinary home nursing. This paper evaluates the quality of life of the two groups of patients 6 months after the intervention, including self-care ability, transfer function, and home nursing cognitive ability. The research results show that the home nursing based on smart medical IOT proposed in this paper is feasible and effective for improving the quality of life of patients. It can effectively improve the patient's self-care ability and joint functions and has important reference value for the development of intelligent medical IOT equipment.
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Hemofilia A , Internet das Coisas , Hemofilia A/terapia , Assistência Domiciliar , Humanos , Inteligência , Internet , Qualidade de VidaRESUMO
OBJECTIVE: To assess changes of nutritional status by comprehensive nutrition assessment including nutritional risk screening, dietary assessment, blood biochemical index, and body composition in acute leukemia patients who had undergone chemotherapy. METHODS: A total of 169 patients with acute leukemia treated at The First Affiliated Hospital of Soochow University from June 2018 to August 2019 were recruited for this study. Before and after chemotherapy, the NRS-2002 and PG-SGA scales, dietary intake, blood biochemical index and body composition were evaluated to compare the changes of nutritional status. RESULTS: NRS-2002 score and PG-SGA score after chemotherapy were significantly increased than those before chemotherapy (P<0.001). Many patients had insufficient nutritional intake during chemotherapy, and the dietary intake score of patients with induction chemotherapy was significantly lower than that of patients with consolidation chemotherapy (P=0.043). The results of multivariate analysis showed that induction chemotherapy was the independent risk factor for the increase of PG-SGA scores and the decrease of dietary intake (all P<0.05). After chemotherapy, the white blood cell count, hemoglobin, and platelet count were significantly decreased (P<0.001), the prealbumin was significantly increased (P<0.001), and the blood glucose was increased (P=0.04), but albumin was not significantly changed. The weight, body mass index, fat-free mass, skeletal muscle mass and intracellular water were all significantly decreased (P<0.001), and visceral fat area was increased significantly after chemotherapy (P<0.05), especially in newly-diagnosed acute lymphoblastic leukemia patients after the induction of chemotherapy. CONCLUSION: The nutritional status of patients with acute leukemia has undergone significant changes after chemotherapy. A single indicator has limited significance for nutritional status assessment. Comprehensive assessment of nutritional status by multiple tools is worthy of clinical application.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Humanos , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Avaliação Nutricional , Estado Nutricional , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
The 7 + 3 regimen is the front-line induction chemotherapy in patients with newly diagnosed acute myeloid leukemia, with a response rate of 60-80%. But it's not suitable for all patients especially old/unfit patients because of a higher treatment related toxicity. Therefore, safer and more effective induction therapies are required. In this retrospective study, 50 patients with newly diagnosed acute myeloid leukemia received decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) as induction chemotherapy. Complete remission (CR) rate was 96% (48/50) and overall response rate was 100%. Of note, All 7 patients harboring FLT3-ITD mutation achieved CR. The median overall survival (OS) was 40.0 months (range 2.0, 58.0). The OS at 1, 3, and 5 years were 75.3%, 54.2%, and 49.3%. The median relapse free survival (RFS) was 38.0 months (range 2.0, 58.0). The RFS at 1, 3, and 5 years were 67.3%, 48.9%, and 45.1%. The OS and RFS of patients who received hematopoietic stem cell transplantation (HSCT) were significantly higher than those who did not undergo HSCT (p=0.017; 0.016). The incidence of grade 3-4 neutropenia and thrombocytopenia was 84% and 88%. Meanwhile, the incidence of grade 3-4 infection and bleeding was only 16% and 6%. There was no early death. In conclusion, DAC+HAAG regimen is effective and well-tolerated as induction therapy in patients with newly diagnosed AML.
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Relapsed/refractory acute myeloid leukemia (AML) patients generally have a dismal prognosis and the treatment remains challenging. Due to the expression of CD7 on 30% AML and not on normal myeloid and erythroid cells, CD7 is an attractive target for immunotherapy of AML. CD7-targeted CAR T-cells had demonstrated encouraging efficacy in xenograft models of AML. We report here on the use of autologous CD7 CAR T-cells in the treatment of a relapsed/refractory AML patient with complex karyotype, TP53 deletion, FLT3-ITD mutation, and SKAP2-RUNX1 fusion gene. Before the CAR T-cell therapy, the patient achieved partial remission with IA regimen and attained complete remission after reinduction therapy (decitabine and venentoclax). Relapse occurred after consolidation (CLAG regimen). Then she failed CLIA regimen combined with venetoclax and exhibited resistance to FLT3 inhibitors. Bone marrow showed 20% blasts (CD7+ 95.6%). A total dose of 5 × 106/kg CD7 CAR T-cells was administered after the decitabine +FC regimen. Seventeen days after CAR T-cells infusion, she achieved morphologic leukemia-free state. The patient developed grade 3 cytokine release syndrome. No severe organ toxicity or immune effector cell-associated neurotoxicity syndrome was observed. In summary, the autologous CD7 CAR T-cell therapy could be considered a potential approach for AML with CD7 expression (NCT04762485).Trial registration Clinical Trials.gov, NCT04762485. Registered on February 21, 2021, prospectively registered.
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Patients with relapsed/refractory early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) respond poorly to traditional therapy and have dismal prognosis. CD7 is a promising therapeutic targets for chimeric antigen receptor modified T cell therapy (CART) due to its widely expression in almost all T-cell malignancies. Here we present the anti-CD7 CART therapy in a 11-year-old male with TP53 mutated relapsed/refractory ETP-ALL/LBL. The patient suffered second relapse after haploidentical hematopoietic stem cell transplantation, showing resistance to 4 lines salvage therapies including venetoclax. Nanobody derived CD7-CART cells were manufactured by co-transducing CAR-T cells with a CD7 protein expression blocker. 70.5% of blasts (CD7 expression: 92.6%) and extensive extramedullary disease (mediastinal mass, enlarged lymph nodes and spleen) were observed prior to CD7-CART-cell therapy. A total of 5 × 106/kg donor-derived CD7-CART-cells were infused. Hematological and extramedullary remission were both achieved, with persistence of CD7-CART-cells be detected until the last followup at 96th days after the infusion. Reversible adverse effects including grade 3 cytokine release syndrome and macrophage activation syndrome were observed. This case demonstrated that CD7-CART was a potent and safe salvage therapy in relapsed/refractory ETP-ALL/LBL patient with high tumor burden.Trial registration: ClinicalTrials. gov, NCT04785833 , Registered on March 8, 2021, prospectively registered.
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Background/Aims: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion. Methods: Univariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed. Results: The predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06). Conclusions: We have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Receptores de Antígenos Quiméricos/genéticaRESUMO
Patients with relapsed/refractory acute myeloid leukemia (R/R AML) often show resistance to chemotherapy and have dismal outcomes. Therefore, it is urgent to develop new treatment strategies to address this problem. With tremendous achievement of chimeric antigen receptor T cells (CAR-T) therapy against B-cell malignancies, many efforts have been devoted to developing CAR-T therapy for R/R AML but with limited success, in part owing to a lack of specific targets. C-type lectin-like molecule-1 (CLL-1) is highly expressed on AML blasts with no expression on normal hematopoietic stem cells, which makes it an ideal target of immunotherapy for AML. Here, we report 2 R/R AML patients who relapsed after allogeneic stem cell transplantation and failed multiline salvage therapies including anti-CD38 CAR-T therapy, but were successfully treated with PD-1 silenced anti-CLL-1 CAR-T therapy. Both patients achieved molecular complete remission with incomplete hematologic recovery at 28 days of evaluation after CLL-1 CAR-T cell infusion. Cytokine release syndrome in cases 1 and 2 were grade 1 and 2, respectively. At the last follow-up, cases 1 and 2 had maintained continuous remission for 8 and 3 months, respectively. Our results demonstrated that CLL-1 CAR-T cells might be an effective and safe salvage therapy for AML patients with posttransplant relapse.
RESUMO
We used mitochondrial cytochrome b and ND4 genes and 9 microsatellite loci to determine genetic diversity, population structure, evolutionary history, and migration patterns within the Reeves' butterfly lizard Leiolepis reevesii (Agamidae). Considering molecular-based phylogeographical lineages, we then performed niche equivalency and similarity tests between divergent lineages. Phylogenetic analyses based on mitochondrial DNA (mtDNA) data revealed 2 lineages (A and B) diverging ≈0.84 million years ago and, respectively, restricted to the northern and southern portions of the Wuzhishan and Yinggeling mountain ranges. Lineage B contains individuals from southern Hainan; Lineage A includes individuals from all other localities and can be further divided into 3 clusters according to microsatellite data. The null hypothesis that the 2 lineages shared identical niches was rejected in all niche equivalency tests, indicating niche shifts during genetic divergence. Similarity tests provided evidence of niche conservatism, suggesting that the 2 lineages share more characteristics of their niche spaces than randomly expected. The niche similarity and equivalency tests indicated a complex niche pattern in which both lineages share a main portion of their ecological spaces. The climatic niche of Lineage B represented a marginal and specialized fraction of the entire ecological space of the climatic niche of Lineage A, with warmer conditions. Isolation caused by orogenesis and subsequent niche divergence, together with local adaptation, may have led to genetic differentiation and further lineage sorting in L. reevesii.