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1.
Best Pract Res Clin Haematol ; 37(2): 101561, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39098801

RÉSUMÉ

HLA class II antigen presentation is modulated by the activity of the peptide editor HLA-DM and its antagonist HLA-DO, with their interplay controlling the peptide repertoires presented by normal and malignant cells. The role of these molecules in allogeneic hematopoietic cell transplantation (alloHCT) is poorly investigated. Balanced expression of HLA-DM and HLA-DO can influence the presentation of leukemia-associated antigens and peptides targeted by alloreactive T cells, therefore affecting both anti-leukemia immunity and the potential onset of Graft versus Host Disease. We leveraged on a large collection of bulk and single cell RNA sequencing data, available at different repositories, to comprehensively review the level and distribution of HLA-DM and HLA-DO in different cell types and tissues of the human body. The resulting expression atlas will help future investigations aiming to dissect the dual role of HLA class II peptide editing in alloHCT, and their potential impact on its clinical outcome.


Sujet(s)
Antigènes HLA-D , Leucémies , Humains , Leucémies/thérapie , Leucémies/immunologie , Leucémies/génétique , Antigènes HLA-D/génétique , Antigènes HLA-D/immunologie , Transplantation de cellules souches hématopoïétiques , Présentation d'antigène , Peptides/immunologie , Peptides/génétique , Allogreffes
2.
Support Care Cancer ; 32(8): 512, 2024 Jul 13.
Article de Anglais | MEDLINE | ID: mdl-39001992

RÉSUMÉ

INTRODUCTION: Skeletal muscle function is an important prognostically relevant indicator in patients with acute leukemia (AL), but skeletal dysfunction during chemotherapy is not well understood. This study aimed to investigate the factors that influence changes in skeletal muscle function from before the start of chemotherapy to before allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This was a retrospective cohort study that included 90 patients with AL who underwent chemotherapy before transplantation to perform allo-HSCT (men, 67.3%; median age, 53 years). The outcome measure was defined as changes in skeletal muscle function from before chemotherapy to before allo-HSCT, and was assessed by measuring the psoas muscle index (PMI) as skeletal muscle quantity and computed tomography values (CTV) as skeletal muscle quality using a computed tomography scanner. We examined the differences in PMI and CTV before chemotherapy and allo-HSCT, and the factors associated with changes in PMI. RESULT: The mean PMI for before chemotherapy and allo-HSCT were 4.6 ± 1.4 cm2/m2 and 4.0 ± 1.3 cm2/m2 and significant differences were observed (p < 0.001). However, the mean CTV before chemotherapy and allo-HSCT were 47.3 ± 4.5 HU and 47.4 ± 5.0 HU, respectively, and no significant differences were found (p = 0.798). In stepwise multiple regression analysis, age and sex were identified as factors related to changes in PMI (age, p = 0.019; sex, p = 0.001). CONCLUSION: We found that skeletal muscle quantity decreased during chemotherapy in patients with AL and was influenced by male sex and older age. TRIAL REGISTRATION NUMBER:   TRIAL REGISTRATION NUMBER: 34-096(11,243). Date of registration: September 11, 2023.


Sujet(s)
Transplantation de cellules souches hématopoïétiques , Muscles squelettiques , Humains , Mâle , Adulte d'âge moyen , Femelle , Études rétrospectives , Adulte , Transplantation de cellules souches hématopoïétiques/méthodes , Muscles squelettiques/physiopathologie , Sujet âgé , Tomodensitométrie/méthodes , Études de cohortes , Leucémie aigüe myéloïde/traitement médicamenteux , Leucémie aigüe myéloïde/thérapie , Muscle iliopsoas , Jeune adulte , Leucémies/thérapie , Leucémies/traitement médicamenteux , Transplantation homologue/méthodes , Maladie aigüe , Antinéoplasiques/effets indésirables , Antinéoplasiques/administration et posologie
3.
Zhonghua Yi Xue Za Zhi ; 104(27): 2477-2482, 2024 Jul 16.
Article de Chinois | MEDLINE | ID: mdl-38978372

RÉSUMÉ

Acute leukemia is the most common hematopoietic stem cell malignant tumor in children, which ranks in the top one of the incidence of tumor in children, it is a major disease that affects the growth and survival of children. With the continuous improvement of medical diagnosis and treatment and the extensive development of immunotherapy, the survival rate and quality of life of children with acute leukemia have been significantly improved. In recent years, three cooperative groups of childhood leukemia have been established in China, and a series of high-level research results have been published. In the future, efforts should be made to promote the process of standardization and homogenization in the diagnosis and treatment of children's acute leukemia, explore the monitoring targets of sensitive residual diseases, and find the best treatment for refractory/recurrent cases. Speeding up the clinical research of new drugs will be an urgent problem and development direction in the field of acute leukemia diagnosis and treatment in children.


Sujet(s)
Leucémies , Humains , Chine , Enfant , Leucémies/diagnostic , Leucémies/thérapie , Maladie aigüe , Leucémie-lymphome lymphoblastique à précurseurs B et T/diagnostic , Leucémie-lymphome lymphoblastique à précurseurs B et T/thérapie , Immunothérapie , Qualité de vie
4.
Zhonghua Yi Xue Za Zhi ; 104(27): 2521-2528, 2024 Jul 16.
Article de Chinois | MEDLINE | ID: mdl-38978376

RÉSUMÉ

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.


Sujet(s)
Transplantation de cellules souches de sang du cordon , Maladie du greffon contre l'hôte , Antigènes HLA , Leucémies , Humains , Femelle , Mâle , Transplantation de cellules souches de sang du cordon/effets indésirables , Pronostic , Études rétrospectives , Enfant d'âge préscolaire , Enfant , Leucémies/génétique , Leucémies/thérapie , Antigènes HLA/génétique , Maladie du greffon contre l'hôte/étiologie , Donneurs de tissus , Test d'histocompatibilité , Transplantation de cellules souches hématopoïétiques/effets indésirables
5.
J Palliat Med ; 27(7): 879-887, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38990245

RÉSUMÉ

Background: Prior studies reveal a lack of illness understanding and prognostic awareness among patients with hematological malignancies. We evaluated prognostic awareness and illness understanding among patients with acute leukemia and multiple myeloma (MM) and measured patient-hematologist discordance. Methods: We prospectively enrolled patients with acute leukemia and MM at Mount Sinai Hospital or Yale New Haven Hospital between August 2015 and February 2020. Patients were administered a survey assessing prognostic awareness, goals of care (GOC), and quality of life. Hematologists completed a similar survey for each patient. We assessed discordance across the cohort of patients and hematologists using the likelihood-ratio chi-square test and within patient-hematologist pairs using the kappa (κ) statistic. Results: We enrolled 185 patients (137 with leukemia and 48 with MM) and 29 hematologists. Among patients, 137 (74%) self-identified as White, 27 (15%) as Black, and 21 (11%) as Hispanic. Across the entire cohort, patients were significantly more optimistic about treatment goals compared with hematologists (p = 0.027). Within patient-hematologist pairs, hematologists were significantly more optimistic than patients with respect to line of treatment (κ = 0.03). For both leukemia and MM cohorts, patients were significantly more likely to respond "don't know" or deferring to a faith-based response with 88 (64%) and 34 (71%), respectively, compared with only 28 (20%) and 11 (23%) of hematologists, respectively. Conclusions: We observed significant discordance regarding prognosis and GOC among patients with hematological malignancies and their hematologists. These data support future interventions to improve prognostic understanding among this patient population to facilitate informed treatment choices.


Sujet(s)
Myélome multiple , Qualité de vie , Humains , Myélome multiple/psychologie , Femelle , Mâle , Qualité de vie/psychologie , Adulte d'âge moyen , Sujet âgé , Pronostic , Études prospectives , Leucémies/psychologie , Leucémies/thérapie , Planification des soins du patient , Adulte , Sujet âgé de 80 ans ou plus , Enquêtes et questionnaires , Hospitalisation
6.
J Res Health Sci ; 24(2): e00615, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-39072551

RÉSUMÉ

BACKGROUND: Leukemia is the most common childhood malignancy. Identifying prognostic factors of patient survival and relapse using more reliable statistical models instead of traditional variable selection methods such as stepwise regression is of great importance. The present study aimed to apply a penalized semi-parametric mixture cure model to identify the prognostic factors affecting short-term and long-term survival of childhood leukemia in the presence of competing risks. The outcome of interest in this study was time to relapse. Study Design: A retrospective cohort study. METHODS: A total of 178 patients (0‒15 years old) with leukemia participated in this study (September 1997 to September 2016, followed up to June 2021) at Golestan University of Medical Sciences, Iran. Demographic, clinical, and laboratory data were collected, and then a penalized semi-parametric mixture cure competing risk model with smoothly clipped absolute deviation (SCAD) and least absolute shrinkage and selection operator (LASSO) regularizations was used to analyze the data. RESULTS: Important prognostic factors of relapse patients selected by the SCAD regularization method were platelets (150000‒400000 vs.>400000; odds ratio=0.31) in the cure part and type of leukemia (ALL vs. AML, hazard ratio (HR)=0.08), mediastinal tumor (yes vs. no, HR=16.28), splenomegaly (yes vs. no; HR=2.94), in the latency part. In addition, significant prognostic factors of death identified by the SCAD regularization method included white blood cells (<4000 vs.>11000, HR=0.25) and rheumatoid arthritis signs (yes vs. no, HR=5.75) in the latency part. CONCLUSION: Several laboratory factors and clinical side effects were associated with relapse and death, which can be beneficial in treating the disease and predicting relapse and death time.


Sujet(s)
Récidive , Humains , Enfant , Mâle , Femelle , Études rétrospectives , Enfant d'âge préscolaire , Facteurs de risque , Adolescent , Nourrisson , Pronostic , Iran/épidémiologie , Leucémies/mortalité , Leucémies/thérapie , Nouveau-né , Modèles statistiques , Leucémie aigüe myéloïde/mortalité , Modèles des risques proportionnels , Récidive tumorale locale , Leucémie-lymphome lymphoblastique à précurseurs B et T/mortalité , Numération des plaquettes
7.
Integr Cancer Ther ; 23: 15347354241261356, 2024.
Article de Anglais | MEDLINE | ID: mdl-38872330

RÉSUMÉ

BACKGROUND: Among leukemia patients, sleep disruptions are prevalent and can profoundly affect their overall quality of life. Acupressure and foot reflexology, modalities rooted in traditional Chinese medicine, have garnered attention for their potential to address sleep disturbances and mitigate associated symptoms. METHODS: This research utilized a randomized controlled trial with a pretest-posttest design involving 102 leukemia patients admitted to Imam Khomeini Hospital in Urmia. Participants were randomly allocated to 3 groups: acupressure (n = 34), reflexology (n = 34), or control (n = 34). Prior to the intervention, patients completed a demographic survey and the Pittsburgh Sleep Quality Index (PSQI) for baseline assessments. Acupressure involved stimulation of the SP6 point twice daily for 10 minutes over 4 weeks, while reflexology entailed daily 10-minute sessions with sweet almond oil on the soles for the same duration. The control group received standard care without additional interventions. Following the 4-week intervention period, post-intervention evaluations were conducted using identical measurement tools. RESULTS: The findings underscored the efficacy of both acupressure and foot reflexology in significantly improving sleep quality within the intervention groups (P < .001). Initially, there were no notable differences in sleep quality among the 3 groups (P > .05). Subsequently, pairwise comparisons adjusted with Bonferroni corrections revealed significant disparities in sleep quality between the acupressure and reflexology groups compared to the control group (P < .001). However, post-intervention analysis indicated no statistically significant variance in enhancing sleep quality between the acupressure and foot reflexology groups (P < .05). CONCLUSION: This study demonstrates that acupressure and foot reflexology interventions can enhance sleep quality in individuals with leukemia. These findings support the effectiveness of these complementary modalities, offering targeted relief and relaxation. While these non-invasive therapies show promise in improving well-being, further research is needed to confirm and expand upon these results due to study limitations.


Sujet(s)
Acupression , Pied , Leucémies , Qualité de vie , Qualité du sommeil , Humains , Acupression/méthodes , Mâle , Femelle , Adulte d'âge moyen , Adulte , Pied/physiopathologie , Leucémies/complications , Leucémies/thérapie , Massage/méthodes , Troubles de la veille et du sommeil/thérapie , Médecine traditionnelle chinoise/méthodes , Résultat thérapeutique
8.
Leuk Res ; 142: 107517, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38761563

RÉSUMÉ

BACKGROUND AND AIMS: Umbilical cord blood transplantation (UCBT) has emerged as a promising treatment option for patients with acute leukemia needing hematopoietic stem cell transplantation. Both single (sUCBT) and double cord blood units (dUCBT) demonstrate potential benefits, but studies comparing their effectiveness have shown mixed results. This meta-analysis aimed to determine the comparative safety and efficacy of sUCBT versus dUCBT in acute leukemia patients. METHODS: Electronic databases were systematically examined to identify relevant studies comparing single vs double UCBT published until November 2023. Nine studies involving 3864 acute leukemia patients undergoing UCBT were included. Outcomes analyzed were acute graft-versus-host disease (GVHD), chronic GVHD, relapse, non-relapse mortality, leukemia-free survival and overall survival. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model. RESULTS: The risk of Grade II-IV acute GVHD (RR 1.55, 95% CI 1.19-2.03) and Grade III-IV acute GVHD (RR 1.25, 95% CI 1.07-1.46) were significantly higher with dUCBT. Relapse risk was lower with dUCBT (RR 0.57, 95% CI 0.38-0.88) while overall survival favored sUCBT (RR 1.25, 95% CI 1.06-1.46). No significant differences were observed for chronic GVHD, non-relapse mortality or leukemia-free survival. CONCLUSION: Both single and double UCBT have potential as effective treatments for acute leukemia. The choice of treatment should consider various factors, including the risk of GVHD, relapse, and mortality. More research, especially randomized trials, is needed to provide definitive guidance on the optimal use of single and double unit UCBT in patients with acute leukemia.


Sujet(s)
Transplantation de cellules souches de sang du cordon , Maladie du greffon contre l'hôte , Humains , Transplantation de cellules souches de sang du cordon/méthodes , Transplantation de cellules souches de sang du cordon/effets indésirables , Maladie du greffon contre l'hôte/étiologie , Maladie du greffon contre l'hôte/mortalité , Leucémies/thérapie , Leucémies/mortalité , Leucémie aigüe myéloïde/thérapie , Leucémie aigüe myéloïde/mortalité , Maladie aigüe
9.
Blood ; 143(26): 2710-2721, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38728431

RÉSUMÉ

ABSTRACT: Over the last decades, significant improvements in reducing the toxicities of allogeneic hematopoietic cell transplantation (allo-HCT) have widened its use as consolidation or salvage therapy for high-risk hematological malignancies. Nevertheless, relapse of the original malignant disease remains an open issue with unsatisfactory salvage options and limited rationales to select among them. In the last years, several studies have highlighted that relapse is often associated with specific genomic and nongenomic mechanisms of immune escape. In this review we summarize the current knowledge about these modalities of immune evasion, focusing on the mechanisms that leverage antigen presentation and pathologic rewiring of the bone marrow microenvironment. We present examples of how this biologic information can be translated into specific approaches to treat relapse, discuss the status of the clinical trials for patients who relapsed after a transplant, and show how dissecting the complex immunobiology of allo-HCT represents a crucial step toward developing new personalized approaches to improve clinical outcomes.


Sujet(s)
Transplantation de cellules souches hématopoïétiques , Leucémies , Médecine de précision , Échappement de la tumeur à la surveillance immunitaire , Humains , Médecine de précision/méthodes , Transplantation de cellules souches hématopoïétiques/méthodes , Leucémies/thérapie , Leucémies/immunologie , Microenvironnement tumoral/immunologie , Transplantation homologue
10.
Cytotherapy ; 26(8): 878-889, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38703155

RÉSUMÉ

BACKGROUND AIMS: Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this approach strongly depends on the ex vivo generation of high-quality donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practices (GMP). We previously described a procedure for generating large numbers of donor-derived anti-leukemia CTL through stimulation of CD8-enriched lymphocytes with dendritic cells (DCs) pulsed with apoptotic LB in the presence of interleukin (IL)-12, IL-7 and IL-15. Here we report that the use of IFN-DC and the addition of IFNα2b during the priming phase significantly improve the generation of an efficient anti-leukemia T cells response in vitro. METHODS: Using this approach, 20 high-risk pediatric patients given haploidentical HSCT for high-risk acute leukemia were enrolled and 51 batches of advanced therapy medical products (ATMP), anti-leukemia CTL, were produced. RESULTS: Quality controls demonstrated that all batches were sterile, free of mycoplasma and conformed to acceptable endotoxin levels. Genotype analysis confirmed the molecular identity of the ATMP based on the starting biological material used for their production. The majority of ATMP were CD3+/CD8+ cells, with a memory/terminal activated phenotype, including T-central memory populations. ATMP were viable after thawing, and most ATMP batches displayed efficient capacity to lyse patients' LB and to secrete interferon-γ and tumor necrosis factor-α. CONCLUSIONS: These results demonstrated that our protocol is highly reproducible and allows the generation of large numbers of immunologically safe and functional anti-leukemia CTL with a high level of standardization.


Sujet(s)
Transplantation de cellules souches hématopoïétiques , Immunothérapie adoptive , Leucémies , Lymphocytes T cytotoxiques , Humains , Lymphocytes T cytotoxiques/immunologie , Transplantation de cellules souches hématopoïétiques/méthodes , Immunothérapie adoptive/méthodes , Enfant , Leucémies/thérapie , Leucémies/immunologie , Cellules dendritiques/immunologie , Mâle , Enfant d'âge préscolaire , Femelle , Adolescent , Donneurs de tissus , Greffe haplo-identique/méthodes
11.
Front Immunol ; 15: 1354992, 2024.
Article de Anglais | MEDLINE | ID: mdl-38736891

RÉSUMÉ

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.


Sujet(s)
Marqueurs biologiques tumoraux , Antigènes CD44 , Leucémies , Cellules souches tumorales , Humains , Cellules souches tumorales/métabolisme , Cellules souches tumorales/immunologie , Antigènes CD44/métabolisme , Leucémies/métabolisme , Leucémies/thérapie , Leucémies/immunologie , Marqueurs biologiques tumoraux/métabolisme , Animaux , Transduction du signal , Thérapie moléculaire ciblée
16.
Front Immunol ; 15: 1382099, 2024.
Article de Anglais | MEDLINE | ID: mdl-38665912

RÉSUMÉ

Introduction: Chimerism is closely correlated with disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, chimerism rate is dynamic changes, and the sensitivity of different chimerism requires further research. Methods: To investigate the predictive value of distinct chimerism for relapse, we measured bone marrow (BM), peripheral blood (PB), and T-cell (isolated from BM) chimerism in 178 patients after allo-HSCT. Results: Receiver operating characteristic (ROC) curve showed that T-cell chimerism was more suitable to predict relapse after allo-HSCT compared with PB and BM chimerism. The cutoff value of T-cell chimerism for predicting relapse was 99.45%. Leukemia and myelodysplastic syndrome (MDS) relapse patients' T-cell chimerism was a gradual decline from 2 months to 9 months after allo-HSCT. Higher risk of relapse and death within 1 year after allo-HSCT. The T-cell chimerism rates in remission and relapse patients were 99.43% and 94.28% at 3 months after allo-HSCT (P = 0.009), 99.31% and 95.27% at 6 months after allo-HSCT (P = 0.013), and 99.26% and 91.32% at 9 months after allo-HSCT (P = 0.024), respectively. There was a significant difference (P = 0.036) for T-cell chimerism between early relapse (relapse within 9 months after allo-HSCT) and late relapse (relapse after 9 months after allo-HSCT) at 2 months after allo-HSCT. Every 1% increase in T-cell chimerism, the hazard ratio for disease relapse was 0.967 (95% CI: 0.948-0.987, P<0.001). Discussion: We recommend constant monitoring T-cell chimerism at 2, 3, 6, and 9 months after allo-HSCT to predict relapse.


Sujet(s)
Chimérisme , Transplantation de cellules souches hématopoïétiques , Leucémies , Syndromes myélodysplasiques , Lymphocytes T , Lymphocytes T/anatomopathologie , Transplantation homologue , Récidive , Moelle osseuse , Leucémies/diagnostic , Leucémies/thérapie , Syndromes myélodysplasiques/diagnostic , Syndromes myélodysplasiques/thérapie , Humains , Mâle , Femelle , Adolescent , Jeune adulte , Adulte , Adulte d'âge moyen , Sujet âgé
17.
Noise Health ; 26(120): 25-29, 2024.
Article de Anglais | MEDLINE | ID: mdl-38570307

RÉSUMÉ

OBJECTIVE: To explore the effects of music nursing as a complementary therapy on anxiety, fatigue, and quality of life in children with acute leukemia (AL). METHODS: This study included 150 children with AL admitted to our hospital from August 2021 to August 2023 and divided them into two groups based on treatment: the control (n = 76, received routine nursing) and observation (n = 74, received music nursing on the basis of routine nursing) groups. Comparison of groups was performed in terms of general information, anxiety, fatigue, and quality of life at admission (T0) and 1 month after admission (T1). RESULTS: No significant differences were observed in the general data between the two groups (P > 0.05). Anxiety, fatigue, and quality of life of the two groups also showed no significant differences at T0 (P > 0.05). The observation group showed significantly lower anxiety than the control group at T1 (P < 0.05). At T1, the observation group exhibited a lower fatigue degree compared with the control group (P < 0.05). At T1, the observation group attained higher scores on physiological and emotional dimensions of the quality of life compared with the control group, and the differences were statistically significant (P < 0.05). CONCLUSION: Music nursing for AL children, which has a certain clinical application value, can effectively reduce their anxiety and fatigue and improve their quality of life.


Sujet(s)
Thérapies complémentaires , Leucémies , Musicothérapie , Musique , Enfant , Humains , Qualité de vie/psychologie , Études rétrospectives , Anxiété/étiologie , Anxiété/thérapie , Leucémies/thérapie , Musicothérapie/méthodes , Fatigue/étiologie , Fatigue/thérapie
18.
Cancer Res Commun ; 4(5): 1253-1267, 2024 May 13.
Article de Anglais | MEDLINE | ID: mdl-38592213

RÉSUMÉ

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling. Following 14 days ex vivo expansion with zoledronic acid and IL2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro and in vivo in leukemia-bearing xenogeneic mice. Infusing humans with the ß1+ß2-agonist isoproterenol and administering ß1 or ß1+ß2 antagonists prior to exercise revealed these effects to be ß2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced antileukemic effects of exercise. These findings provide a mechanistic link between exercise, ß2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematologic malignancies. SIGNIFICANCE: Exercise mobilizes effector γδ T-cells to blood via ß2-adrenergic signaling which allows for generation of a potent expanded γδ T-cell product that is highly cytotoxic against hematologic malignancies.


Sujet(s)
Antigènes de différenciation des lymphocytes T , Exercice physique , Récepteurs bêta-2 adrénergiques , Régulation positive , Animaux , Humains , Mâle , Souris , Antigènes de différenciation des lymphocytes T/métabolisme , Molécules d'adhérence cellulaire/métabolisme , Lignée cellulaire tumorale , Exercice physique/physiologie , Leucémies/immunologie , Leucémies/thérapie , Récepteurs bêta-2 adrénergiques/métabolisme , Récepteur lymphocytaire T antigène, gamma-delta/métabolisme , Tests d'activité antitumorale sur modèle de xénogreffe
19.
N Engl J Med ; 390(16): 1467-1480, 2024 Apr 25.
Article de Anglais | MEDLINE | ID: mdl-38657244

RÉSUMÉ

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).


Sujet(s)
Maladie du greffon contre l'hôte , Transplantation de cellules souches hématopoïétiques , Immunothérapie adoptive , Leucémies , Lymphomes , Récepteurs chimériques pour l'antigène , Adolescent , Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Antigènes CD7 , Association thérapeutique , Maladie du greffon contre l'hôte/prévention et contrôle , Transplantation de cellules souches hématopoïétiques/effets indésirables , Transplantation de cellules souches hématopoïétiques/méthodes , Immunothérapie adoptive/effets indésirables , Immunothérapie adoptive/méthodes , Leucémies/thérapie , Leucémies/mortalité , Lymphomes/mortalité , Lymphomes/thérapie , Récepteurs chimériques pour l'antigène/usage thérapeutique , Induction de rémission , Transplantation homologue , Récidive , Sujet âgé
20.
Transplant Cell Ther ; 30(7): 692.e1-692.e12, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38643958

RÉSUMÉ

The clinical value of serial routine bone marrow aspirates (rBMAs) in the first year after allogeneic hematopoietic cell transplantation (alloHCT) to detect or predict relapse of acute leukemia (AL) and myelodysplastic syndrome (MDS) in pediatric and young adult patients is unclear. The purpose of this analysis was to determine if assessment of minimal residual disease (MRD) by multiparameter flow cytometry (MFC, MFC-MRD) or donor chimerism (DC) in rBMAs or serial complete blood counts (CBCs) done in the year after alloHCT predicted relapse of AL or MDS in pediatric and young adult patients. We completed a retrospective analysis of patients with AL or MDS who had rBMAs performed after alloHCT between January 2012 and June 2018. Bone marrow (BM) was evaluated at approximately 3, 6, and 12 months for disease recurrence by morphology, MFC-MRD, and percent DC by short tandem repeat molecular testing. CBCs were performed at every clinic visit. The main outcome of interest was an assessment of whether MFC-MRD or DC in rBMAs or serial CBCs done in the year after alloHCT predicted relapse in AL or MDS pediatric and young adult patients. A total of 121 recipients with a median age of 13 years (range 1 to 32) were included: 108 with AL and, 13 with MDS. A total of 423 rBMAs (median 3; 0 to 13) were performed. Relapse at 2 years was 23% (95% CI: 16% to 31%) and at 5 years 25% (95% CI: 18% to 33%). One hundred fifty-four of 157 (98%) rBMAs evaluated for MRD by MFC were negative and did not preclude subsequent relapse. Additionally, low DC (<95%) did not predict relapse and high DC (≥95%) did not preclude relapse. For patients alive without relapse at 1 year, BM DC (P = .74) and peripheral T-cell DC (P = .93) did not predict relapse. Six patients with low-level T-cell and/or BM DC had a total of 8 to 20 BM evaluations, none of these patients relapsed. However, CBC results were informative for relapse; 28 of 31 (90%) relapse patients presented with an abnormal CBC with peripheral blood (PB) blasts (16 patients), cytopenias (9 patients), or extramedullary disease (EMD, 3 patients). Two patients with BM blasts >5% on rBMA had circulating blasts within 5 weeks of rBMA. Neutropenia (ANC <1.5 K/mcl) at 1 year was predictive of relapse (P = .01). Neutropenia and thrombocytopenia (<160 K/mcl) were predictive of disease-free survival (DFS) with inferior DFS for ANC <1.5 K/mcl, P = .001, or platelet count <160 K/mcl (P = .04). These results demonstrate rBMAs after alloHCT assessed for MRD by MFC and/or for level of DC are poor predictors for relapse in pediatric and young adult patients with AL or MDS. Relapse in these patients presents with PB blasts, cytopenias, or EMD. ANC and platelet count at 1-year were highly predictive for DFS.


Sujet(s)
Transplantation de cellules souches hématopoïétiques , Syndromes myélodysplasiques , Récidive , Humains , Syndromes myélodysplasiques/thérapie , Enfant , Mâle , Adolescent , Femelle , Jeune adulte , Adulte , Enfant d'âge préscolaire , Études rétrospectives , Moelle osseuse/anatomopathologie , Maladie résiduelle , Leucémies/thérapie , Nourrisson , Maladie aigüe ,
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