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BACKGROUND: Triokinase and FMN cyclase (TKFC) is a bifunctional enzyme involved in fructose metabolism. Triokinase catalyses the phosphorylation of fructose-derived glyceraldehyde (GA) and exogenous dihydroxyacetone (DHA), while FMN cyclase generates cyclic FMN. TKFC regulates the antiviral immune response by interacting with IFIH1 (MDA5). Previously reported pathogenic variants in TKFC are associated with either a multisystemic disease or isolated hypotrichosis with loose anagen hairs. METHODS: Whole-exome sequencing identified a homozygous novel variant in TKFC (c.1624G>A; p.Gly542Arg) in an individual with a complex primary immunodeficiency disorder. The variant was characterised using enzymatic assays and yeast studies of mutant recombinant proteins. RESULTS: The individual presented with chronic active Epstein-Barr virus disease and multiple bacterial and viral infections. Clinical investigations revealed hypogammaglobulinaemia, near absent natural killer cells and decreased memory B cells. Enzymatic assays showed that this variant displayed defective DHA and GA kinase activity while maintaining FMN cyclase activity. An allogenic bone marrow transplantation corrected the patient's immunodeficiency. CONCLUSION: Our report suggests that TKFC may have a role in the immunological system. The pathological features associated with this variant are possibly linked with DHA/GA kinase inactivation through a yet an unknown mechanism. This report thus adds a possible new pathway of immunometabolism to explore further.
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Homozygote , Humains , , Phosphotransferases (Alcohol Group Acceptor)/génétique , Mâle , Infections à virus Epstein-Barr/génétique , Infections à virus Epstein-Barr/virologie , Infections à virus Epstein-Barr/complications , Déficits immunitaires/génétique , Déficits immunitaires/anatomopathologie , Femelle , Mutation/génétiqueRÉSUMÉ
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the standard of care for chemotherapy-refractory leukemia patients, but cure rates are still dismal. To prevent leukemia relapse following HSCT, we aim to improve the early graft-versus-leukemia effect mediated by natural killer (NK) cells. Our approach is based on the adoptive transfer of Therapeutic Inducers of Natural Killer cell Killing (ThINKK). ThINKK are expanded and differentiated from HSC, and exhibit blood plasmacytoid dendritic cell (pDC) features. We previously demonstrated that ThINKK stimulate NK cells and control acute lymphoblastic leukemia (ALL) development in a preclinical mouse model of HSCT for ALL. Here, we assessed the cellular identity of ThINKK and investigated their potential to activate allogeneic T cells. We finally evaluated the effect of immunosuppressive drugs on ThINKK-NK cell interaction. METHODS: ThINKK cellular identity was explored using single-cell RNA sequencing and flow cytometry. Their T-cell activating potential was investigated by coculture of allogeneic T cells and antigen-presenting cells in the presence or the absence of ThINKK. A preclinical human-to-mouse xenograft model was used to evaluate the impact of ThINKK injections on graft-versus-host disease (GvHD). Finally, the effect of immunosuppressive drugs on ThINKK-induced NK cell cytotoxicity against ALL cells was tested. RESULTS: The large majority of ThINKK shared the key characteristics of canonical blood pDC, including potent type-I interferon (IFN) production following Toll-like receptor stimulation. A minor subset expressed some, although not all, markers of other dendritic cell populations. Importantly, while ThINKK were not killed by allogeneic T or NK cells, they did not increase T cell proliferation induced by antigen-presenting cells nor worsened GvHD in vivo. Finally, tacrolimus, sirolimus or mycophenolate did not decrease ThINKK-induced NK cell activation and cytotoxicity. CONCLUSION: Our results indicate that ThINKK are type I IFN producing cells with low T cell activation capacity. Therefore, ThINKK adoptive immunotherapy is not expected to increase the risk of GvHD after allogeneic HSCT. Furthermore, our data predict that the use of tacrolimus, sirolimus or mycophenolate as anti-GvHD prophylaxis regimen will not decrease ThINKK therapeutic efficacy. Collectively, these preclinical data support the testing of ThINKK immunotherapy in a phase I clinical trial.
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Transplantation de cellules souches hématopoïétiques , Cellules tueuses naturelles , Cellules tueuses naturelles/immunologie , Cellules tueuses naturelles/métabolisme , Cellules tueuses naturelles/effets des médicaments et des substances chimiques , Humains , Transplantation de cellules souches hématopoïétiques/méthodes , Animaux , Souris , Transplantation homologue , Cellules dendritiques/immunologie , Cellules dendritiques/métabolisme , Femelle , Maladie du greffon contre l'hôte/prévention et contrôleRÉSUMÉ
A recent measure was developed to assess the Quality of Life (QoL) of young people with advanced cancer and is available for parents and professionals (Advance QoL). The present study aimed to elaborate self-reported versions for children and adolescents with advanced cancer. We adopted a four-phase research plan: (1) to elaborate the Advance QoL questionnaire for youth (8-12 and 13-18 years old) with a team of young research partners; (2) to evaluate the understandability of these versions in a sample of 12 young patients from the target population using cognitive interviews; (3) to assess social validity in the same group using a questionnaire and the content validity index (CVI); and (4) to refine the questionnaires according to these results. Four major themes were identified: (1) issues affecting the understanding of the tool; (2) issues that did not affect the understanding of the tool; (3) modifications to improve the tool; and (4) positive features of the tool. Advance QoL was well received, and feedback was positive. Adjustments were made according to young people's comments and two self-reported versions are now available. It is essential to measure the key domains of QoL in advanced cancer. Advance QoL self-report versions will help target the specific needs of young people with this condition and their families.
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Tumeurs , Mesures des résultats rapportés par les patients , Qualité de vie , Humains , Qualité de vie/psychologie , Adolescent , Enfant , Tumeurs/psychologie , Mâle , Femelle , Enquêtes et questionnaires , AutorapportRÉSUMÉ
ABSTRACT: Acute megakaryoblastic leukemia (AMKL) is a rare, developmentally restricted, and highly lethal cancer of early childhood. The paucity and hypocellularity (due to myelofibrosis) of primary patient samples hamper the discovery of cell- and genotype-specific treatments. AMKL is driven by mutually exclusive chimeric fusion oncogenes in two-thirds of the cases, with CBFA2T3::GLIS2 (CG2) and NUP98 fusions (NUP98r) representing the highest-fatality subgroups. We established CD34+ cord blood-derived CG2 models (n = 6) that sustain serial transplantation and recapitulate human leukemia regarding immunophenotype, leukemia-initiating cell frequencies, comutational landscape, and gene expression signature, with distinct upregulation of the prosurvival factor B-cell lymphoma 2 (BCL2). Cell membrane proteomic analyses highlighted CG2 surface markers preferentially expressed on leukemic cells compared with CD34+ cells (eg, NCAM1 and CD151). AMKL differentiation block in the mega-erythroid progenitor space was confirmed by single-cell profiling. Although CG2 cells were rather resistant to BCL2 genetic knockdown or selective pharmacological inhibition with venetoclax, they were vulnerable to strategies that target the megakaryocytic prosurvival factor BCL-XL (BCL2L1), including in vitro and in vivo treatment with BCL2/BCL-XL/BCL-W inhibitor navitoclax and DT2216, a selective BCL-XL proteolysis-targeting chimera degrader developed to limit thrombocytopenia in patients. NUP98r AMKL were also sensitive to BCL-XL inhibition but not the NUP98r monocytic leukemia, pointing to a lineage-specific dependency. Navitoclax or DT2216 treatment in combination with low-dose cytarabine further reduced leukemic burden in mice. This work extends the cellular and molecular diversity set of human AMKL models and uncovers BCL-XL as a therapeutic vulnerability in CG2 and NUP98r AMKL.
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Antinéoplasiques , Leucémie aigüe mégacaryoblastique , Humains , Enfant , Enfant d'âge préscolaire , Animaux , Souris , Leucémie aigüe mégacaryoblastique/traitement médicamenteux , Leucémie aigüe mégacaryoblastique/génétique , Leucémie aigüe mégacaryoblastique/anatomopathologie , Protéomique , Facteurs de transcription , Protéines proto-oncogènes c-bcl-2 , Protéines de répressionRÉSUMÉ
Objectives: This study reports cases of systemic-onset juvenile idiopathic arthritis (sJIA) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center and reviews published outcomes of allo-HSCT in sJIA. Methods: We present a case report of two patients with sJIA who underwent allo-HSCT at a tertiary pediatric hospital. Each patient's disease course and allo-HSCT protocol/outcome are described. Outcomes of published cases of allo-HSCT in sJIA were compared to our experience. Results: Two patients with sJIA had allo-HSCT. Both failed multiple lines of disease-modifying anti-rheumatic drugs and experienced severe disease/treatment-related complications. Despite post-HSCT complications, both recovered without sequelae. Five years post-HSCT, patient 1 is in complete remission (CR) and is off medications. Patient 2 was in CR until 11 months post-HSCT after which he developed three disease flares. At 4 years post-HSCT he is currently in CR on Adalimumab monotherapy. Engraftment was excellent with a donor chimerism of 100% for patient 1 and 93% for patient 2. In the literature, the outcome of allo-HSCT is reported in 13 sJIA patients. When merging those with our 2 patients, 1/15 patients died and 13/14 achieved CR, of which 12 are off medications (median [range] follow-up: 2.2 [0.2-7.0] years). Extended follow-up data on 11 of the 13 reported sJIA patients showed that an additional 3 patients flared at 3, 4, and 10 years post-HSCT. Conclusion: We report two patients with severe/refractory sJIA who underwent successful allo-HSCT and achieved CR. Allo-HSCT is a potential curative option for severe/refractory sJIA. It should be considered only after failure of conventional sJIA treatments and when an HLA-matched donor is available in order to lower transplant-related mortality. The outcomes of reported sJIA patients who received allo-HSCT are encouraging but long-term follow-up data are needed to better characterized the risk-benefit ratio of this procedure.
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Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram's anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.
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Disulfirame , Neuroblastome , Animaux , Enfant , Humains , Souris , Substances à effet antabuse/pharmacologie , Substances à effet antabuse/usage thérapeutique , Lignée cellulaire tumorale , Disulfirame/pharmacologie , Disulfirame/usage thérapeutique , Régulation négative , Repositionnement des médicaments , Émulsions/usage thérapeutique , Histone acetyltransferases/effets des médicaments et des substances chimiques , Neuroblastome/traitement médicamenteux , Neuroblastome/génétiqueRÉSUMÉ
CONTEXT: There is no universal definition of cancer-related fatigue (CRF) specific to childhood cancer survivors, despite this population facing unique long-term side effects from their cancer. We aimed to synthesize and combine existing definitions of CRF specific to this context to inform on the necessity of a panel of experts to formulate a new definition of CRF for childhood cancer survivors. METHODS: The literature search was performed in various databases. Titles, abstracts, and keywords were screened by two researchers to confirm eligibility. The data extraction process was performed by two researchers. Our search was conducted in various databases. RESULTS: Thirty articles were included in the qualitative analysis. Two coders reached consensus on 14 codes. The thematization process produced 4 themes: frequency, context, attributes, and consequences of CRF. These themes were used to synthesize a definition of CRF, as follows: "In childhood cancer survivors, cancer-related fatigue is a common late effect of cancer and cancer treatments. It is characterized by a subjective, persistent, and multidimensional experience that differs from normal fatigue in the physical, emotional, and/or cognitive spheres. Cancer-related fatigue may have a variety of negative consequences including a reduced quality of life and level of functioning, a lack of vigor, work difficulties, relationship issues, and emotional distress." CONCLUSION: A definition of CRF applicable to childhood cancer survivors is timely to organize research efforts and design appropriate interventions. The proposed definition is a first step towards the formulation of a new definition of CRF specific to childhood cancer survivors by experts.
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Survivants du cancer , Tumeurs , Humains , Enfant , Survivants du cancer/psychologie , Tumeurs/complications , Tumeurs/psychologie , Qualité de vie/psychologie , Fatigue/thérapie , ÉmotionsRÉSUMÉ
Introduction: Studies in pediatric oncology have shown that hypnosis effectively reduces patients' pain and distress during painful procedures. This remains underutilized in the healthcare system due to the staff cost and availability of hypnotherapists. To develop the use of hypnosis-derived communication, we aimed to train nurses to use hypnosis-derived communication while they perform painful procedures. Objectives: This study aimed to (1) develop a brief training in hypnosis-derived communication for pediatric nurses named Rel@x, (2) pretest the training with experienced pediatric oncology nurses, and (3) refine the training based on nurses' suggestions. Methods: The Rel@x training consists of two 4-h sessions: one related to relational aspects and another one presenting one of two selected hypnotic communication techniques ("pleasant place" or "magic glove"). Rel@x makes use of manuals, cue card reminders, visual aids, videos, and an e-learning platform. To refine Rel@x, a complete training cycle was conducted with seven female pediatric oncology nurses. A mixed method study with an evaluation questionnaire and a post-training focus group interview was conducted. Results: Quantitative data showed that nurses overall positively rated the training program: relevance and acceptability (median average of 5.4/6); use of hypnotic communication (median average of 5.2/6); expected effects (median average of 5.4/6); program implementation (5.6/6). Two general themes emerged from the qualitative data: perceptions of hypnotic communication and the evaluation of the Rel@x training program. Based on nurses' suggestions, Rel@x was refined by adding more practical components, more time for practice, more time between the two sessions and additional tools (cue card reminders, keywords, virtual e-learning recap module). Conclusion and clinical implications: The use of hypnosis-derived communication during painful procedures and the Rel@x training were viewed favorably amongst pediatric nurses. Rel@x offers a complete training in hypnosis-derived communication for pediatric nurses. This training fosters the optimal use of hypnosis-derived communication during care and may significantly reduce children's procedural pain and distress.
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OBJECTIVES: We aimed to identify contributors to cancer-related fatigue (CRF), explore non-pharmacological interventions addressing CRF, and highlight which contributors were targeted by these interventions in childhood cancer survivors. METHODS: We performed a search in various databases and used the PRISMA-ScR checklist. Findings were synthesized in various different tables and figures in accordance with our objectives. RESULTS: We included 49 articles in this systematic scoping review. We identified 59 significant contributors. Depression and physical activity level were some of the most studied significant contributors. Ten interventional studies were identified (e.g., yoga, physical activity intervention) that addressed 6 contributors (e.g., physical activity level). DISCUSSION: This review is the first to describe and relate contributors and non-pharmacological interventions targeting CRF in childhood cancer survivors. Important clinical implications could be derived from the variety of factors explaining CRF and how it is currently addressed.
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Survivants du cancer , Tumeurs , Yoga , Enfant , Fatigue/étiologie , Fatigue/thérapie , Humains , Tumeurs/complications , Tumeurs/thérapie , Qualité de vieRÉSUMÉ
BACKGROUND: Advanced childhood cancer, a condition with no available cancer-focused treatment options, greatly impacts Quality of Life (QoL). We need appropriate assessment strategies to select adapted treatment targets, improve care and optimize communication. Our first goal was to identify the domains of patients' QoL by combining for the first time the perspectives of patients and parents with previously collected reports in professionals. Our second goal was to develop a simple QoL assessment tool and optimize its format and content for use in the childhood advanced cancer population. METHODS: To identify QoL domains, we conducted qualitative interviews with 7 young patients (4 girls, 3 boys, aged 13 ± 4 yrs) and 9 parents (7 mothers, 2 fathers) from our treatment centre. We used inductive thematic content analysis to code and categorize respondents' viewpoints. The first version of the tool (Advance QoL) was then drafted, and structured feedback was collected through interviews and a survey with 15 experts. We computed content validity indices. RESULTS: Apart from the physical, psychological, and social domains, participants insisted on four original themes: autonomy, pleasure, the pursuit of achievement, and the sense of feeling heard. This was in line with the categories found in a preliminary study involving professionals (PMID: 28137343). Experts evaluated the tool as clear, relevant, acceptable, and usable. They formulated recommendations on instructions, timeframe, and item formulations, which we implemented in the refined version. CONCLUSIONS: Advance QoL is an innovative tool targeting key life domains in childhood advanced cancer. It is focused on preserved abilities and targets of care. The refined version is appropriate for adult respondents within families and professionals. Future studies will develop versions for young ages to collect the experience of patients themselves. This will open on future reliability, validity, sensitivity, and implementation studies.
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Tumeurs/psychologie , Qualité de vie , Adolescent , Adulte , Enfant , Formation de concepts , Femelle , Humains , Mâle , Tumeurs/thérapie , Reproductibilité des résultats , Enquêtes et questionnairesRÉSUMÉ
In the hospital milieu, daily questions relate to highly invested areas such as quality of life and death issues, choices to continue or stop active treatment, and the legitimacy of those who take part in such decisions. Stemming from an ethnographic study carried out in a hematology-oncology transplant unit in a Montreal pediatric hospital, we discuss the decision-making process (or lack thereof) when a patient faces poor prognosis and the change of trajectory from a curative/disease directed to a palliative perspective. The intricate relationship between science, caregiver, and care receiver sustains action even when (near) death is the probable outcome.
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Prise de décision , Qualité de vie , Anthropologie médicale , Aidants , Enfant , Humains , Soins palliatifsRÉSUMÉ
Grieving a child following cancer is a substantially difficult task. The objectives of this research were: 1) to describe current quality of life (QoL), psychological distress and symptoms of grief of bereaved parents, and 2) to explore the role of possible contributors of QoL and psychological distress. Forty-six parents (32 mothers) of children who died of cancer were surveyed on their QoL, distress, and complicated grief. Data were analyzed using multiple linear regression. Parents had a high frequency of grieving symptoms (58%). Mothers reported more retrospective grief symptoms than fathers when describing the year after child death. Current lower mental well-being was associated with experiencing higher retrospective grief symptoms, a shorter period since child death, and being a father. Hence, parents experienced disturbances even long after child death. Mothers and fathers may present specificities that should be considered when developing supportive activities for this vulnerable population.
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Tumeurs , Qualité de vie , Adaptation psychologique , Enfant , Mort , Femelle , Chagrin , Humains , Parents/psychologie , Études rétrospectives , AutorapportRÉSUMÉ
Posttransplant leukemia detection before overt relapse is key to the success of immunotherapeutic interventions, as they are more efficient when leukemia burden is low. However, optimal schedule and monitoring methods are not well defined. We report the intensive bone marrow monitoring of minimal residual disease (MRD) using flow cytometry (FC) and nested reverse transcription polymerase chain reaction (RT-PCR) whenever a fusion transcript allowed it and chimerism by PCR at 11 timepoints in the first 2 years after transplant. Seventy-one transplants were performed in 59 consecutive children, for acute myeloid (n = 38), lymphoid (n = 31), or mixed-phenotype (n = 2) leukemia. MRD was monitored in 62 cases using FC (n = 58) and/or RT-PCR (n = 35). Sixty-seven percent of leukemia recurrences were detected before overt relapse, with a detection rate of 89% by RT-PCR and 40% by FC alone. Increased mixed chimerism was never the first evidence of recurrence. Two patients monitored by RT-PCR relapsed without previous MRD detection, one after missed scheduled evaluation and the other 4.7 years post transplant. Among the 22 cases with MRD detection without overt relapse, 19 received therapeutic interventions. Eight (42%) never relapsed. In conclusion, intensive marrow monitoring by RT-PCR effectively allows for early detection of posttransplant leukemia recurrence.
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Transplantation de cellules souches hématopoïétiques , Leucémie aigüe myéloïde , Chimérisme , Transplantation de cellules souches hématopoïétiques/méthodes , Humains , Leucémie aigüe myéloïde/génétique , Leucémie aigüe myéloïde/thérapie , Maladie résiduelle/diagnostic , Maladie résiduelle/génétique , Récidive , Transplantation homologueRÉSUMÉ
OBJECTIVE: This scoping review will aim to identify the domains contributing to cancer-related fatigue in childhood cancer survivors and will explore whether non-pharmacological interventions have addressed these domains. This information will help to better define cancer-related fatigue, identify knowledge gaps in the literature, and direct future research efforts. INTRODUCTION: Cancer-related fatigue is a commonly reported symptom in aftercare following childhood cancer treatments. However, its operational definition and contributors are unclear, which makes it difficult to select targets and design adequate interventions. In this scoping review, we will identify contributing domains to help clarify their role as key characteristics of cancer-related fatigue. We will then review the evidence as to whether these contributing domains have been addressed by non-pharmacological interventions aimed at fatigue. INCLUSION CRITERIA: We will include articles on cancer-related fatigue following childhood cancer treatments (age at diagnosis ≤ 21 years) and non-pharmacological interventions aimed at reducing fatigue. Both will retain qualitative and quantitative studies will be considered for inclusion. METHODS: In accordance with the JBI methodological framework for conducting scoping reviews, we will perform a search in PubMed, PsycINFO, CINAHL, Embase, Cochrane Library, Grey Matters, OAlster, and OpenGrey. We will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist. Studies published in English or French will be included, with no date limitations. The data collection and analysis of eligible articles will be performed by two independent reviewers and will be classified in summary tables. The findings on contributors to cancer-related fatigue in childhood cancer survivors will be synthesized in a cross table linking contributor domains with intervention type.
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Survivants du cancer , Tumeurs , Enfant , Fatigue/étiologie , Humains , Tumeurs/complications , Plan de recherche , Littérature de revue comme sujet , Revues systématiques comme sujetRÉSUMÉ
BACKGROUND: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections can have serious consequences during the period of aplasia and lymphopenia following hematopoietic stem cell transplantation (HSCT). Large pediatric cohort studies examining the effect of antiviral prophylaxis against these viruses are scarce. The present study aimed to analyse the potential effect of antiviral prophylaxis (acyclovir and famciclovir) on active post-transplant EBV and CMV infection in a pediatric cohort of allogeneic HSCT recipients. METHODS: We used data from the TREASuRE cohort, consisting of 156 patients who had a first allogeneic HSCT, enrolled in four pediatric centers in Canada between July 2013 and March 2017. Follow-up was performed from the time of transplant up to 100 days post-transplant. Adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the association between antiviral prophylaxis with acyclovir and/or famciclovir and EBV and CMV DNAemia was estimated using multivariate Cox regression models. RESULTS: The post-transplant cumulative incidence of EBV and CMV DNAemia at 100 days of follow-up were, respectively, 34.5% (95% CI: 27.6-42.6) and 19.9% (95% CI: 14.5-27.1). For acyclovir, the adjusted hazard ratio (HR) for CMV and EBV DNAemia was 0.55 (95% CI: 0.24-1.26) and 1.41 (95% CI: 0.63-3.14), respectively. For famciclovir, the adjusted HR were 0.82 (95% CI: 0.30-2.29) and 0.79 (95% CI: 0.36-1.72) for CMV and EBV DNAemia, respectively. CONCLUSION: The antivirals famciclovir and acyclovir did not reduce the risk of post-transplant CMV and EBV DNAemia among HSCT recipients in our pediatric population.
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BACKGROUND: Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. METHODS: We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. RESULTS: Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). CONCLUSION: This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.
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Infections à virus Epstein-Barr/épidémiologie , Transplantation de cellules souches hématopoïétiques , Canada/épidémiologie , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Immunosuppresseurs/usage thérapeutique , Nourrisson , Syndromes lymphoprolifératifs/épidémiologie , Mâle , Études prospectives , Facteurs de risque , Facteurs sexuelsRÉSUMÉ
OBJECTIVES: To explore the effects of a hypnotic communication (HC) training for paediatric nurses in decreasing patients' pain and distress during venipunctures. METHODS: A 4-day theoretical and practical HC training was offered to five paediatric oncology nurses. The effects of HC were tested with 22 young cancer patients (13 girls, 9 boys, 10 ± 4 years) over four time points, with 88 encounters being video-recorded and coded in stable professional-patient dyads. Patients' pain and distress were rated by patients and parents with visual analogue scales and coded from recordings using the Faces, Legs, Activity, Cry and Consolability (FLACC) scale. RESULTS: We observed a significant decrease in pre-post distress reported by parents (d = 0.45, p = 0.046). Two out of five nurses with higher skills acquisition had larger reduction in patients' self-reported pain (d = 1.03, p = 0.028), parents perceived pain (d = 1.09, p = 0.042), distress (d = 1.05, p = 0.043) as well as observed pain (d = 1.22, p = 0.025). Favourable results on pain and distress did not maintain at follow-up. CONCLUSION AND CLINICAL IMPLICATIONS: Training nurses in HC may translate into improved pain and distress in patients, both self-rated and observed provided that skills are used in practice. HC training is a promising non-pharmacological intervention to address pain in paediatrics.
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Umbilical cord blood transplantation (UCBT) has been used to treat malignant and non-malignant diseases. UCBT offers the advantages of easy procurement and acceptable partial HLA mismatches, but also shows delayed hematopoietic and immunological recoveries. We postulated that an intrabone (IB) infusion of cord blood could provide a faster short- and long-term engraftment in a pediatric population with malignant and non-malignant hematologic diseases. We conducted this phase I-II single arm, exploratory clinical trial (NCT01711788) from 2012 to 2016 in a single center. Fifteen patients aged from 1.9 to 16.4 years received an IB UCBT. Median time to neutrophils and platelet recoveries were 18 days (range: 13-36 days) and 42 days (range: 26-107 days), respectively. Rate of severe acute GVH grade was low, with only one patient with grade III aGVH. Relapse occurred in 5 patients (38.5%) and TRM occurred in 1 patient. This leads to 6 years EFS and OS of 66.7% and 80% respectively. In conclusion, IB UCBT is safe and well-tolerated in children and hematological recovery compared similarly to the results obtained with IV UCBT.
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Transplantation de cellules souches de sang du cordon , Maladie du greffon contre l'hôte , Transplantation de cellules souches hématopoïétiques , Enfant , Sang foetal , Humains , Récidive tumorale localeRÉSUMÉ
This systematic review was undertaken to identify risk factors associated with post-transplant Epstein-Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92-9.45) and 4.17 (95% CI: 2.61-6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.