Total Skin Treatment with Helical Arc Radiotherapy.

For widespread cutaneous lymphoma, such as mycosis fungoides or leukemia cutis, in patients with acute myeloid leukemia (AML) and for chronic myeloproliferative diseases, total skin irradiation is an efficient treatment modality for disease control. Total skin irradiation aims to homogeneously irradiate the skin of the entire body. However, the natural geometric shape and skin folding of the human body pose challenges to treatment. This article introduces treatment techniques and the evolution of total skin irradiation. Articles on total skin irradiation by helical tomotherapy and the advantages of total skin irradiation by helical tomotherapy are reviewed. Differences among each treatment technique and treatment advantages are compared. Adverse treatment effects and clinical care during irradiation and possible dose regimens are mentioned for future prospects of total skin irradiation.

Family caregivers' itineraries of preschool children who survived leukemia: implications for primary healthcare nursing.

OBJECTIVES: to analyze the path taken by family caregivers of preschool children who survived leukemia and discuss the implications for primary healthcare nursing. METHODS: the narrative interview guided by a talking map and body knowledge was used with family members of children who survived leukemia, living in Rio de Janeiro (capital) and São Paulo (countryside). Conversation analysis was applied to the data. RESULTS: five family groups (seven people) of five children started their journey in the professional subsystem of private services; four were assisted in the private sector since the onset of the illness; one was assisted in public and private services. Living conditions reduced barriers to accessing supplementary health, facilitating coordination, and listening to a reference professional. FINAL CONSIDERATIONS: the itinerary was marked by attentive listening to family caregivers by reference professionals, favoring early diagnosis, initiation of treatment, and resolution of leukemia with the cure of children.

The Promising Role of Non-Coding RNAs as Biomarkers and Therapeutic Targets for Leukemia.

Early-stage leukemia identification is crucial for effective disease management and leads to an improvement in the survival of leukemia patients. Approaches based on cutting-edge biomarkers with excellent accuracy in body liquids provide patients with the possibility of early diagnosis with high sensitivity and specificity. Non-coding RNAs have recently received a great deal of interest as possible biomarkers in leukemia due to their participation in crucial oncogenic processes such as proliferation, differentiation, invasion, apoptosis, and their availability in body fluids. Recent studies have revealed a strong correlation between leukemia and the deregulated non-coding RNAs. On this basis, these RNAs are also great therapeutic targets. Based on these advantages, we tried to review the role of non-coding RNAs in leukemia. Here, the significance of several non-coding RNA types in leukemia is highlighted, and their potential roles as diagnostic, prognostic, and therapeutic targets are covered.

A Novel Form of Arginine-Chitosan as Nanoparticles Efficient for siRNA Delivery into Mouse Leukemia Cells.

The modification of chitosan (CS) has greatly expanded its application in the field of medicine. In this study, low-molecular-weight chitosan was modified with arginine (Arg) by a simple method. The identification by the Fourier transform infrared spectra (FTIR) showed that Arg was successfully covalently attached to the CS. Interestingly, Arg-CS was identified as nanoparticles by atomic force microscopy (AFM) and transmission electron microscopy (TEM), whose particle size was 75.76 ± 12.07 nm based on Dynamic Light Scattering (DLS) characterization. Then, whether the prepared Arg-CS nanoparticles could encapsulate and deliver siRNA safely was investigated. Arg-CS was found to be able to encapsulate siRNAs in vitro via electrostatic interaction with siRNA; the Arg-CS/siRNA complex was safe for L1210 leukemia cells. Therefore, modification of chitosan by Arg produces novel nanoparticles to deliver siRNA into leukemia cells. This is the first time to identify Arg-CS as nanoparticles and explore their ability to deliver Rhoa siRNA into T-cell acute lymphoblastic leukemia (T-ALL) cells to advance therapies targeting Rhoa in the future.

Never forsake-The positive experiences of dyadic coping among patients with acute leukemia and their spouses: A qualitative study.

PURPOSE: This study aimed to explore the positive experiences of dyadic coping between patients with acute leukemia and their spouses in China, and to highlight the target factors that could promote coping and adaptation. METHODS: A qualitative descriptive study was employed. This study was conducted at a tertiary hospital in China from September 2021 to February 2022. A purposive sampling method was used to select participants, and 17 patients diagnosed with acute leukemia and their spouses were interviewed. Qualitative data were analyzed using the content analysis method. This study followed the COREQ checklist. RESULTS: This study's data were categorized into five themes and twelve subthemes: (1) adapting to a new role-couples used role adjustments to adapt; (2) commitment to companionship-patients benefit from spousal commitment in word or in deed; (3) active communication-allows couples to get to know each other better; (4) white lies-shield partner from negative information; (5) seeking external support-outside of couple cohesion. In sum, positive dyadic coping experiences between couples follow the marital commitment of "never forsake." CONCLUSIONS: This study contributes new knowledge to the understanding of the dyadic coping experiences of patients with acute leukemia and their spouses within the Chinese social-cultural context and contributes to cross-cultural comparisons. The results can be used to design and implement couple-based intervention programs to support couples by enhancing their mutual support to cope with and adjust to acute leukemia effectively.

Evaluation of the Effectiveness of a Technology-Based Psychosocial Education and Counseling Program for Adolescent Survivors of Childhood Leukemia: A Randomized Controlled Trial.

BACKGROUND: In addition to increased survivorship in childhood leukemia, a small but significant number of survivors experience psychosocial challenges that affect their health-related quality of life (QOL) that require interventions to address these challenges. OBJECTIVE: The aim of this study was to evaluate the efficacy of the technology-based, psychosocial education and counseling program on survivors' QOL, self-efficacy, and coping skills within the scope of a health promotion model for adolescent survivors of childhood leukemia. METHODS: The randomized controlled trial was conducted with adolescent survivors of childhood leukemia who were between the ages of 12 and 18 and had completed treatment at least 2 years previously. Survivors were randomized to a technology-based intervention (n = 24) or a control group (n = 31). Survivors' QOL, self-efficacy, and coping skills were measured at 4 time points (baseline, postintervention, 1 month postintervention, and 3 months postintervention). RESULTS: The 3-month postintervention QOL total and psychosocial subscale scores in the intervention group were significantly higher than those in the control group ( P < .05). In addition, the emotional self-efficacy subscale scores and the active coping scores of the intervention group adolescents were significantly higher than those in the control group ( P < .05). Negative coping scores were lower in the intervention group than in the control group ( P < .05). CONCLUSION: Technology-based, psychosocial counseling and education positively affects the QOL, emotional self-efficacy, and coping skills of adolescent survivors of childhood leukemia. IMPLICATIONS FOR PRACTICE: This program could be integrated into follow-up care and used as one of the support methods in providing and maintaining long-term follow-up care by pediatric oncology nurses.

Gene therapy in a murine model of chronic eosinophilic leukemia-not otherwise specified (CEL-NOS).

Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare, aggressive, fatal disease characterized by blood eosinophilia and dysfunction of organs infiltrated with eosinophils. Clinically, the disease manifests with weight loss, cough, weakness, diarrhea, and multi-organ dysfunction that is unresponsive to therapy. We developed a one-time gene therapy for CEL-NOS using an adeno-associated virus (AAV) expressing an anti-eosinophil monoclonal antibody (AAVrh.10mAnti-Eos) to provide sustained suppression of eosinophil numbers in blood, thus reducing eosinophil tissue invasion and organ dysfunction. A novel CEL-NOS model was developed in NOD-scid IL2rγnull (NSG) mice by administration of AAV expressing the cytokine IL5 (AAVrh.10mIL5), resulting in marked peripheral and tissue eosinophilia of the heart, lung, liver, and spleen, and eventually death. Mice were administered AAVrh.10mAnti-Eos (1011 genome copies) 4 wk after administration of AAVrh.10mIL5 and evaluated for anti-eosinophil antibody expression, blood eosinophil counts, organ eosinophil invasion, and survival. AAVrh.10mAnti-Eos expressed persistent levels of the anti-eosinophil antibody for >24 wk. Strikingly, CEL-NOS treated mice had markedly lower blood eosinophil levels and reduced mortality when compared with control treated mice. These results suggest that a single treatment with AAVrh.10mAnti-Eos has the potential to provide substantial therapeutic benefit to patients with CEL-NOS, a fatal malignant disorder.

A novel costimulatory molecule gene-modified leukemia cell-derived exosome-targeted CD4+ T cell vaccine efficiently enhances anti-leukemia immunity.

Previous studies demonstrated that CD4+ T cells can uptake tumor antigen-pulsed dendritic cell-derived exosomes (DEXO), which harbor tumor antigen peptide/pMHC I complex and costimulatory molecules and show potent effects on inducing antitumor immunity. However, in preliminary study, CD4+ T cells targeted by leukemia cell-derived exosomes (LEXs) did not show the expected effects in inducing effective anti-leukemia immunity, indicating that LEX is poorly immunogenetic largely due to an inadequate costimulatory capacity. Therefore, LEX-based anti-leukemia vaccines need to be optimized. In this study, we constructed a novel LEX-based vaccine by combining CD4+ T cells with costimulatory molecules gene-modified LEXs, which harbor upregulated CD80 and CD86, and the anti-leukemia immunity of CD80 and CD86 gene-modified LEX-targeted CD4+ T cells was investigated. We used lentiviral vectors encoding CD80 and CD86 to successfully transduced the L1210 leukemia cells, and the expression of CD80 and CD86 was remarkably upregulated in leukemia cells. The LEXs highly expressing CD80 and CD86 were obtained from the supernatants of gene-transduced leukemia cells. Our data have shown that LEX-CD8086 could promote CD4+ T cell proliferation and Th1 cytokine secretion more efficiently than control LEXs. Moreover, CD4+ TLEX-CD8086 expressed the acquired exosomal costimulatory molecules. With acquired costimulatory molecules, CD4+ TLEX-CD8086 can act as APCs and are capable of directly stimulating the leukemia cell antigen-specific CD8+ CTL response. This response was higher in potency compared to that noted by the other formulations. Furthermore, the animal study revealed that the CD4+ TLEX-CD8086 significantly inhibited tumor growth and prolonged survival of tumor-bearing mice than other formulations did in both protective and therapeutic models. In conclusion, this study revealed that CD4+ TLEX-CD8086 could effectively induce more potential anti-leukemia immunity than LEX-CD8086 alone, suggesting that the utilization of a costimulatory molecule gene-modified leukemia cell-derived exosome-targeted CD4+ T cell vaccine may have promising potential for leukemia immunotherapy.

[The role of CRISPR screening in leukemia research].

Recent advances in comprehensive genome analysis have contributed to the discovery of several leukemia-related genes; however, the role of mutated genes in the pathogenesis of leukemia remains unknown. Clustered regularly interspaced short palindromic repeats-associated nuclease 9 (CRISPR-Cas9) technology is a powerful tool for genome-wide editing in both coding and noncoding regions. CRISPR screening has enabled high-throughput validation of gene function in diverse tumor processes, including tumor growth and survival, synthetic lethal interactions, therapeutic resistance, and response to immunotherapy, and is actively used in leukemia research. Herein, we discuss recent advances in CRISPR screening in cancer research, focusing on leukemia, and outline application strategies and prospects for CRISPR screening.

Type I interferon subtypes differentially activate the anti-leukaemic function of natural killer cells.

Natural killer (NK) cells have an intrinsic ability to detect and eliminate leukaemic cells. Cellular therapies using cytokine-activated NK cells have emerged as promising treatments for patients with advanced leukaemia. However, not all patients respond to current NK cell therapies, and thus improvements in efficacy are required. Type I interferons (IFN-I) are a family of potent immunomodulatory cytokines with a known ability to modulate NK cell responses against cancer. Although the human IFN-I family comprises 16 distinct subtypes, only IFNα2 has been widely explored as an anti-cancer agent. Here, we investigated the individual immunomodulatory effects each IFNα subtype and IFNß had on NK cell functionality to determine whether a particular subtype confers enhanced effector activity against leukaemia. Importantly, IFNα14 and IFNß were identified as superior activators of NK cell effector function in vitro. To test the ability of these subtypes to enhance NK cell activity in vivo, IFN-I stimulation was overlaid onto a standard ex vivo expansion protocol to generate NK cells for adoptive cell therapy. Interestingly, infusion of NK cells pre-activated with IFNα14, but not IFNß, significantly prolonged survival in a preclinical model of leukaemia compared to NK cells expanded without IFN-I. Collectively, these results highlight the diverse immunomodulatory potencies of individual IFN-I subtypes and support further investigation into the use of IFNα14 to favourably modulate NK cells against leukaemia.

Label-free testing strategy to evaluate packed red blood cell quality before transfusion to leukemia patients.

Patients worldwide require therapeutic transfusions of packed red blood cells (pRBCs), which is applied to the high-risk patients who need periodic transfusions due to leukemia, lymphoma, myeloma and other blood diseases or disorders. Contrary to the general hospital population where the transfusions are carried out mainly for healthy trauma patients, in case of high-risk patients the proper quality of pRBCs is crucial. This leads to an increased demand for efficient technology providing information on the pRBCs alterations deteriorating their quality. Here we present the design of an innovative, label-free, noninvasive, rapid Raman spectroscopy-based method for pRBCs quality evaluation, starting with the description of sample measurement and data analysis, through correlation of spectroscopic results with reference techniques' outcomes, and finishing with methodology verification and its application in clinical conditions. We have shown that Raman spectra collected from the pRBCs supernatant mixture with a proper chemometric analysis conducted for a minimum one ratio of integral intensities of the chosen Raman marker bands within the spectrum allow evaluation of the pRBC quality in a rapid, noninvasive, and free-label manner, without unsealing the pRBCs bag. Subsequently, spectroscopic data were compared with predefined reference values, either from pRBCs expiration or those defining the pRBCs quality, allowing to assess their utility for transfusion to patients with acute myeloid leukemia (AML) and lymphoblastic leukemia (ALL).

The psychological, psychosocial and emotional wellbeing of children and young people with leukaemia.

BACKGROUND: Leukaemia is the most common childhood cancer, and with the success of current treatment, it has an overall survival rate of up to 92%. Despite this, treatment does not come without consequences. As a result, it is no surprise that recent research has examined the long-term implications of this treatment. METHODS: An integrative review was conducted to capture a broad range of primary research studies from both quantitative and qualitative perspectives. Four electronic databases were searched, displaying 3239 articles, of which nine met all the inclusion criteria. This integrative review explores these studies, using thematic analysis, with the purpose of identifying the impact this disease has on the psychological, psychosocial and emotional wellbeing of children and young people (CYP) diagnosed with leukaemia. RESULTS: The review highlighted the vast impact that a leukaemia diagnosis can have on CYP and five main trends emerged: experienced emotions; relationships with peers; relationships with family; academic challenges; and differentiating factors. DISCUSSION: As a result of the findings, it is recommended that CYP receive psychological support from diagnosis, with a regular reassessment throughout treatment. Parents and carers require support to enable them to efficiently care for their children. It is evident from this review that further research in this area would be beneficial to address some gaps in the literature.

Traumatic stress symptoms in family caregivers of patients with acute leukaemia: protocol for a multisite mixed methods, longitudinal, observational study.

INTRODUCTION: The diagnosis, progression or recurrence of cancer is often highly traumatic for family caregivers (FCs), but systematic assessments of distress and approaches for its prevention and treatment are lacking. Acute leukaemia (AL) is a life-threatening cancer of the blood, which most often presents acutely, requires intensive treatment and is associated with severe physical symptoms. Consequently, traumatic stress may be common in the FCs of patients with AL. We aim to determine the prevalence, severity, longitudinal course and predictors of traumatic stress symptoms in FCs of patients with AL in the first year after diagnosis, and to understand their lived experience of traumatic stress and perceived support needs. METHODS AND ANALYSIS: This two-site longitudinal, observational, mixed methods study will recruit 223 adult FCs of paediatric or adult patients newly diagnosed with AL from two tertiary care centres. Quantitative data will be collected from self-report questionnaires at enrolment, and 1, 3, 6, 9 and 12 months after admission to hospital for initial treatment. Quantitative data will be analysed using descriptive and machine learning approaches and a multilevel modelling (MLM) approach will be used to confirm machine learning findings. Semi-structured qualitative interviews will be conducted at 3, 6 and 12 months and analysed using a grounded theory approach. ETHICS AND DISSEMINATION: This study is funded by the Canadian Institutes of Health Research (CIHR number PJT 173255) and has received ethical approval from the Ontario Cancer Research Ethics Board (CTO Project ID: 2104). The data generated have the potential to inform the development of targeted psychosocial interventions for traumatic stress, which is a public health priority for high-risk populations such as FCs of patients with haematological malignancies. An integrated and end-of-study knowledge translation strategy that involves FCs and other stakeholders will be used to interpret and disseminate study results.

Qualitative Analysis of the Roles of Physicians and Nurses in Providing Decision Support to Patients With Relapsed or Refractory Leukemia and Lymphoma.

INTRODUCTION: This study examined the roles of hematologists and other professionals in providing decision support to patients with relapsed or refractory leukemia and lymphoma. METHODS: This was a qualitative study using in-depth semi-structured interviews involving 11 hematologists in Japan. RESULT: We identified 7 categories related to the roles of hematologists in providing direct decision support to patients: (1) preparing patients before informed consent, (2) selecting the information to convey, (3) choosing a method for conveying this information, (4) respecting the intentions of patients and their families, (5) directing decision-making and considering fairness, (6) considering the emotional aspects of patients and their families, and (7) providing support after discussing treatment options. We also identified the following 5 subcategories related to the roles of hematologists in multidisciplinary collaboration: (1) communicating with other professionals, (2) gathering information from them, (3) providing information to them, (4) managing the entire medical team, and (5) encouraging nurses to actively participate with patients throughout the decision-making process. CONCLUSION: Through content analysis, the hematologist's direct role in decision-making was extracted as preparation and consideration in situations where information about decision-making is communicated, and emotional support after the information is communicated. In addition, active participation in discussions, sharing information about the patient's situation and relevant discussions, and emotional support as the hematologist's expected roles in other professions were extracted. The results therefore suggest that a multidisciplinary team is needed to share information and provide multidimensional support to patients.

[Knowledge and practice of patient-derived xenograft models in leukemia].

Patient-derived xenograft (PDX) models have gained attention due to their wide applications in basic research and drug development, and due to the increase in requirements for pathological analysis and anticancer drug evaluation. The development of immunodeficient mouse strains with high-level engraftment of normal and diseased cells has contributed to the considerable progress in understanding the human pathophysiology. The PDX model is one of the most important tools to bridge the gap between traditional animal models and the clinical trials. PDX not only recapitulates human disease in vivo, but also multiplies the tumor cells. Therefore, efforts were made internationally to develop a PDX bank for leukemias and solid tumors for future research and experimentation. PDX might be an ideal model to simulate actual human diseases for cancer research; however, some challenges still persist. Thus, this review aimed to summarize the developmental history of immune-deficient mice, the efforts of overcoming PDX limitations, PDX model applications for preclinical research, and the current attempts to establish domestic leukemia PDX bank in Japan.

Comparison of Predator-Prey Model and Hawk-Dove Game for Modelling Leukemia.

Game theory is an excellent mathematical tool to describe the interaction between the immune system and cancerous leukocytes (c.leu). The feature of cancerous leukocytes to differentiate and mutate to give rise to leukemia is in the domain of ecological models as well. In this work, the dynamic of leukemia is described and compared by two models: firstly by a simple probabilistic mathematical model using the zero-sum two player game of Hawk and Dove, and secondly by Leslie Predator Prey model of ecology. The main goal of this study is to compare the results of both models and then discuss the treatment of leukemia i.e., Hematopoietic Stem cell transplant with the best model among them. Hawk and Dove model also describes the cell to cell interaction of cancerous leukocytes and healthy leukocytes (leu) after diagnoses and the condition of the patient before and after treatments. In this work, Hematopoietic Stem cell transplant is discussed by using concepts of a zero-sum three player game. Also, both models will be characterized by determining the stability properties, identifying basins of attraction, and locating the equilibrium points to see, at what extent the patient's survival is possible with leukemia in its body. Results for both models will be presented graphically.

Sphingolipid metabolism in T cell responses after allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy against hematopoietic malignancies. The infused donor lymphocytes attack malignant cells and normal tissues, termed a graft-verse-leukemia (GVL) effect and graft-verse-host (GVH) response or disease (GVHD), respectively. Although engineering techniques toward donor graft selection have made HCT more specific and effective, primary tumor relapse and GVHD are still major concerns post allo-HCT. High-dose systemic steroids remain to be the first line of GVHD treatment, which may lead to steroid-refractory GVHD with a dismal outcome. Therefore, identifying novel therapeutic strategies that prevent GVHD while preserving GVL activity is highly warranted. Sphingolipid metabolism and metabolites play pivotal roles in regulating T-cell homeostasis and biological functions. In this review, we summarized the recent research progress in this evolving field of sphingolipids with a focus on alloreactive T-cell responses in the context of allo-HCT. We discussed how sphingolipid metabolism regulates T-cell mediated GVH and GVL responses in allo-HCT and presented the rationale and means to target sphingolipid metabolism for the control of GVHD and leukemia relapse.