-
1.
Effects of Korean red ginseng on T-cell repopulation after autologous hematopoietic stem cell transplantation in childhood cancer patients
Hong, K. T., Kang, Y. J., Choi, J. Y., Yun, Y. J., Chang, I. M., Shin, H. Y., Kang, H. J., Lee, W. W.
Journal of ginseng research. 2024;48(1):68-76
Abstract
BACKGROUND Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. METHODS This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. RESULTS All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4(+) T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4(+) EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28(-) subset was ameliorated. CONCLUSIONS These findings suggest that KRG promotes the repopulation of CD4(+) EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.
-
2.
A randomized phase 2 trial of oral vitamin A for graft-versus-host disease in children and young adults
Khandelwal, P., Langenberg, L., Luebbering, N., Lake, K., Butcher, A., Werling, K., Ramos, K. N., Taggart, C., Choe, H. K., Vasu, S., et al
Blood. 2024
-
-
-
-
Editor's Choice
Abstract
Vitamin A plays a key role in the maintenance of gastrointestinal homeostasis and promotes a tolerogenic phenotype in tissue resident macrophages. We conducted a prospective randomized double-blinded placebo-controlled clinical trial in which 80 hematopoietic stem cell transplant recipients were randomized 1:1 to receive pre-transplant high-dose vitamin A or placebo. A single oral dose of vitamin A of 4000 I.U/kg, maximum 250,000 I.U was given prior to conditioning. Primary endpoint was incidence of acute GVHD at day+100. In an intent-to-treat analysis, incidence of acute GVHD was 12.5% in vitamin A arm and 20% in placebo (p=0.5). Incidence of acute GI GVHD was 2.5% in the vitamin A arm (p=0.09) and 12.5% in placebo at day+180. Incidence of chronic GVHD was 5% in the vitamin A arm and 15% in placebo (p=0.02) at 1 year. In an "as treated" analysis, cumulative incidence of acute GI GVHD at day+180 was 0% in vitamin A recipients and 12.5% in placebo (p=0.02) and chronic GVHD incidence 2.7% in the vitamin A recipients and 15% in placebo (p=0.01). The only possibly attributable toxicity was asymptomatic grade 3 hyperbilirubinemia in one vitamin A recipient at day+30, which self-resolved. Absolute CCR9+ CD8+effector memory T-cells, reflecting gut T-cell trafficking, were lower in the vitamin A arm at day+30 after HSCT (p=0.01). Levels of serum amyloid A-1, a vitamin A transport protein with pro-inflammatory effects, were lower in the vitamin A arm. The vitamin A arm had lower IL-6, IL-8, ST2 levels and likely more favorable gut microbiome and short chain fatty acids. Pre-HSCT oral vitamin A is inexpensive, has low toxicity and reduces GVHD (clinicaltrials.gov NCT03202849).
PICO Summary
Population
Children aged 12 months and over with pre transplant vitamin A levels below 75th centile of normal range for age, from a single centre in USA (n=80)
Intervention
A single oral dose of vitamin A of 4000 I.U/kg, maximum 250,000 I.U prior to conditioning pre-transplant (n=40)
Comparison
Placebo (n=40)
Outcome
In an intent-to-treat analysis, incidence of acute GVHD was 12.5% in vitamin A arm and 20% in placebo. Incidence of acute GI GVHD was 2.5% in the vitamin A arm and 12.5% in placebo at day+180. Incidence of chronic GVHD was 5% in the vitamin A arm and 15% in placebo at 1 year. In an "as treated" analysis, cumulative incidence of acute GI GVHD at day+180 was 0% in vitamin A recipients and 12.5% in placebo and chronic GVHD incidence 2.7% in the vitamin A recipients and 15% in placebo. The only possibly attributable toxicity was asymptomatic grade 3 hyperbilirubinemia in one vitamin A recipient at day+30, which self-resolved. Absolute CCR9+ CD8+effector memory T-cells, reflecting gut T-cell trafficking, were lower in the vitamin A arm at day+30 after HSCT. Levels of serum amyloid A-1, a vitamin A transport protein with pro-inflammatory effects, were lower in the vitamin A arm. The vitamin A arm had lower IL-6, IL-8, ST2 levels and likely more favorable gut microbiome and short chain fatty acids.
-
3.
The management of pain during pediatric hematopoietic stem cell transplantation: A qualitative study of contextual factors that influenced pain management practices
Plummer, K., McCarthy, M., Newall, F., Manias, E.
Pediatric blood & cancer. 2023;:e30614
Abstract
BACKGROUND Children hospitalized following hematopoietic stem cell transplantation (HSCT) experience complex and prolonged pain in response to the intensity of this treatment. OBJECTIVES To describe how pain was managed for children during HSCT therapy and how contextual factors related to the clinical environment influenced healthcare providers' and parents' pain management practices. METHODS A qualitative case study was conducted and involved semi-structured interviews at two time points following transplantation (30 and 90 days) with parents (n = 10) and naturalistic observations of pain-related care provided to children (n = 29) during HSCT therapy by their healthcare providers (n = 10). Semi-structured interviews were also conducted with healthcare providers (n = 14). RESULTS The effectiveness of pain management interventions was hindered by the multifactorial nature of pain children experienced, a gap in the provision of psychosocial interventions for pain and a lack of evidence-based guidelines for the sustained, and often long-term, administration of opioids and adjuvant medications. Misconceptions were demonstrated by healthcare providers about escalating pain management according to pain severity and differentiating between opioid tolerance and addiction. Parents were active in the management of pain for children, especially the provision of nonpharmacological interventions. Collaboration with external pain services and the impact of caring for children in protective isolation delayed timely management of pain. CONCLUSIONS There is a pressing need to create evidence-based supportive care guidelines for managing pain post transplantation to optimize children's relief from pain. If parents and children are to be involved in managing pain, greater efforts must be directed toward building their capacity to make informed decisions.
-
4.
"Their Bodies Just Give It Away": A Qualitative Study of Pain Assessment in the Context of Pediatric Hematopoietic Stem Cell Transplantation Therapy
Plummer, K. J., McCarthy, M. C., Newall, F. H., Manias, E.
Cancer nursing. 2023
Abstract
BACKGROUND Children undergoing hematopoietic stem cell transplantation (HSCT) are vulnerable to pain. OBJECTIVE This study aimed to examine how healthcare providers and parents assessed pain and what contextual factors influenced their pain assessment practices for children hospitalized after allogeneic HSCT therapy. METHODS A qualitative case study was conducted in a tertiary level pediatric HSCT unit in 2 phases. Semistructured interviews with parents were conducted at 30 and 90 days after HSCT therapy. Healthcare providers participated in naturalistic observations of pain-related care provided to children during their hospitalization for HSCT therapy and a semistructured interview. RESULTS The assessment of pain after transplantation by healthcare providers and parents was predominantly reliant on the observation of children for behaviors indicative of pain, rather than the application of validated pain assessment tools. Without formal measures of the pain experience, judgments regarding the severity of children's pain were influenced by the context of high acuity of care posttransplantation and the emotional responses of healthcare providers and parents from bearing witness to children's pain. CONCLUSION Pain assessments mostly reflected children's ability to tolerate pain, rather than a genuine measurement of how significantly pain impacted the child. IMPLICATION FOR PRACTICE This study has emphasized how the assessment of pain for children hospitalized during HSCT therapy is limited by the complexity of the clinical environment. It is recommended that validated methods of assessing pain by healthcare providers and parents be implemented into clinical practice to ensure children's pain is visible.
-
5.
Integration of daily patient-reported outcome measures in pediatric stem cell transplant
Hetzer, B., Meryk, A., Kropshofer, G., Salvador, C., Riedl, D., Lehmann, J., Rumpold, G., Haid, A., Schneeberger-Carta, V., Holzner, B., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Patients' reports of their health status are increasingly used in hematopoietic stem cell transplant (SCT) to better understand the negative impact on symptom burden and quality of life (QOL). Little is known regarding the implementation in routine clinical care, particularly how it can be used to improve supportive care. OBJECTIVES We sought to evaluate feasibility of capturing daily patient-reported outcome (PRO) in the acute phase of stem cell transplant to measure physical and psychosocial symptom burden. STUDY DESIGN In this single-center prospective observational study, we assessed daily PRO from conditioning to neutrophil engraftment in children (1-18 years of age) who underwent allogeneic or autologous SCT for malignant and non-malignant disease. The most common acute adverse effects of chemotherapy (pain, nausea, loss of appetite, sleep disturbance, and physical performance impairment) were reported daily via ePROtect, a web-based program designed to integrate health responses. RESULTS From February 2021 to March 2023, twenty children undergoing allo-SCT (n=11) or auto-SCT (n=9) and their proxies consented participation, all of them were included in this analysis. 359 PRO questionnaires were completed, corresponding to a median daily completion rate of 72.7% (IQR, 60.4-83.6). After conditioning, pain perception anticipated the rise of infectious parameters and the development of mucositis, thus initiating supportive treatment. Patients reported the strongest symptom burden at a median of 8.5 days after transplant. Four weeks after transplant, baseline values for all symptoms were restored. There were no significant differences between auto- and allo-SCT, except for nausea and loss of appetite after administration of anti-thymocyte globulin in allo-SCT CONCLUSION : This study empirically documents the daily health status of children undergoing SCT and proposes an attractive modus operandi on how continuous feedback on health-related symptoms can be integrated into daily clinical practice.
-
6.
Standardization of Pediatric Hematopoietic Stem Cell Transplant Patient Discharge to Reduce Readmission Rates
West, M., Varnes, A., Hudspeth, M.
Journal of pediatric hematology/oncology nursing. 2023;:27527530221147886
Abstract
Background: The time period after a pediatric hematopoietic stem cell transplant (P-HSCT) is tenuous as the patient is severely immunocompromised and awaiting immune reconstitution. Managing activities of daily living and medication administration after discharge from the hospital requires 24-hour care placing a heavy burden on caregivers and patients. Patients who do not adhere to the posttransplant regimen are at a higher risk for hospital readmission within the first 30 days of initial discharge with serious potential for life-threatening complications. The objective of this project was to improve 30-day readmission rates and caregiver readiness for discharge through the implementation of an evidence-based discharge protocol for P-HSCT patients and caregivers. Methods: This quality improvement project included development and implementation of comprehensive Pediatric Blood & Marrow Transplant Guidelines and discharge protocol for patients who received an inpatient autologous or allogeneic HSCT and were scheduled for discharge from a 16-bed inpatient pediatric hematology-oncology unit of a children's hospital in the southeastern United States. Readmission rates were captured through the hospital-monitored system. Results: The comprehensive discharge protocol was implemented for six patients, and 30-day readmission rates decreased from 27.29% to 3.57% following the intervention. Discussion: Results suggest the combination of an evidence-based discharge protocol with a focus on caregiver readiness for discharge and a 24-hour Rooming-In period can influence caregiver confidence and reduce 30-day readmission rates after initial discharge from a P-HSCT.
-
7.
Complications and outcomes of gastrostomy versus nasogastric tube feeding in paediatric allogeneic bone marrow transplant: A prospective cohort study
Evans, J., Green, D., Gibson, F., O'Connor, G., Lanigan, J.
Clinical nutrition ESPEN. 2023;55:58-70
Abstract
BACKGROUND & AIMS The intensive conditioning regimens administered during bone marrow transplant (BMT) frequently cause mucositis, gastrointestinal toxicity and reduced oral intake. Children are consequently at risk of malnutrition. First-line nutrition support is recommended as enteral nutrition (EN). Nasogastric tube (NGT) is the mainstay for administration. Gastrostomies provide an alternative, but there is limited evidence of their efficacy and safety in paediatric BMT. This study aimed to compare enteral tube complications and nutritional and clinical outcomes between children with a gastrostomy versus NGT throughout BMT. METHODS A prospective cohort study was conducted at a single centre in the United Kingdom. During pre-admission consultations families were offered choice of a prophylactic gastrostomy or NGT. Children undergoing allogeneic BMT were recruited from April 2021 to April 2022. Data compared between children with either tube included: tube complications, change in weight, body mass index and mid-upper-arm circumference, calorie, protein and fluid intake, timing and use of EN and parenteral nutrition, survival, graft-versus-host disease and length of admission. Following BMT, data were collected weekly for the first six weeks from electronic records, monthly thereafter from 3-day averaged food diaries and clinic assessments, until six months post-BMT. RESULTS Nineteen children with NGT were compared to 24 with a gastrostomy. Of gastrostomy complications, 94.2% (129/137) were minor, mechanical issues being most common (80/137). Dislodgement comprised 80.2% (109/136) of NGT complications. No significant differences were seen between tubes on nutritional, anthropometric and clinical outcomes. CONCLUSIONS Gastrostomies were popular with families, relatively safe, associated with mostly minor complications and similarly effective as NGTs in supporting children's nutritional intake and status. Where an NGT may not be tolerated, a prophylactic gastrostomy could be considered. Placement of either tube requires balancing their risks, benefits, the child's nutritional status, conditioning, expected duration of EN and family preferences.
-
8.
Levofloxacin prophylaxis and parenteral nutrition have a detrimental effect on intestinal microbial networks in pediatric patients undergoing HSCT
Fabbrini, M., D'Amico, F., Leardini, D., Muratore, E., Barone, M., Belotti, T., Forchielli, M. L., Zama, D., Pession, A., Prete, A., et al
Communications biology. 2023;6(1):36
Abstract
The gut microbiome (GM) has shown to influence hematopoietic stem cell transplantation (HSCT) outcome. Evidence on levofloxacin (LVX) prophylaxis usefulness before HSCT in pediatric patients is controversial and its impact on GM is poorly characterized. Post-HSCT parenteral nutrition (PN) is oftentimes the first-line nutritional support in the neutropenic phase, despite the emerging benefits of enteral nutrition (EN). In this exploratory work, we used a global-to-local networking approach to obtain a high-resolution longitudinal characterization of the GM in 30 pediatric HSCT patients receiving PN combined with LVX prophylaxis or PN alone or EN alone. By evaluating the network topology, we found that PN, especially preceded by LVX prophylaxis, resulted in a detrimental effect over the GM, with low modularity, poor cohesion, a shift in keystone species and the emergence of modules comprising several pathobionts, such as Klebsiella spp., [Ruminococcus] gnavus, Flavonifractor plautii and Enterococcus faecium. Our pilot findings on LVX prophylaxis and PN-related disruption of GM networks should be considered in patient management, to possibly facilitate prompt recovery/maintenance of a healthy and well-wired GM. However, the impact of LVX prophylaxis and nutritional support on short- to long-term post-HSCT clinical outcomes has yet to be elucidated.
-
9.
Anxiety and Depression in Parents of Children Undergoing Hematopoietic Stem Cell Transplant (HSCT)
Papasarantopoulou, A., Polikandrioti, M., Dousis, E., Evagelou, E., Zartaloudi, A., Dafogianni, C., Misouridou, E., Pavlatou, N., Mintzaridis, K., Koutelekos, I.
Advances in experimental medicine and biology. 2023;1425:31-46
Abstract
Hematopoietic stem cell transplantation (HSCT) is a well-established therapy tool for several malignant and non-malignant diseases. Parents of children undergoing HSCT experience physiological distress for various reasons such as intensive caregiving, potential complications, and medically intensive process. The purpose of this study was to explore anxiety/depression in parents of children who underwent HSCT and the associated self-reported characteristics. METHOD AND MATERIAL In the present study were enrolled 100 parents of children who underwent HSCT. Data were collected by the completion of the "Hospital Anxiety and Depression Scale (HADs)," which also included parents' characteristics. The statistical significance level was p < 0.05. RESULTS Of the 100 participants, 81% and 64% of parents experienced anxiety and depression, respectively, based on HADs scores. A statistically significant association was observed between parental anxiety and gender (p = 0.017), frequency of visiting the hospitalized child (p = 0.023), whether they desired family members to remain in hospital (p = 0.033), as well as with the need for participation in daily care (p = 0.023), for help based on personal needs (p = 0.026), for scheduled meetings with parents having same problems (p = 0.006), for contact with hospital after discharge (p = 0.035), and for written information (p = 0.044). In terms of depression, a statistically significant association was observed with difficulties during the hospital stay (p = 0.034), whether they desired other family members to remain in hospital (p = 0.009), as well as with the need for opportunities or time for questions (p = 0.004), for scheduled meetings with parents having the same problems (p = 0.026), and for contact with hospital after discharge (p = 0.038). CONCLUSION Anxiety and depression were associated with possibility of family members to remain in the hospital as well as with the need for scheduled meetings with parents having the same problems and for contact after hospital discharge. Based on the findings presented, it is suggested that understanding parents' needs and perceptions is fundamental to the development of appropriate interventions that address their worries.
-
10.
Impact of percutaneous endoscopic gastrostomy on pediatric bone marrow transplantation outcomes: Retrospectice single-center cohort study
Kairiene, I., Vaisvilas, M., Vasciunaite, A., Tubutyte, G., Nedzelskiene, I., Pasauliene, R., Muleviciene, A., Rascon, J.
JPEN. Journal of parenteral and enteral nutrition. 2023;47(3):390-398
Abstract
BACKGROUND Parenteral nutrition is commonly used to ensure nutrition support and prevent the harmful effects of malnutrition, which frequently occurs after allogeneic hematopoietic stem cell transplantation (aHSCT). Nevertheless, enteral nutrition supports the restoration of the gut barrier and microbiome as well as protects against infectious complications and acute graft-vs-host disease. Percutaneous endoscopic gastrostomy (PEG) may also be beneficial for gastric decompression and drug administration. METHODS We performed a retrospective cohort study to evaluate the impact of PEG on treatment outcomes in 75 children who underwent aHSCT with (n = 34) or without (n = 41) PEG from 2005 to 2016. RESULTS In 34 patients, PEG was used to ensure enteral nutrition support (n = 30), oral drug intake (n = 28), and abdominal decompression (n = 2). During the study period, we observed a beneficial association between PEG placement and transplant-related mortality as well as 5-year overall survival compared with the non-PEG group (12.9% vs 59.0%, P = 0.000; 85.3% vs 35.1%, P = 0.000, respectively). The beneficial impact of PEG was most prominent on 5-year overall survival in older children (12-17 years) with grafts from matched unrelated donors. CONCLUSIONS PEG placement had a positive association with transplant outcomes in pediatric patients undergoing aHSCT. To confirm these results, larger prospective studies are needed.