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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.
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2.
Hypomagnesemia May Predict Better Survival and Reduced Nonrelapse Mortality in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
Savaş, E. M., Yegin, Z. A., Kök, Mİ, Karayel, H. T., Özkurt, Z. N., Bozer, M. N., Çamoğlu, M., Gülbahar, Ö
Transplantation proceedings. 2024
Abstract
BACKGROUND Magnesium (Mg) is an essential element that is required as a cofactor for many cellular reactions, including immunologic pathways. The aim of this study was to investigate the potential impact of serum Mg levels on allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. METHODS Medical records of 340 alloHSCT recipients (median age: 45 [18-71] years; M/F: 210/130) were reviewed for this retrospective study. Serum Mg levels on days -28, -7, 0, +7, +14, +21, +30, +60, and +90 were included in the analysis. RESULTS Serum Mg(+14) levels predicted nonrelapse mortality (NRM) (P = .025) and had a significant impact on the development of mucositis (P = .027), fungal infection (P = .006), engraftment syndrome (P < .001), sinusoidal obstruction syndrome (SOS) (P = .001), cytomegalovirus (CMV) reactivation (P = .039), and acute graft vs host disease (GvHD) (P < .001). Based on the optimal threshold of serum Mg(+14) level (1.33 mg/dL; area under the curve: 0.581 [0.515-0.648]; P = .018), the study group was divided into 2 subgroups as low- and high-Mg(+14). The incidence of acute GvHD (P = .002), SOS (P = .013), engraftment syndrome (P = .013), CMV reactivation (P = .001), and Epstein Barr virus reactivation (P = .005) was significantly lower in low-Mg(+14) group. The probability of overall survival (OS) was significantly better (P = .002), whereas NRM was lower in the low-Mg(+14) group (P = .001). CONCLUSION Hypomagnesemia seems to provide a considerable advantage for the post-transplant outcome, which may confirm its potential role in the immunologic microenvironment and adaptive immunity.
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3.
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
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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.
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4.
Relevance of vitamin D in patients undergoing HLA matched allogeneic stem cell transplant for acute leukemia
Jindal, N., Saroha, M., Mirgh, S., Chichra, A., Nayak, L., Bonda, A., Gokarn, A., Punatar, S., Bagal, B., Chavan, P., et al
Transplant immunology. 2023;81:101925
Abstract
BACKGROUND In hematopoietic stem cell transplant (HSCT), vitamin D deficiency has been variably associated with increased complications, primarily graft versus host disease (GvHD), with a potential impact on survival. Results from various studies however, have not been consistent. This analysis was conducted to study the impact of peri-transplant vitamin D levels on transplant outcomes in patients with acute leukemia (AL) who underwent HLA matched (related/unrelated) HSCT. METHODS This was a single center retrospective study. Patients of AL including Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML) or Mixed Phenotypic Acute Leukemia (MPAL) who underwent fully matched or 9/10 transplants (related/unrelated) between 2008 and 2019 were included. Vitamin D deficiency was defined as serum 25-hydroxy vitamin D3 levels ≤20 ng/ml. Those with deficiency received replacement with oral vitamin D at a dose of 60,000 IU weekly for 8 weeks followed by maintenance with daily vitamin D (800 IU/day). Vitamin D levels were repeated at 4 months from start of replacement. For patients who received correction, repeat levels >20 ng/ml were considered replete. Based on vitamin D levels in the peri-transplant period (within 120 days of transplant), patients were categorised as either vitamin D replete (> 20 ng/ml) or deplete (≤ 20 ng/ml). Peri-transplant vitamin D status was correlated with transplant outcomes. RESULTS Of the 133 patients included, 31 were deplete (median vitamin D 15.0 ng/ml) and 102 were replete (median vitamin D 34 ng/ml) at time of transplant. Both groups were matched for age, diagnosis, EBMT score and disease risk index (DRI). There were no differences in time to neutrophil or platelet engraftment, CMV reactivation, acute GvHD (aGvHD) or chronic GvHD (cGvHD) between the two groups. Relapse rate, Progression Free Survival (PFS) and Overall Survival (OS) were also comparable between the 2 groups. CONCLUSION The incidence of vitamin D deficiency was high in our patient cohort. Patients who were vitamin D deficient at the time of transplant did not have inferior outcomes, suggesting a limited role of vitamin D in influencing transplant outcomes.
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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.
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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.
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7.
The prognostic value of patient-reported outcomes in allogeneic hematopoietic stem cell transplantation: exploratory analysis of a randomized nutrition intervention trial
Gudmundstuen, A. M., Efficace, F., Tjønnfjord, G. E., Skaarud, K. J., Cottone, F., Hjermstad, M. J., Iversen, P. O.
Annals of hematology. 2023
Abstract
Whether patient-reported outcomes (PROs) can predict overall survival (OS) and non-relapse mortality (NRM) among recipients of allogeneic stem cell transplantation (allo-HSCT), is unclear. We performed an exploratory analysis of the prognostic value of patient-reported outcomes (PROs) among 117 recipients of allogeneic stem cell transplantation (allo-HSCT) who participated in a randomized nutrition intervention trial. Cox proportional hazards models were used to investigate possible associations between PROs collected pre-allo-HSCT (baseline) using scores from the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) and 1-year overall survival (OS), whereas logistic regression was used to study associations between these PROs and 1-year non-relapse mortality (NRM). Multivariable analyses indicated that only the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Bone Marrow Transplantation (EBMT) risk score were associated with 1-year OS. In the multivariable model including clinical-sociodemographic factors for 1-year NRM, our analysis showed that living alone (p=0.009), HCT-CI (p=0.016), EBMT risk score (p=0.002), and stem cell source (p=0.046) could be associated with 1-year NRM. Moreover, in the multivariable model, our analysis showed that only appetite loss from the QLQ-C30 was associated with 1-year NRM (p=0.026). In conclusion, in this specific setting, our analysis suggests that the commonly used HCT-CI and EBMT risk scores could be predictive for both 1-year OS and 1-year NRM, whereas baseline PROs in general were not.
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8.
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.
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9.
Variability of contribution of 1,25 (OH)(2)D3 (vitamin D) level to hematopoietic stem cell transplantation outcome
Kamel, A. M., Radwan, E. R., Zeidan, A., Zaky, A., Ibrahim, A., Refaat, A., Abdelfattah, R., Abdelfattah, M.
Clinical nutrition ESPEN. 2023;58:355-361
Abstract
BACKGROUND The impact of vitamin D status on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) has recently been the focus of interest with a lot of controversy. In this study we aimed to evaluate the impact of pre-transplant vit. D level on the outcome of HSCT. METHODS In this study, we evaluated the impact of vitamin D level on the risk of development of graft versus host disease (GVHD) and survival after HSCT. The study included 97 patients who received allogeneic HSCT from an identical sibling. Serum vitamin D level was measured before conditioning using ELIZA. Student t-test, Mann-Whitney U test, ANOVA F-test and Kruskal-Wallis H tests were used to determine significance of difference for quantitative data. Pearson correlation, Spearman correlation and Chi-square test were used to determine correlations and associations. Kaplan-Meier and Log rank (Mantel-Cox) tests were used for analysis of survival. P value ≤ 0.05 was considered significant. RESULTS Vitamin D level showed a range of 18.24-84.6 with a mean of 38.14 ± 9.73 and a median of 36.26 ng/ml. Two patients had vitamin D level <20 and 17 had a level <30 ng/ml. Acute GVHD occurred in 33 (34 %) and chronic GVHD in 29 (29.9 %) patients. Vitamin D level had no impact on frequency or severity of GVHD; either did it impact survival. This might be attributable to the relatively normal level in the majority of our patients on account of the sunny weather of Egypt. This might also be a potential explanation for the inconsistency of the different studies with variable levels of vitamin D. CONCLUSIONS The current study failed to demonstrate an impact of pre-transplant vitamin D level on the outcome of HSCT. This might be attributed to the low prevalence of vitamin D deficiency in our population on account of our almost always sunny weather. The marked variability in the level of vitamin D that is considered sufficient interferes with objective comparison between studies; a consensus on what is considered sufficient, insufficient, or deficient is essential.
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10.
Nutritional intervention with TGF-beta enriched food for special medical purposes (TGF-FSMP) is associated with a reduction of malnutrition, acute GVHD, pneumonia and may improve overall survival in patients undergoing allogeneic hematopoietic stem transplantation
Morello, E., Brambilla, G., Bernardi, S., Villanacci, V., Carlessi, M., Farina, M., Radici, V., Samarani, E., Pellizzeri, S., Polverelli, N., et al
Transplant immunology. 2023;81:101954
Abstract
Malnutrition in allogeneic stem cell transplant (allo-SCT) is associated with poor outcomes. Supplementation with Foods for Special Medical Purposes may be a valid alternative to enteral nutrition or total parental nutrition to reduce malnutrition in allo-SCT. In this study, 133 patients consecutively allo-transplanted were assessed for nutritional status by Patient- Generated Subjective Global Assessment (PG-SGA) and supplemented with TGF-beta enriched Food for Special Medical Purposes (TGF-FSMP). PG-SGA, gold standard for nutritional assessment in oncologic patients, was assessed at admission and on day 0, +7, +14, +21, and + 28 from transplant and categorized as follows: A = good nutritional status; B = moderate malnutrition; C = severe malnutrition. TGF-FSMP (Modulen-IBD) is currently used in Inflammatory Bowel Diseases (IBD) as primary nutritional support and in this study the dose was calculated according to BMI and total daily energy expenditure (TDEE). The patients assuming ≥50% of the prescribed TGF-FSMP dose were classified in Group A; the patients who received < 50% were included in Group B per protocol. The primary endpoint of the study was the assessment of the malnourished patients in Group A and B at day+28 after transplantation, according to the criteria of PG-SGA C categorization. At day +28 after transplant: i) patients in Group A were significantly less severely malnourished than patients in the Group B (21/76,28% vs 42/53, 79% respectively, OR 2.86 - CI 1.94-4.23 -, p = 0.000); ii) the incidence of severe (MAGIC II-IV) aGVHD and of any grade gastrointestinal (GI) aGVHD was higher in Group B than in Group A, (43% vs 21% p = 0.003) and (34.5% vs 9.2% p = 0.001); iii) Pneumonia was more frequent in the malnourished patients of Group B than in well/moderate nourished patients of Group A (52.7% vs 27.6% p = 0.002). In group A parenteral nutrition was avoided more frequently than in group B (67.5% vs 33.3% p = 0.000) and a median hospital stay of 27 days in comparison to 32 was reported (p = 0.006). The estimated median overall survival (OS) of the population was 33 months in Group A and 25.1 months in group B (p = 0.03). By multivariate and ANN analysis, TGF-FSMP TR < 50% assumption was significantly correlated with malnutrition, severe and GI aGVHD, pneumonia and reduced OS.