-
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.
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.
-
3.
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.
-
4.
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.
-
5.
Intravenous Vitamin C Supplementation in Allogeneic Hematopoietic Cell Transplant Recipients: Salutary Impact on Clinical Outcomes
Toor, A., Simmons, G., Sabo, R., Aziz, M., Martin, E., Bernard, R., Sripa, M., McIntire, C., Kreiger, E., Brophy, D., et al
Research square. 2023
Abstract
Intravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (HCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic HCT were evaluated in a phase I/II trial. Clinical outcomes were compared with a propensity score - matched historical control. Methods: Patients with advanced hematologic malignancies received IV vitamin C, 50mg/kg/d, divided into 3 doses given on days 1-14 after HCT, followed by 500 mg bid oral from day 15 until 6 months post-SCT. Results 55 patients received IV vitamin C. All patients were deficient in vitamin C at day 0. Vitamin C recipients had lower non-relapse mortality (NRM) (p = 0.07) and improved survival compared to historical controls (p=0.06), with no attributable grade 3 and 4 toxicities. Vitamin C recipients had similar relapse rate and acute graft versus host disease (GVHD) (p=0.35), but lower severe chronic GVHD (p=0.35). Patients with myeloid malignancies had improved survival (p=0.02) and NRM (p=0.009), as well as chronic GVHD, with similar relapse rates compared to controls. Conclusions: In patients undergoing allogeneic HCT the administration of IV vitamin C is safe and reduces non-relapse mortality and chronic GVHD improving overall survival.
-
6.
Comparison of three malnutrition screening tools prior to allogeneic hematopoietic stem-cell transplantation
Khosroshahi, R. A., Mohammadi, H., Barkhordar, M., Zeraattalab-Motlagh, S., Imani, H., Rashidi, A., Sadeghi, E., Wilkins, S., Mousavi, S. A.
Frontiers in nutrition. 2023;10:1233074
Abstract
BACKGROUND Previous studies have shown that malnutrition before hematopoietic stem cell transplantation (HSCT) is associated with poor patient prognoses. There is inconsistency among studies on which nutritional status screening tool is appropriate for malnutrition diagnosis before allo-HSCT. The present study aimed to compare nutritional screening tools in patients with leukemia before allo-HSCT. METHODS An observational, cross-sectional, and single-center study was conducted in Tehran, Iran. One hundred four adults allo-HSCT candidates aged 18-55 years with leukemia were selected sequentially. Malnutrition assessment was done using three tools, the Global Leadership Initiative on Malnutrition (GLIM), nutritional risk screening 2002 (NRS-2002) and European Society for Clinical Nutrition and Metabolism (ESPEN) criteria. The agreement between malnutrition assessment tools was evaluated with Cohen's kappa. RESULTS The agreement between GLIM and NRS-2002 was perfect (κ = 0.817, p < 0.001), while the agreement between GLIM and ESPEN was fair (κ = 0.362, p < 0.001). The agreement between NRS-2002 and ESPEN was fair (κ = 0.262, p < 0.001). We also found a moderate agreement for all tools (κ = 0.489, p < 0.001). CONCLUSION NRS-2002 is an accepted tool for screening malnutrition in hospitalized patients. In the current study, the GLIM criterion perfectly agreed with the NRS-2002. Further studies in the HSCT setting are needed to introduce a valid tool.
-
7.
[Nutritional evolution during the early stages of hematopoietic stem cell transplantation: importance of the phase angle]
Valdés Boccardo, S., Sarmiento Maldonado, M., Velasco Fuentes, N.
Nutricion hospitalaria. 2023
Abstract
INTRODUCTION the aim of this study is to compare the changes in anthropometry, dynamometry and bioelectrical impedance analysis (BIA) of patients undergoing autologous and allogeneic hematopoietic stem cell transplantation (HSCT) after the conditioning period and one-week post-transplantation, and to assess whether these early changes are associated with the development of later complications. METHODS prospective cohort study. Nutritional status was assessed by anthropometry, dynamometry and BIA at three different defined times: T1, time of admission; T2, after the myeloablative conditioning period; and T3, day + 8 post-HSCT. RESULTS forty patients were evaluated, 17 received autologous HSCT (TAU) and 23 received allogeneic HSCT (TAL). Patients with TAL had higher mortality and hospital stay compared to patients with TAU. Those who developed graft versus host disease (GVHD) presented a lower phase angle (PA) than those who did not develop this complication (T2: TAL PA with GVHD 4.8° vs TAL PA without GVHD 5.5°, p = 0.007). The patients who died during the hospital stay are all from the TAL group and had PA less than 5° at T3. Weight, body mass index (BMI) and fat-free mass index (FMI) did not show a significant impact, and all of them were influenced by total body water. CONCLUSIONS early nutritional evaluation of these patients by phase angle seems promising, since it is not altered by water retention and can be evaluated before anthropometric changes occur.
-
8.
Optimized Vitamin D Repletion in Refractory Patients Undergoing Stem Cell Transplant with Oral Thin Film Cholecalciferol
Bartlett, A. L., Zhang, G., Wallace, G., McLean, S., Myers, K. C., Teusink-Cross, A., Taggart, C., Patel, B., Davidson, R., Davies, S. M., et al
Blood advances. 2023
Abstract
Vitamin D deficiency is common in childhood, pervasive before and after bone marrow transplant, and associated with increased incidence of graft-versus-host disease (GVHD) and decreased survival in patients undergoing hematopoietic stem cell transplantation (HSCT). Numerous barriers impede replacement, including malabsorption secondary to gut GVHD, mucositis, inability to take capsules, kidney disease, liver disease, and infection; many patients remain refractory despite vitamin D therapy. We hypothesized that a different formulation of cholecalciferol, administered on the tongue as a readily dissolving oral thin film (OTF), would ease administration and facilitate therapeutic vitamin D levels (>35 ng/mL) in refractory patients. In this prospective pilot study, we evaluated 20 patients post-HSCT (range: day +21 - day +428 at enrollment) with serum vitamin D levels ≤35 ng/mL. Cholecalciferol OTF strips (CURE Pharmaceutical) were administered for twelve weeks. Dosing was based on patient size and titrated according to individual pharmacokinetics. Wilcoxon matched-pairs signed rank test demonstrated marked improvement in all 20 formerly refractory patients, increasing from a median baseline vitamin D of 29.2 ng/mL to 58 ng/mL at end of study (p<0.0001). All patients demonstrated improvement in serum vitamin D level by week 4 on study, some of whom had been refractory for years prior. Median dose was 1 OTF strip (40,000 IU) per week. No toxicity was observed. This formulation proved to be safe, effective, efficient, and well-received. We are eager to explore other patient populations which might benefit from this promising development, and other therapeutics which might be optimized by this mode of delivery.
-
9.
Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study
Mizutani, Y., Kawamoto, S., Takahashi, M., Doi, H., Wakida, K., Tabuchi, S., Tanda, M., Soga, A., Chijiki, R., Takakura, H., et al
Internal medicine (Tokyo, Japan). 2023
Abstract
Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.
-
10.
Loading dose vitamin D3 improves vitamin D insufficiency in adults undergoing hematopoietic stem cell transplantation: A randomized controlled trial
Bai, N., Lee, K., Limvorapitak, W., Liu, E., Kendler, D., Broady, R., White, J.
PloS one. 2023;18(10):e0284644
Abstract
Allogeneic hematopoietic stem cell transplant (aHSCT) patients are well known to be at high risk of vitamin D (vit D) deficiency. This study assessed whether a loading dose (100,000 IU) of vitamin D3 pre-aHSCT could effectively achieve and maintain sufficient post-transplant vit D levels (serum total 25 hydroxy vitamin D (25(OH)D) ≥ 75nmol/L). Dual-energy X-ray absorptiometry (DXA) was also conducted for bone health evaluation. 74 patients were enrolled and randomly assigned, in a 1:1 ratio, either to the high vit D group (single loading dose (100,000 IU) plus 2,000 IU vit D3 daily) or the control group (2,000 IU vit D3 daily). Vit D levels were measured at three time points (baseline, day 30 and day 100 post-aHSCT). At baseline, fewer than 50% patients had a sufficient 25(OH)D (control: 42.9%; high vit D: 43.6%). The proportion of patients with sufficient 25(OH)D (nmol/L) was increased at day 30 and day 100, with a trend of higher proportion in the high vit D group at day 30 (high vit D vs. control: 89.7% vs. 74.3%, p = 0.08). The increased 25(OH)D was significantly higher in the high vit D group at day 30 (high vit D vs. control: 29±25.2 vs. 14 ±21.9, p = 0.01). Insufficient vit D level before transplant (baseline) was an independent risk factor for vit D insufficiency (serum 25(OH)D < 75nmol/L) post-aHSCT (OR = 4.16, p = 0.03). DXA suggested significant bone loss for total hip in both groups, and in the femoral neck for the control group only. In conclusion, single loading dose vitamin D3 significantly increased total 25(OH)D levels at day 30 post-transplant, and the intervention was especially beneficial for patients with baseline vit D insufficiency. We acknowledge that the primary outcome at day 100 post-aHSCT indicating superiority of loading dose versus daily dose supplementation was not met.