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Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial.

ABSTRACT: Gut mucosal barrier injury is common following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and associated with poor clinical outcomes. Diet is critical for microbial diversity, but whether nutritional support affects microbiota and outcome after allo-HSCT is unknown. We present a secondary analysis of a randomized controlled nutritional intervention trial during allo-HSCT. We investigated if the intervention influenced gut microbiota, short-chain fatty acids (SCFAs), and markers of gut barrier functions, and if these parameters were associated with clinical outcomes. Fecal specimens were available from 47 recipients, and subjected to 16S rRNA gene sequencing. We found no significant differences between the intervention group and controls in investigated parameters. We observed a major depletion of microbiota, SCFAs, and altered markers of gut barrier function from baseline to 3 weeks post-transplant. One-year mortality was significantly higher in patients with lower diversity at 3 weeks post-HSCT, but not related to diversity at baseline. The relative abundance of Blautia genus at 3 weeks was higher in survivors. Fecal propionic acid was associated with survival. Markers of gut barrier functions were less strongly associated with clinical outcomes. Possibly, other strategies than dietary intervention are needed to prevent negative effects of gut microbiota and clinical outcomes after allo-HSCT.ClinicalTrials.gov (NCT01181076).

SUBMITTER: Skaarud KJ

PROVIDER: S-EPMC8172574 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesThis study aimed to describe the impact of allogeneic/haploidentical hematopoietic stem cell transplantation on nutritional status and intake in a group of children aged 2 to 18 years.MethodsIn an observational study, data were collected prospectively. Patients were prescribed individual nutritional support by hospital routines. Anthropometrics were measured pre-transplant at hospital admission and weekly from the day of transplant (day 0) until day +28. z scores for weight, height, and BMI were calculated using Norwegian growth references to assess nutritional status. Pre-transplant diet was assessed on the day of hospitalization. Nutrient provision from enteral nutrition (EN = oral and tube) and parenteral nutrition (PN) was assessed by daily records from day +1 until day +28, or previous discharge, and compared with recommendations (RI) from the Nordic Nutrition Recommendations and ESPGHAN guidelines. Total energy intake was presented as the percentage (%) of basal metabolic rate (BMR) calculated by the Schofield equation. Macro- and micronutrient provisions were presented as medians (interquartile range) and the % of RI.ResultsTwenty-eight patients, mean age 10.3 years (range 3.5-16.6), were included. Two-thirds (n = 18) had malignant diseases. At admission, mean weight Z-score was -0.3, height z scores -0.7, and BMI Z-score 0.1. Eighteen percent (n = 5) were stunted and 25% (n = 7) had overweight. At admission, 25% (n = 7) had established tube feeding, and 7% (n = 2) also had PN. No significant changes in weight z scores were detected during the studied weeks ( P = 0.454). The median daily energy provision was 115% (110-123) of BMR and proteins 1.5 (1.3-1.8) g/kg. EN was provided during a median of 93% of the studied days and provided 21% of the energy. PN was given on a median of 96% of the studied days and provided 79% of energy. RI for vitamins, magnesium, and zinc was met. Provision of copper, iodine, selenium, calcium, and phosphate was below RI.ConclusionsCombined EN and PN providing 115% of BMR and 1.5 g/kg protein ensured stable weight by day +28 and covered RI, except for trace elements and minerals.

Project description:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for many patients with hematological malignancies and nonmalignant hematopoietic disorders. To achieve stable engraftment of donor hematopoietic stem cells (HSCs), recipient HSC deletion is needed to create space for incoming donor HSCs and donor HSCs must escape immune rejection by the recipient. Conventional allo-HSCT requires high dose of irradiation and/or chemotherapy to produce sufficient host stem cell and immune system ablation to permit donor HSC engraftment. However, these procedures also result in nonspecific tissue injury that can cause short- and long-term adverse effects as well as incite and amplify graft-versus-host-disease (GVHD). The delivery of targeted radiotherapy to hematopoietic tissues with the use of a radioimmunoconjugate (ROIC) as a part of transplant preparative regimen has shown clinical benefits. ROIC clinical data provide evidence for decreased relapse without increased transplant-related mortality by delivering higher targeted radiation to sites of malignancy than when given in a nontargeted fashion. An alternative approach to allo-HSCT has been developed and tested in preclinical mouse models in which nonmyeloablative preconditioning with low dose of the alkylating agent (busulfan) or lower systemic dose of irradiation combined with co-stimulatory pathway blockade (CTLA4-Ig, anti-CD40L monoclonal antibody) and/or immunosuppressive drugs have been used. Under these conditions, mixed chimerism and transplantation tolerance to fully MHC mismatched donor marrow was observed. Recently, several novel proof-of-concept antibody-mediated preconditioning methods have been developed that can selectively target hematopoietic stem and immune cells with minimal overall toxicity. Antibody-drug-conjugate (ADC) combined with reduced intensity conditioning or high dose ADC as single dose monotherapy have shown promise for allo-HSCT in preclinical models. The purpose of the current review is to discuss the literature exploring antibody-based conditioning that includes native antibody, radiolabeled antibody conjugates, and ADC for allo-HSCT.

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Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial.

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