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Metabolic Serum Profiles for Patients Receiving Allogeneic Stem Cell Transplantation: The Pretransplant Profile Differs for Patients with and without Posttransplant Capillary Leak Syndrome.

Reikvam H, Grønningsæter IS, Ahmed AB, Hatfield K, Bruserud Ø - Dis. Markers (2015)

Bottom Line: Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications.Patients with later capillary leak syndrome showed increased pretherapy levels of metabolites associated with endothelial dysfunction (homocitrulline, adenosine) altered renal regulation of fluid and/or electrolyte balance (betaine, methoxytyramine, and taurine) and altered vascular function (cytidine, adenosine, and methoxytyramine).Our observations are consistent with the hypothesis that the pretransplant metabolic status can be a marker for posttransplant abnormal fluid and/or electrolyte balance.

View Article: PubMed Central - PubMed

Affiliation: Section Hematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Section Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.

ABSTRACT
Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications. Capillary leak syndrome is a common early posttransplant complication where endothelial cell dysfunction probably contributes to the pathogenesis. In the present study we investigated whether the pretreatment serum metabolic profile reflects a risk of posttransplant capillary leak syndrome. We investigated the pretransplant serum levels of 766 metabolites for 80 consecutive allotransplant recipients. Patients with later capillary leak syndrome showed increased pretherapy levels of metabolites associated with endothelial dysfunction (homocitrulline, adenosine) altered renal regulation of fluid and/or electrolyte balance (betaine, methoxytyramine, and taurine) and altered vascular function (cytidine, adenosine, and methoxytyramine). Additional bioinformatical analyses showed that capillary leak syndrome was also associated with altered purine/pyrimidine metabolism (i.e., metabolites involved in vascular regulation and endothelial functions), aminoglycosylation (possibly important for endothelial cell functions), and eicosanoid metabolism (also involved in vascular regulation). Our observations are consistent with the hypothesis that the pretransplant metabolic status can be a marker for posttransplant abnormal fluid and/or electrolyte balance.

No MeSH data available.


Related in: MedlinePlus

Hierarchical clustering based on the cytokine profiles: a study of the first 56 consecutive patients. Based on the pretransplant cytokine levels we performed an unsupervised hierarchal clustering analysis (Euclidean distance measure with WPGMA linkage). The figure presents the heat map with corresponding dendrograms. The horizontal cytokine clustering is seen at the top of the figure and the vertical patient clustering at the left part of the figure. Red color indicates high levels and green color low levels. The right column shows the distribution of patients with capillary leak syndrome, that is, weight increase ≥5 kg marked with red bars and the others marked with green.
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fig4: Hierarchical clustering based on the cytokine profiles: a study of the first 56 consecutive patients. Based on the pretransplant cytokine levels we performed an unsupervised hierarchal clustering analysis (Euclidean distance measure with WPGMA linkage). The figure presents the heat map with corresponding dendrograms. The horizontal cytokine clustering is seen at the top of the figure and the vertical patient clustering at the left part of the figure. Red color indicates high levels and green color low levels. The right column shows the distribution of patients with capillary leak syndrome, that is, weight increase ≥5 kg marked with red bars and the others marked with green.

Mentions: Furthermore, we also performed unsupervised hierarchal clustering analyses based on the pretransplant cytokine levels. Cytokines that were detected only in a minority of patients (Il-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-22, CCL3, and TNF-α) were left out from the bioinformatical analysis (Figure 4). The frequency of patients with capillary leak syndrome did not differ significantly between the two main clusters. The majority of patients later developed capillary leak syndrome clustered in the upper part, that is, 18 of the upper 24 patients (Figure 4). In contrast only six of the lower 32 patients developed capillary leak syndrome (Figure 4). This observation suggests that many patients with capillary leak syndrome show similarities in their pretransplant cytokine profile, but in contrast to the metabolite clustering (Figure 2) these similarities are not sufficient to cause statistically significant differences between main clusters. Thus, our hypothesis is that metabolic differences are more important than cytokine differences for the predisposition to capillary leak syndrome in allotransplant recipients.


Metabolic Serum Profiles for Patients Receiving Allogeneic Stem Cell Transplantation: The Pretransplant Profile Differs for Patients with and without Posttransplant Capillary Leak Syndrome.

Reikvam H, Grønningsæter IS, Ahmed AB, Hatfield K, Bruserud Ø - Dis. Markers (2015)

Hierarchical clustering based on the cytokine profiles: a study of the first 56 consecutive patients. Based on the pretransplant cytokine levels we performed an unsupervised hierarchal clustering analysis (Euclidean distance measure with WPGMA linkage). The figure presents the heat map with corresponding dendrograms. The horizontal cytokine clustering is seen at the top of the figure and the vertical patient clustering at the left part of the figure. Red color indicates high levels and green color low levels. The right column shows the distribution of patients with capillary leak syndrome, that is, weight increase ≥5 kg marked with red bars and the others marked with green.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4644835&req=5

fig4: Hierarchical clustering based on the cytokine profiles: a study of the first 56 consecutive patients. Based on the pretransplant cytokine levels we performed an unsupervised hierarchal clustering analysis (Euclidean distance measure with WPGMA linkage). The figure presents the heat map with corresponding dendrograms. The horizontal cytokine clustering is seen at the top of the figure and the vertical patient clustering at the left part of the figure. Red color indicates high levels and green color low levels. The right column shows the distribution of patients with capillary leak syndrome, that is, weight increase ≥5 kg marked with red bars and the others marked with green.
Mentions: Furthermore, we also performed unsupervised hierarchal clustering analyses based on the pretransplant cytokine levels. Cytokines that were detected only in a minority of patients (Il-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-22, CCL3, and TNF-α) were left out from the bioinformatical analysis (Figure 4). The frequency of patients with capillary leak syndrome did not differ significantly between the two main clusters. The majority of patients later developed capillary leak syndrome clustered in the upper part, that is, 18 of the upper 24 patients (Figure 4). In contrast only six of the lower 32 patients developed capillary leak syndrome (Figure 4). This observation suggests that many patients with capillary leak syndrome show similarities in their pretransplant cytokine profile, but in contrast to the metabolite clustering (Figure 2) these similarities are not sufficient to cause statistically significant differences between main clusters. Thus, our hypothesis is that metabolic differences are more important than cytokine differences for the predisposition to capillary leak syndrome in allotransplant recipients.

Bottom Line: Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications.Patients with later capillary leak syndrome showed increased pretherapy levels of metabolites associated with endothelial dysfunction (homocitrulline, adenosine) altered renal regulation of fluid and/or electrolyte balance (betaine, methoxytyramine, and taurine) and altered vascular function (cytidine, adenosine, and methoxytyramine).Our observations are consistent with the hypothesis that the pretransplant metabolic status can be a marker for posttransplant abnormal fluid and/or electrolyte balance.

View Article: PubMed Central - PubMed

Affiliation: Section Hematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Section Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.

ABSTRACT
Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications. Capillary leak syndrome is a common early posttransplant complication where endothelial cell dysfunction probably contributes to the pathogenesis. In the present study we investigated whether the pretreatment serum metabolic profile reflects a risk of posttransplant capillary leak syndrome. We investigated the pretransplant serum levels of 766 metabolites for 80 consecutive allotransplant recipients. Patients with later capillary leak syndrome showed increased pretherapy levels of metabolites associated with endothelial dysfunction (homocitrulline, adenosine) altered renal regulation of fluid and/or electrolyte balance (betaine, methoxytyramine, and taurine) and altered vascular function (cytidine, adenosine, and methoxytyramine). Additional bioinformatical analyses showed that capillary leak syndrome was also associated with altered purine/pyrimidine metabolism (i.e., metabolites involved in vascular regulation and endothelial functions), aminoglycosylation (possibly important for endothelial cell functions), and eicosanoid metabolism (also involved in vascular regulation). Our observations are consistent with the hypothesis that the pretransplant metabolic status can be a marker for posttransplant abnormal fluid and/or electrolyte balance.

No MeSH data available.


Related in: MedlinePlus