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Blood, 15 July 2004, Vol. 104, No. 2, pp. 340-349.
Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2004-02-0518.


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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation

Thorsten Kaiser, Haytham Kamal, Andreas Rank, Hans-Jochem Kolb, Ernst Holler, Arnold Ganser, Bernd Hertenstein, Harald Mischak, and Eva Maria Weissinger

From Mosaiques Diagnostics & Therapeutics and Hannover Medical School, Departments of Hematology/Oncology and Nephrology, Hannover, Germany; Jose-Carreras-Unit, Klinikum Großhadern, München, Germany; and the Department of Hematology, University of Regensburg, Regensburg, Germany.

A phase 1 diagnostic study was performed to evaluate a novel technology for clinical proteom research based on capillary electrophoresis and mass spectrometry. Urine from 40 patients after hematopoietic stem cell transplantation (HSCT; 35 allogeneic, 5 autologous) and 5 patients with sepsis was collected for a period of 100 days and analyzed. More than 1000 different polypeptides could be detected in individual samples. Polypeptide patterns excreted in the urine of patients were significantly different from those of healthy volunteers. No significant differences were detected comparing different conditioning regimens. The aim of this study was to identify polypeptide patterns functioning as early indicators of graft-versus-host disease (GVHD). Eighteen patients developed GVHD after allogeneic HSCT. Sixteen differentially excreted polypeptides formed a pattern of early GVHD markers, allowing discrimination of GVHD from patients without complications with 82% specificity and 100% sensitivity, cross-validated. Inclusion of 13 sepsis-specific polypeptides allowed us to distinguish sepsis from GVHD with a specificity of 97% and a sensitivity of 100%. Sequencing 2 prominent GVHD-indicative polypeptides led to the identification of a peptide from leukotriene A4 hydrolase and a peptide from serum albumin. The data reveal that capillary electrophoresis and mass spectrometry allow identification of biomarkers for a variety of diseases or related complications. (Blood. 2004;104:340-349)


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