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. 2013 Aug 22;122(8):1505-9.
doi: 10.1182/blood-2013-02-485813. Epub 2013 Jun 12.

Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality

John E Levine  1 , Elisabeth Huber, Suntrea T G Hammer, Andrew C Harris, Joel K Greenson, Thomas M Braun, James L M Ferrara, Ernst Holler
Affiliations

Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality

John E Levine et al. Blood. .

Abstract

Acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is an often lethal complication of allogeneic hematopoietic cell transplant. Clinical severity correlates with outcomes, but histopathologic grading is primarily used to confirm the clinical diagnosis. One barrier to using histopathologic grading to predict clinical outcomes is inter-grader variability among transplant centers. Recent experimental models have shown that the loss of Paneth cells, which are located in the small intestine and help regulate the GI microbiome by secreting antimicrobial peptides, correlates with clinical GVHD severity. Because Paneth cells are easy to identify and quantify by light microscopy, we evaluated the mean number of Paneth cells per high-powered field (hpf) in 116 duodenal biopsies obtained at diagnosis of GI GVHD at 2 different centers with their clinical outcomes. Paneth cell counts were reproducible between centers (r(2) = 0.81; P < .0001). Lower numbers of Paneth cells at diagnosis correlated with clinically more severe GI GVHD (P < .0001) and less likelihood of response to GVHD treatment (P < .0001). A threshold of 4 Paneth cells per hpf stratified patients according to nonrelapse mortality (28% vs 56%; P = .004). We conclude that the enumeration of duodenal Paneth cells is a readily available index of disease severity that provides important information regarding GVHD prognosis.

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Figures

Figure 1
Figure 1
Paneth cell count correlates with GI GVHD clinical severity at onset. Mean Paneth cell counts per hpf (horizontal lines show mean of the means) were significantly different (P < .0001) in biopsies obtained at the onset of GI GVHD stage 1 (n = 69), 2 (n = 18), 3 (n = 12), and 4 (n = 16).
Figure 2
Figure 2
Paneth cell count at onset correlates with GI GVHD response to treatment. Mean Paneth cell counts per hpf (horizontal lines show median of the means) were significantly different (P < .0001) in biopsies obtained from control patients without GI GVHD (n = 26) and at the onset of GI GVHD in patients whose 4-week response to treatment was complete response (CR, n = 56), partial response (PR, n = 24), or no response/progression (NR, n = 34). The interquartile range of mean Paneth cell counts per hpf was 5.7 to 16.9 for CR, 1 to 12.5 for PR, and 0 to 6.1 for NR.
Figure 3
Figure 3
Cumulative incidence of NRM after GVHD onset, stratified by Paneth cell count. Patients with a mean Paneth cell count per hpf ≥4 (n = 75, solid line) at the time of GI GVHD onset experienced significantly less NRM than the 42 patients (dashed line) with a mean Paneth cell count per hpf <4 (28% vs 56%; P = .004).
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References

    1. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373(9674):1550–1561. - PMC - PubMed
    1. Ferrara JL, Harris AC, Greenson JK, et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood. 2011;118(25):6702–6708. - PMC - PubMed
    1. MacMillan ML, DeFor TE, Weisdorf DJ. What predicts high risk acute graft-versus-host disease (GVHD) at onset?: identification of those at highest risk by a novel acute GVHD risk score. Br J Haematol. 2012;157(6):732–741. - PMC - PubMed
    1. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on acute GVHD grading. Bone Marrow Transplant. 1995; 15(6):825-828. - PubMed
    1. Rowlings PA, Przepiorka D, Klein JP, et al. IBMTR severity index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997;97(4):855–864. - PubMed

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