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Clinical versus histological grading in the assessment of cutaneous graft versus host disease.

ABSTRACT: BACKGROUND:Skin biopsies are often used in daily practice for the diagnosis of acute (aGvHD) or chronic graft versus host disease (cGvHD). With the latest understanding in pathogenesis and new National Institute of Health (NIH) classifications for aGvHD and cGvHD, there is a need to evaluate the current prognostic value of histological grading cutaneous GvHD and its correlation to the clinical grade. METHODS:In a retrospective study with 120 skin biopsies (all taken for suspected GvHD) from 110 patients (all classified according to the NIH), biopsies were revised and graded, blinded for clinical information, for either acute of chronic features. Morphological grades were compared for concordance with the clinical grade and survival analyses were done for clinical and histological grading. RESULTS:Correlation for histologic vs. clinical grading was (very) poor for aGvHD and cGvHD (weighted ? -?0.038 and 0.0009, respectively). Patients with clinical aGvHD had worse prognosis compared to cGvHD. However, at time of biopsy neither clinical nor histological grading predicted the eventual survival for either aGvHD (p?=?0.9739 and p?=?0.0744, respectively) or cGvHD (p?=?0.2149 and p?=?0.4465, respectively). CONCLUSIONS:Confirming the diagnosis of GvHD is still a valuable reason for taking a skin biopsy, but this study shows that histologic grading of GvHD in the skin biopsy has no additional value for clinicians in current practice.

SUBMITTER: Hogenes MCH

PROVIDER: S-EPMC6457000 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Clinical versus histological grading in the assessment of cutaneous graft versus host disease.

Hogenes M C H MCH Te Boome L C J LCJ van der Valk D C DC van Dijk M R MR de Weger R A RA Kuball J J van Diest P J PJ

European journal of medical research 20190410 1

<h4>Background</h4>Skin biopsies are often used in daily practice for the diagnosis of acute (aGvHD) or chronic graft versus host disease (cGvHD). With the latest understanding in pathogenesis and new National Institute of Health (NIH) classifications for aGvHD and cGvHD, there is a need to evaluate the current prognostic value of histological grading cutaneous GvHD and its correlation to the clinical grade.<h4>Methods</h4>In a retrospective study with 120 skin biopsies (all taken for suspected ...[more]

PMID: 30971293

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Project description:Allogeneic hematopoietic stem cell transplantation is a curative treatment for numerous hematological malignancies. However, acute graft-versus-host disease (aGvHD) is a major complication affecting 40-70% of all transplant patients, whereby the earliest and most frequent presentation is in the skin. MicroRNAs play a role in varied biological process and have been reported as potential biomarkers for aGvHD. More recently, microRNAs have received added attention as circulatory biomarkers that can be detected in biofluids. In this study, we performed global microRNA expression profiling using a discovery cohort of diagnostic cutaneous aGvHD biopsies (n = 5, stages 1-3) and healthy volunteers (n = 4), in order to identify a signature list of microRNAs that could be used as diagnostic biomarkers for cutaneous aGvHD. Candidate microRNAs (n = 8) were then further investigated in a validation cohort of post-HSCT skin biopsies (n = 17), pre-HSCT skin biopsies (n = 6) and normal controls (n = 6) for their association with aGvHD. Expression of let-7c (p = 0.014), miR-503-5p (p = 0.003), miR-365a-3p (p = 0.02), miR-34a-5p (p < 0.001) and miR-34a-3p (p = 0.006) were significantly differentially expressed between groups and significantly associated with survival outcome in post-HSCT patients (miR-503-5p ROC AUC = 0.83 p = 0.021, Log Rank p = 0.003; miR-34a-3p ROC AUC = 0.93, p = 0.003, Log Rank p = 0.004). There was no association with relapse. A statistical interaction between miR-34a-3p and miR-503-5p (p = 0.016) was diagnostic for aGvHD. Expression levels of the miR-34a-5p protein target p53 were assessed in the epidermis of the skin, and an inverse correlation was identified (r2 = 0.44, p = 0.039). Expression of the validated candidate microRNAs was also assessed at day 28 post-HSCT in the sera of transplant recipients, in order to investigate their potential as circulatory microRNA biomarkers. Expression of miR-503-5p (p = 0.001), miR-34a-5p (p = 0.005), and miR-34a-3p (p = 0.004) was significantly elevated in the sera of patients who developed aGvHD versus no-aGvHD (n = 30) and miR-503-5p was associated with overall survival (OS) (ROC AUC = 0.80, p = 0.04, Log Rank p = 0.041). In conclusion, this investigation reports that microRNA expression levels in clinical skin biopsies, obtained at the time of cutaneous aGvHD onset, show potential as diagnostic biomarkers for aGvHD and as predictive biomarkers for OS. In addition, the same microRNAs can be detected in the circulation and show predictive association with post-HSCT outcomes.

Project description:The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-host disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We developed a histologic activity grading system designed to replace the commonly used modified Lerner grading systems. Our system stratifies the low-level Lerner grade I category into 4 activity grade categories, based on the average frequency of apoptotic cells. The results are expressed as ordinal categories: GVHD of minimal, mild, moderate, severe histologic activity, or severe histologic activity with destruction (activity grades 1 to 5). In a retrospective study, we studied 87 consecutive cases with 201 post-transplantation specimens (median, 48 days; range, 18 to 1479 days) of stomach, duodenum, and colorectum, which had been activity graded at the time of the original diagnosis. Most of the biopsies diagnosed as GVHD were low grade-minimal (11%) or mild (71%) histologic activity. We hypothesized that the higher activity grades would be associated with more therapeutic intervention. The odds of increased therapy in the combined all-site specimens were increased as activity grade increased (odds ratio,?2.9 [95% confidence interval {CI}, 1.9 to 4.5]; P?=?<?.0001). Thus, our grading system was validated. To investigate whether the activity grade was associated with therapy within the formerly undivided Lerner grade I category, the analysis was restricted to these 174 all-site specimens. The validation result was similar (odds ratio,?3.1 [95% CI, 1.3 to 7.2]; P?=?.009). This result interestingly suggests that there is useful information hidden in the Lerner grade I category, which could potentially guide immediately actionable treatment decisions. This histologic activity grade system has been in use at our institution for over 2 years with good acceptance.

Dataset Information

Clinical versus histological grading in the assessment of cutaneous graft versus host disease.

Publications

Clinical versus histological grading in the assessment of cutaneous graft versus host disease.

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