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Composite biomarker panel for prediction of severity and diagnosis of acute GVHD with T-cell-depleted allogeneic stem cell transplants—single centre pilot study
  1. San San Min1,
  2. Varun Mehra2,
  3. Jennifer Clay2,
  4. Gemma F Cross1,
  5. Abdel Douiri3,
  6. Tracy Dew1,
  7. Tanya N Basu4,
  8. Victoria Potter2,
  9. M Mansour Ceesay2,
  10. Antonio Pagliuca2,
  11. Roy A Sherwood1,
  12. Royce P Vincent1
  1. 1Department of Clinical Biochemistry (Viapath), King's College Hospital NHS Foundation Trust, London, UK
  2. 2Department of Haematology, King's College Hospital NHS Foundation Trust, London, UK
  3. 3Department of Primary Care and Public Health Sciences, King's College London, London, UK
  4. 4Department of Dermatology, King's College Hospital NHS Foundation Trust, London, UK
  1. Correspondence to Dr Varun Mehra, Department of Haematology, King's College Hospital NHS Foundation Trust, London SE5 9RS, UK; varun.mehra{at}nhs.net

Abstract

Aims Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical utility of a composite biomarker panel to help identify individuals at risk of developing aGVHD, and to help predict and differentiate between severity of aGVHD following T-cell-depleted allogeneic HSCT.

Methods We retrospectively analysed our cohort of biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and matched them with negative controls without any evidence of aGVHD. Post-transplant serum samples on days 0 and 7 and at onset of aGVHD were analysed for elafin, regenerating islet-derived 3-α, soluble tumour necrosis factor receptor-1, soluble interleukin-2 receptor-α and hepatocyte growth factor. Biomarker data were combined as composite panels A–F (table 2) using logistic regression analysis. Receiver operating characteristic analysis was performed to study sensitivity and specificity of the composite panels.

Results Our composite biomarker panels significantly differentiated between aGVHD and no GVHD patients at time of onset (panel E) and reliably predicted severity of GVHD grades at days 0 and 7 post-transplant (panels B and D). The area under the curve for the composite panel at time of onset was 0.65 with specificity, sensitivity, positive and negative predictive values of 100%, 55.6%, 100% and 78.9%, respectively (p=0.03).

Conclusions This pilot data support the usefulness of these composite biomarker panels in the prediction of severity and diagnosis of aGVHD in patients undergoing T-cell-depleted reduced intensity allogeneic HSCT.

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Footnotes

  • SSM and VM contributed equally to this work.

  • Handling editor Mary Frances McMullin

  • Contributors SSM: study design, collection of data, analyses of specimens and statistics including the panel, interpretation of data, drafting of the manuscript, critical review of the manuscript's content and approval of the final version submitted for publication; VM: study design, interpretation of data, drafting of the manuscript, critical review of the manuscript's content and approval of the final version submitted for publication; JC: study design, data collection, critical review of the manuscript's content and approval of the final version submitted for publication; GFC and TD: technical assistance on analyses of specimens, interpretation of data, critical review of the manuscript's content and approval of the final version submitted for publication; AD: statistic advice to develop biomarker panels, interpretation of data, critical review of the manuscript's content and approval of the final version submitted for publication; VP and AP: study design, interpretation of data, critical review of the manuscript's content and approval of the final version submitted for publication; MMC: study design, ethical approval for the previous antifungal study, collection of samples and data, interpretation of data, drafting of the manuscript, critical review of the manuscript's content and approval of the final version submitted for publication. RS, RPV and TNB: study design, interpretation of data, drafting of the manuscript, critical review of the manuscript's content and approval of the final version submitted for publication.

  • Funding SSM and RPV received funding from Viapath Pathology, UK (Innovation Fund). The rest of the project was funded by department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, London, UK. The assay method validation and analysis of patients’ samples was carried out by the first author as part of FRCPath project with technical assistance by state registered staff.

  • Competing interests None declared.

  • Ethics approval We have used the samples and clinical data on subjects recruited from the Kings Invasive Aspergillosis Anti-fungal study (REC no: 08/HA0808/154; R & D 08HA11; ClinicalTrials.gov No. NCT00816088). Guarantor: RPV.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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