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Open Access 18-04-2023 | Magnetic Resonance Imaging | Gastrointestinal

Multi-parametric MRI in the diagnosis and scoring of gastrointestinal acute graft-versus-host disease

Authors: Francesca Maccioni, Ursula La Rocca, Alberto Milanese, Ludovica Busato, Arianna Cleri, Mariangela Lopez, Lucia Manganaro, Carlo De Felice, Cira Di Gioia, Anna Rita Vestri, Carlo Catalano, Anna Paola Iori

Published in: European Radiology | Issue 9/2023

Abstract

Objectives

Acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis relies on clinical, endoscopic, and pathological investigations. Our purpose is to assess the value of magnetic resonance imaging (MRI) in the diagnosis, staging, and prediction of GI-aGVHD-related mortality.

Methods

Twenty-one hematological patients who underwent MRI for clinical suspicion of acute GI-GVHD were retrospectively selected. Three independent radiologists, blinded to the clinical findings, reanalyzed MRI images. The GI tract was evaluated from stomach to rectum by analyzing fifteen MRI signs suggestive of intestinal and peritoneal inflammation. All selected patients underwent colonoscopy with biopsies. Disease severity was determined on the basis of clinical criteria, identifying 4 stages of increasing severity. Disease-related mortality was also assessed.

Results

The diagnosis of GI-aGVHD was histologically confirmed with biopsy in 13 patients (61.9%). Using 6 major signs (diagnostic score), MRI showed 84.6% sensitivity and 100% specificity in identifying GI-aGVHD (AUC = 0.962; 95% confidence interval 0.891–1). The proximal, middle, and distal ileum were the segments most frequently affected by the disease (84.6%). Using all 15 signs of inflammation (severity score), MRI showed 100% sensitivity and 90% specificity for 1-month related mortality. No correlation with the clinical score was found.

Conclusion

MRI has proved to be an effective tool for diagnosing and scoring GI-aGVHD, with a high prognostic value. If larger studies will confirm these results, MRI could partly replace endoscopy, thus becoming the primary diagnostic tool for GI-aGVHD, being more complete, less invasive, and more easily repeatable.

Key Points

• We have developed a new promising MRI diagnostic score for GI-aGVHD with a sensitivity of 84.6% and specificity of 100%; results are to be confirmed by larger multicentric studies.

• This MRI diagnostic score is based on the six MRI signs most frequently associated with GI-aGVHD: small-bowel inflammatory involvement, bowel wall stratification on T2-w images, wall stratification on post-contrast T1-w images, ascites, and edema of retroperitoneal fat and declivous soft tissues.

• A broader MRI severity score based on 15 MRI signs showed no correlation with clinical staging but high prognostic value (100% sensitivity, 90% specificity for 1-month related mortality); these results also need to be confirmed by larger studies.

Passweg JR, Baldomero H, Bader P et al (2016) Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant 51:786–792. https://doi.org/10.1038/bmt.2016.20CrossRefPubMedPubMedCentral

Baron F, Storb R (2004) Allogeneic hematopoietic cell transplantation as treatment for hematological malignancies: a review. Springer Semin Immunopathol 26:71–94. https://doi.org/10.1007/s00281-004-0165-3CrossRefPubMed

Servais S, Beguin Y, Delens L et al (2016) Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Expert Opin Investig Drugs 25:957–972. https://doi.org/10.1080/13543784.2016.1182498CrossRefPubMed

del Campo L, León NG, Palacios DC, Lagana C, Tagarro D (2014) Abdominal complications following hematopoietic stem cell transplantation. Radiographics 34:396–412. https://doi.org/10.1148/rg.342135046CrossRefPubMed

Zeiser R, Blazar BR (2017) Acute graft-versus-host disease - biologic process, prevention, and therapy. N Engl J Med 377(22):2167–2179. https://doi.org/10.1056/NEJMra1609337CrossRefPubMedPubMedCentral

Jacobsohn DA, Vogelsang GB (2007) Acute graft versus host disease. Orphanet J Rare Dis 2:35CrossRefPubMedPubMedCentral

Ferrara JLM, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373:1550–1561. https://doi.org/10.1016/S0140-6736(09)60237-3CrossRefPubMedPubMedCentral

Filipovich AH, Weisdorf D, Pavletic S et al (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 11:945–956. https://doi.org/10.1016/j.bbmt.2005.09.004CrossRefPubMed

Malard F, Huang X, Sim JPY (2020) Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia 34:1229–1240. https://doi.org/10.1038/s41375-020-0804-2CrossRefPubMedPubMedCentral

10.

Al-Kadhimi Z, Gul Z, Chen W et al (2014) (2014) High incidence of severe acute graft-versus-host disease with tacrolimus and mycophenolate mofetil in a large cohort of related and unrelated allogeneic transplantation patients. Biol Blood Marrow Transpl 20:979–985CrossRef

11.

Jagasia MH, Greinix HT, Arora M et al (2015) National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant 21(3):389–401.e1. https://doi.org/10.1016/j.bbmt.2014.12.001

12.

Martin PJ, Schoch G, Fisher L et al (1990) A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 76:1464–1472CrossRefPubMed

13.

Vogelsang GB, Lee L, Bensen-Kennedy DM (2003) Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant. Annu Rev Med 54:29–52. https://doi.org/10.1146/annurev.med.54.101601.152339CrossRefPubMed

14.

Lubner MG, Menias CO, Agrons M et al (2017) Imaging of abdominal and pelvic manifestations of graft-versus-host disease after hematopoietic stem cell transplant. AJR Am J Roentgenol 209:33–45. https://doi.org/10.2214/AJR.17.17CrossRefPubMed

15.

Fallows G, Rubinger M, Bernstein CN (2001) Does gastroenterology consultation change management of patients receiving hematopoietic stem cell transplantation? Bone Marrow Transplant 28:289–294. https://doi.org/10.1038/sj.bmt.1703130CrossRefPubMed

16.

Glucksberg H, Storb R, Fefer A et al (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18(4):295–304

17.

Kalantari BN, Mortelé KJ, Cantisani V et al (2003) CT features with pathologic correlation of acute gastrointestinal graft-versus-host disease after bone marrow transplantation in adults. AJR Am J Roentgenol 181:1621–1625. https://doi.org/10.2214/ajr.181.6.1811621CrossRefPubMed

18.

Mahgerefteh SY, Sosna J, Bogot N, Shapira MY, Pappo O, Bloom AI (2011) Radiologic imaging and intervention for gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. Radiology 258:660–671. https://doi.org/10.1148/radiol.10100025

19.

Brodoefel H, Bethge W, Vogel M et al (2010) Early and late-onset acute GvHD following hematopoietic cell transplantation: CT features of gastrointestinal involvement with clinical and pathological correlation. Eur J Radiol 73:594–600. https://doi.org/10.1016/j.ejrad.2009.01.011CrossRefPubMed

20.

Shimoni A, Rimon U, Hertz M et al (2012) CT in the clinical and prognostic evaluation of acute graft-vs-host disease of the gastrointestinal tract. Br J Radiol 85:e416-423. https://doi.org/10.1259/bjr/60038597CrossRefPubMedPubMedCentral

21.

Schmit M, Bethge W, Beck R et al (2008) CT of gastrointestinal complications associated with hematopoietic stem cell transplantation. AJR Am J Roentgenol 190:712–719. https://doi.org/10.2214/AJR.07.2628CrossRefPubMed

22.

Rashidi A, Lin MF, Cashen AF (2016) Early post-transplant contrast-enhanced abdominopelvic CT scan predicts the risk of subsequent acute GvHD. Bone Marrow Transplant 51:150–152. https://doi.org/10.1038/bmt.2015.232CrossRefPubMed

23.

Klein SA, Martin H, Schreiber-Dietrich D et al (2001) A new approach to evaluating intestinal acute graft-versus-host disease by transabdominal sonography and colour Doppler imaging. Br J Haematol 115:929–934. https://doi.org/10.1046/j.1365-2141.2001.03221.x

24.

Görg C, Wollenberg B, Beyer J, Stolte MS, Neubauer A (2005) High-resolution ultrasonography in gastrointestinal graft-versus-host disease. Ann Hematol 84:33–39. https://doi.org/10.1007/s00277-004-0893-4

25.

Roll W, Evers G, Strotmann R et al (2021) F-FDG-PET for the assessment of acute intestinal GvHD and prediction of response to immunosuppressive therapy. Transplant Cell Ther. https://doi.org/10.1016/j.jtct.2021.04.011

26.

Worawattanakul S, Semelka RC, Kelekis NL, Sallah AS (1996) MR findings of intestinal graft-versus-host disease. Magn Reson Imaging 14:1221–1223. https://doi.org/10.1016/s0730-725x(96)00245-7CrossRefPubMed

27.

Budjan J, Michaely HJ, Attenberger U et al (2014) Assessment of acute intestinal graft versus host disease by abdominal magnetic resonance imaging at 3 tesla. Eur Radiol 24:1835–1844. https://doi.org/10.1007/s00330-014-3224-8CrossRefPubMed

28.

Derlin T, Laqmani A, Veldhoen S et al (2015) Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation. Eur Radiol 25:1229–1237. https://doi.org/10.1007/s00330-014-3503-4CrossRefPubMed

29.

Maccioni F, Bruni A, Viscido A et al (2006) MR imaging in patients with Crohn disease: value of T2- versus T1-weighted gadolinium-enhanced MR sequences with use of an oral superparamagnetic contrast agent. Radiology 238:517–530. https://doi.org/10.1148/radiol.2381040244

30.

Horsthuis K, Bipat S, Stokkers PCF, Stoker J (2009) Magnetic resonance imaging for evaluation of disease activity in Crohn’s disease: a systematic review. Eur Radiol 19:1450–1460. https://doi.org/10.1007/s00330-008-1287-0

31.

Amzallag-Bellenger E, Oudjit A, Ruiz A, Cardiot G, Soyer PA, Hoeffel CC (2012) Effectiveness of MR enterography for the assessment of small-bowel diseases beyond Crohn disease. Radiographics 32:1423–1444. https://doi.org/10.1148/rg.325115088

32.

Maccioni F, Patak MA, Signore A, Laghi A (2012) New frontiers of MRI in Crohn’s disease: motility imaging, diffusion-weighted imaging, perfusion MRI, MR spectroscopy, molecular imaging, and hybrid imaging (PET/MRI). Abdom Imaging 37(6):974–982. https://doi.org/10.1007/s00261-012-9890-6CrossRefPubMed

33.

Rimola J, Rodriguez S, García-Bosch O et al (2009) Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease. Gut 58(8):1113–1120. https://doi.org/10.1136/gut.2008.167957CrossRefPubMed

34.

Ippolito D, Invernizzi F, Galimberti S, Panelli M R, Sironi S (2010) MR enterography with polyethylene glycol as oral contrast medium in the follow-up of patients with Crohn disease: comparison with CT enterography. Abdom Imaging. 35(5):563-70. https://doi.org/10.1007/s00261-009-9557-0

35.

Nalle SC, Turner JR (2015) Intestinal barrier loss as a critical pathogenic link between inflammatory bowel disease and graft-versus-host disease. Mucosal Immunol. https://doi.org/10.1038/mi.2015.40CrossRefPubMed

36.

Yamada S, Takatsuka H, Takemoto Y et al (2001) Acute colonic graft-versus-host disease and ulcerative colitis with respect to cytokines. Hematology. https://doi.org/10.1080/10245332.2001.11746585CrossRefPubMed

37.

Penack O, Marchetti M, Ruutu T et al (2020) Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 7:157–167CrossRef

38.

Lee SJ, Zahrieh D, Agura E et al (2004) Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood. https://doi.org/10.1182/blood-2004-03-0854CrossRefPubMed

39.

Bacigalupo A, Angelucci E, Raiola AM et al (2020) Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody—Begelomab. Bone Marrow Transplant 55:1580–1587CrossRefPubMed

40.

Couriel D, Caldera H, Champlin R, Komanduri K (2004) Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management. Cancer 101:1936–1946. https://doi.org/10.1002/cncr.20613CrossRefPubMed

41.

Rimola J, Torres J, Kumar S, Taylor SA, Kucharzik T (2022) Recent advances in clinical practice: advances in cross-sectional imaging in inflammatory bowel disease. Gut 71(12):2587–2597. https://doi.org/10.1136/gutjnl-2021-326562CrossRefPubMed

Title: Multi-parametric MRI in the diagnosis and scoring of gastrointestinal acute graft-versus-host disease
Authors: Francesca Maccioni
Ursula La Rocca
Alberto Milanese
Ludovica Busato
Arianna Cleri
Mariangela Lopez
Lucia Manganaro
Carlo De Felice
Cira Di Gioia
Anna Rita Vestri
Carlo Catalano
Anna Paola Iori
Publication date: 18-04-2023
Publisher: Springer Berlin Heidelberg
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Edema
Graft-Versus-Host Disease
Graft-Versus-Host Disease
Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Published in: European Radiology / Issue 9/2023
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-023-09563-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Multi-parametric MRI in the diagnosis and scoring of gastrointestinal acute graft-versus-host disease

Abstract

Objectives

Methods

Results

Conclusion

Key Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusion

Key Points

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