Evaluation of the demographic and clinical findings of pediatric patients that developed acute graft-versus-host disease after allogeneic hematopoietic stem cell

Aim: Acute graft-versus-host disease (GVHD) is an complication after allogeneic hematopoietic stem cell transplantation (alloHSCT), manifesting with an erythematous maculopapular rash followed by liver disease and dysfunctions of the gastrointestinal tract. This study aimed to retrospectively investigate the demographic and clinical characteristics of pediatric patients diagnosedwith acute GVHD after undergoing allo-HSCT due to various hematological diseases.Material and Methods: The study included 33 pediatric patients that underwent their first allogeneic bone marrow transplantation in the Pediatric Bone Marrow Transplant Unit between 2015 and 2018 and were consecutively diagnosed with acute GVHD in consultation with the department of dermatology. The demographic characteristics, clinical findings, donor characteristics,treatments, and survival status of each patient were recorded.Results: Between 2015 and 2018, bone marrow transplantation was performed in 150 pediatric patients, of whom 33 (22%) developed acute GVHD. Of the 33 pediatric patients, 19 (57.6%) were boys and 14 (42.4%) were girls. At the time of transplantation, the mean age of the patients was 8.5 years, and the median age was 7 years. Twenty patients (60.6%) had only skin GVHD while 13 (39.4%)had skin and gastrointestinal and/or hepatic GVHD. It was found that the rashes had appeared on average 27.4 days after allo-HSCT. Palmoplantar involvement was detected in 13 patients (39.4%), painful erosion in the oral mucosa in 11 (33%), and conjunctivitis in seven (21.2%). The factors of being a male patient, being a female donor, transplantation from unrelated donors, liver involvement,and palmoplantar involvement were found to create risk of mortality, but not significantly (respectively p=0,753;p=0,145,0,66). Five patients (15%) progressed from acute to chronic GVHD. In patients that progressed from acute to chronic had, the mean donor age was higher, the mean time from transplantation to rash was longer, and oral involvement was higher, but not significantly(respectively; p=0,596;p=0,980;p=0,193.Conclusion: In acute GVHD, the skin is the first and most involved organ; therefore, dermatologists play an important role in its diagnosis. This study is important for determining the factors affecting the decrease in progression to chronic GVHD and prolonging survival.

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1. Sung AD, Chao NJ. Acute graft-versus-host disease: Are we close to bringing the bench to the bedside? Best Pract Res Clin Haematol 2013;26:285-92.
2. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versushost disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005;11:945-56.
3. 3. MacMillan ML, Holtan SG, Rashidi A, et al. Pediatric acute GVHD: clinical phenotype and response to upfront steroids. Bone Marrow Transplant 2019;55:165-71.
4. Johnson MR, Farmer ER. Graft-versus-host reactions in dermatology. J Am Acad Dermatol 1998;38:369-92.
5. Couriel D, Caldera H, Champlin R, et al. Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management. Cancer 2004;101:1936-46.
6. Ramachandran V, Kolli SS, Strowd LC. Review of graftversus-host disease. Dermatol Clin 2019;37:569-82.
7. Przepiorka D, Weisdorf D, Martin P, et al. 1994 consensus conference on Acute GVHD grading. Bone Marrow Transplant 1995;15:825-8.
8. Faraci M, Giardino S, Bagnasco F, et al. Allogeneic hematopoietic stem cell transplantation in congenital disorders: A single-center experience. Pediatr Transplant 2017;21.
9. Goddard DS, Horn BN, McCalmont TH, et al. Clinical update on graft-versus-host disease in children. Semin Cutan Med Surg 2010;29:92-105.
10. Aladag E, Kelkitli E, Goker H. Acute graft versus host disease: A brief review. Turk J Haematol 2019.
11. Lee SE, Cho BS, Kim JH, et al. Risk and prognostic factors for acute GVHD based on NIH consensus criteria. Bone Marrow Transplant 2013;48:587-92.
12. Sanli H, Ekmekçi P, Arat M, et al. Clinical manifestations of cutaneous graft-versus-host disease after allogeneic haematopoietic cell transplantation: Longterm follow-up results in a single Turkish centre. Acta Derm Venereol 2004;84:296-301.
13. Ion D, Stevenson K, Woo SB, et al. Characterization of oral involvement in acute graft-versus-host disease. Biol Blood Marrow Transplant 2014;20:1717-21.
14. Saito T, Shinagawa K, Takenaka K, et al. Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation. Int J Hematol 2002;75:332-4.
15. Baird K, Cooke K, Schultz KR. Chronic graft versus host disease (GVHD) in children. Pediatr Clin North Am 2010;57:297-322.
16. Svennilson J, Remberger M, Ringdén O. Risk factors for moderate-to-severe acute graft-vs.-host disease after allogeneic stem cell transplantation in children. Pediatr Transplant 2003;7:130-6.
17. Harris AC, Ferrara JL, Levine JE. Advances in predicting acute GVHD. Br J Haematol 2013;160:288-302.
18. Hu SW, Cotliar J. Acute graft-versus-host disease following hematopoietic stem-cell transplantation. Dermatol Ther 2011;24:411-23.
19. Carreras E, Dufour C, Mohty M, et al. (2019), The EBMT handbook hematopoietic stem cell transplantation and cellular therapies. Switzerland: Springer