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Allogeneic donor split skin grafts for treatment of refractory ulcers in cutaneous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation—a retrospective analysis on seven patients

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Abstract

Refractory skin ulcers due to severe chronic graft-versus-host disease (cGVHD) remain to be associated with significant morbidity and mortality.

We performed an allogeneic donor skin transplantation in seven adult patients after allogeneic hematopoietic stem cell transplantation for cGVHD-associated refractory skin ulcers. While four patients received a split skin graft (SSG), in one patient, a full thickness skin graft for two small refractory ulcers of the ankle was performed, and one patient received in vitro expanded donor keratinocyte grafts derived from hair roots of the original unrelated donor. In one additional patient, a large deep fascial defect of the lower leg was covered with an autologous greater omentum free graft before coverage with an allogeneic SSG. An additional patient was treated with an autologous scrotal skin graft for a refractory ulcer associated with deep sclerosis of cGVHD after unrelated donor transplantation.

All skin grafts engrafted and resulted in permanent coverage of the grafted ulcers without any signs of immunological mediated damage. In the patient receiving in vitro expanded keratinocyte grafts, two localized ulcers were permanently covered by donor skin while this approach failed to cover extensive circular ulcers of the lower legs.

Allogeneic donor skin grafts are a valuable treatment option in refractory ulcers due to cGVHD but are restricted mainly to related donors while keratinocyte grafts from unrelated donors remain experimental. In male patients lacking a related donor, autologous scrotal skin graft may be an alternative option.

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References

  1. Ferrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373:1550–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Arai S, Arora M, Wang T, Spellman SR, He W, Couriel DR, Urbano-Ispizua A, Cutler CS, Bacigalupo AA, Battiwalla M, Flowers ME, Juckett MB, Lee SJ, Loren AW, Klumpp TR, Prockup SE, Ringdén OT, Savani BN, Socié G, Schultz KR, Spitzer T, Teshima T, Bredeson CN, Jacobsohn DA, Hayashi RJ, Drobyski WR, Frangoul HA, Akpek G, Ho VT, Lewis VA, Gale RP, Koreth J, Chao NJ, Aljurf MD, Cooper BW, Laughlin MJ, Hsu JW, Hematti P, Verdonck LF, Solh MM, Norkin M, Reddy V, Martino R, Gadalla S, Goldberg JD, McCarthy P, Pérez-Simón JA, Khera N, Lewis ID, Atsuta Y, Olsson RF, Saber W, Waller EK, Blaise D, Pidala JA, Martin PJ, Satwani P, Bornhäuser M, Inamoto Y, Weisdorf DJ, Horowitz MM, Pavletic SZ, Graft-vs-Host Disease Working Committee of the CIBMTR (2015) Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant 21:266–274

    Article  PubMed  Google Scholar 

  3. Grube M, Holler E, Weber D, Holler B, Herr W, Wolff D (2016) Risk factors and outcome of chronic graft-versus-host disease after allogeneic stem cell transplantation-results from a single-center observational study. Biol Blood Marrow Transplant 22:1781–1791

    Article  PubMed  Google Scholar 

  4. Marks C, Stadler M, Hausermann P et al (2011) German-Austrian-Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease (GVHD): guidance for supportive therapy of chronic cutaneous and musculoskeletal GVHD. Br J Dermatol 165:18–29

    Article  CAS  PubMed  Google Scholar 

  5. Inamoto Y, Storer BE, Petersdorf EW, Nelson JL, Lee SJ, Carpenter PA, Sandmaier BM, Hansen JA, Martin PJ, Flowers MED (2013) Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood 121:5098–5103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rizzo JD, Curtis RE, Socie G et al (2009) Solid cancers after allogeneic hematopoietic cell transplantation. Blood 113:1175–1183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Curtis RE, Metayer C, Rizzo JD, Socié G, Sobocinski KA, Flowers ME, Travis WD, Travis LB, Horowitz MM, Deeg HJ (2005) Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 105:3802–3811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Amendola F, Gazzola R, Lombardo M, Caminiti R, Dagna L, Baruffaldi-Preis FW (2016) Chronic ulcer by cutaneous GvHD after bone marrow transplantation treated with skin allograft from HLA-identical donor: case report and literature review. Int J Low Extrem Wounds 15:139–141

    Article  PubMed  Google Scholar 

  9. Ammer J, Prantl L, Holler B, Landfried K, Wolff D, Karrer S, Andreesen R, Holler E (2012) Successful treatment of a refractory skin ulcer in chronic cutaneous GvHD after allogeneic HSCT with split-thickness skin allografting from the stem cell donor. Bone Marrow Transplant 47:1368–1369

    Article  CAS  PubMed  Google Scholar 

  10. Baumeister RG, Riel KA, Kolb HJ (1990) Allogeneic skin transplantation in chronic graft-versus-host disease following bone marrow transplantation. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen 61:438–440

    CAS  PubMed  Google Scholar 

  11. Crocchiolo R, Nicolini FE, Sobh M, Ducastelle-Lepretre S, Labussiere H, Dubois V, Auxenfans C, Mojallal A, Damour O, Braye F, Michallet M (2011) Treatment of a severe extensive cutaneous chronic GVHD after allo-HSCT using glycerolyzed skin allografts and cultured epidermis from the same donor. Bone Marrow Transplant 46:1153–1155

    Article  CAS  PubMed  Google Scholar 

  12. Knobler HY, Sagher U, Peled IJ et al (1985) Tolerance to donor-type skin in the recipient of a bone marrow allograft. Treatment of skin ulcers in chronic graft-versus-host disease with skin grafts from the bone marrow donor. Transplantation 40:223–225

    Article  CAS  PubMed  Google Scholar 

  13. Kondo S, Tamura K, Makino S, Takamatsu Y (1994) Allogeneic skin grafting for extensive skin chronic graft-versus-host disease. Int J Hematol 60:151–155

    CAS  PubMed  Google Scholar 

  14. Tausche AK, Skaria M, Bohlen L, Liebold K, Hafner J, Friedlein H, Meurer M, Goedkoop RJ, Wollina U, Salomon D, Hunziker T (2003) An autologous epidermal equivalent tissue-engineered from follicular outer root sheath keratinocytes is as effective as split-thickness skin autograft in recalcitrant vascular leg ulcers. Wound Repair Regen 11:248–252

    Article  PubMed  Google Scholar 

  15. Cooke KR, Luznik L, Sarantopoulos S, Hakim FT, Jagasia M, Fowler DH, van den Brink MRM, Hansen JA, Parkman R, Miklos DB, Martin PJ, Paczesny S, Vogelsang G, Pavletic S, Ritz J, Schultz KR, Blazar BR (2017) The biology of chronic graft-versus-host disease: a task force report from the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. Biol Blood Marrow Transplant 23:211–234

    Article  PubMed  Google Scholar 

  16. Biedermann BC (2008) Vascular endothelium and graft-versus-host disease. Best Pract Res Clin Haematol 21:129–138

    Article  CAS  PubMed  Google Scholar 

  17. Croudace JE, Inman CF, Abbotts BE, Nagra S, Nunnick J, Mahendra P, Craddock C, Malladi R, Moss PAH (2012) Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD. Blood 120:4246–4255

    Article  CAS  PubMed  Google Scholar 

  18. Martires KJ, Baird K, Citrin DE, Hakim FT, Pavletic SZ, Cowen EW (2011) Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury: potential insight into the mechanism of isomorphic and isotopic responses. Arch Dermatol 147:1081–1086

    Article  PubMed  Google Scholar 

  19. Brent L, Medawar PB (1963) Tissue transplantation: a new approach to the “typing” problem. Br Med J 2:269–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Berg JO, Vindelov L, Schmidt G, Drzewiecki KT (2008) Allogeneic split-skin grafting in stem cell transplanted patients. J Plastic Reconstr Aesthet Surg 61:1512–1515

    Article  CAS  Google Scholar 

  21. Saltz R (1995) Endoscopic harvest of the omental and jejunal free flaps. Clin Plast Surg 22:747–754

    CAS  PubMed  Google Scholar 

  22. Maloney CT Jr, Wages D, Upton J, Lee WP (2003) Free omental tissue transfer for extremity coverage and revascularization. Plast Reconstr Surg 111:1899–1904

    Article  PubMed  Google Scholar 

  23. MacNeil S (2008) Biomaterials for tissue engineering of skin. materialstoday 11:26–35

    CAS  Google Scholar 

  24. Zeiser R, Blazar BR (2017) Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med 377:2565–2579

    Article  CAS  PubMed  Google Scholar 

  25. Falanga V, Sabolinski M (1999) A bilayered living skin construct (APLIGRAF) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen 7:201–207

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the DKMS for organizing the hair donation of donor of patient 533/7.

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Correspondence to D. Wolff.

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DW and EH received honoraria from Novartis and Mallinckrodt. None of the others authors indicated a conflict of interest.

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ESM 1

Hyperproliferation of the split skin graft in patient 212 / 5 in the absence of inflammation (DOCX 985 kb)

ESM 2

a-c: a) Hair pulling for hair root harvest. b) Outer root sheath of hair follicle (arrow) consisting of progenitor cells. c) Keratinocyte transplants 5 days after surgery (DOCX 1994 kb)

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Lamby, P., Wolff, D., Mielke, S. et al. Allogeneic donor split skin grafts for treatment of refractory ulcers in cutaneous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation—a retrospective analysis on seven patients. Ann Hematol 98, 1867–1875 (2019). https://doi.org/10.1007/s00277-019-03687-x

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  • DOI: https://doi.org/10.1007/s00277-019-03687-x

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