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Cellular Therapy

A multicentre UK study of GVHD following DLI: Rates of GVHD are high but mortality from GVHD is infrequent

Bone Marrow Transplantation volume 50, pages 62–67 (2015)Cite this article

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Abstract

DLIs are frequently used following haematopoietic SCT (HSCT) in patients with risk of relapse but data on GVHD following DLI are scarce. We report on 68 patients who received DLI following HSCT. Most patients developed GVHD following DLI (71%), which was acute in 22 patients (32%) almost half of whom had grade III–IV acute GVHD (aGVHD). Thirty patients (44%) developed cGVHD which followed aGVHD in four patients and was graded severe in nine patients. Corticosteroids were the most common first-line therapy for both acute and chronic GVHD. A wide range of second/third-line agents included cyclosporin, mycophenolate, tacrolimus, imatinib, infliximab and ECP. Relapse of initial malignancy occurred in 37%. Relapse was significantly less frequent in those receiving pre-emptive DLI. Relapse rates were also lower in those with GVHD (31%) than those without GVHD (50%), but this did not reach statistical significance. At 55 months post DLI, 34% of patients had died most commonly from relapse and 22% had on-going GVHD. Although GVHD was an important cause of morbidity post DLI (71%), only 6% died from GVHD. Although most patients develop GVHD post DLI and may require consecutive therapies, mortality from GVHD is infrequent. DLI remains an important option for relapse post transplant and manipulation of the GVT effect needs to be optimised to induce remission without morbidity from GVHD.

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References

  1. Kolb HJ, Mittermüller J, Clemm C, Holler E, Ledderose G, Brehm G et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990; 76: 2462–2465.

    CAS  PubMed  Google Scholar 

  2. Kolb H, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  3. Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF . Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997; 90: 4206–4211.

    CAS  PubMed  Google Scholar 

  4. Porter D, Roth M, McGarigle C, Ferrara J, Antin J . Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med 1994; 330: 100–106.

    CAS  PubMed  Google Scholar 

  5. Mackinnon S, Papadopoulos E, Carabasi M, Reich L, Collins NH, Boulad F et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 1995; 86: 1261–1268.

    CAS  PubMed  Google Scholar 

  6. Jr1 Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  7. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  8. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  9. Martin PJ, Weisdorf D, Przepiorka D, Hirschfeld S, Farrell A, Rizzo JD et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report. Biol Blood Marrow Transplant 2006; 12: 491–505.

    Article  PubMed  Google Scholar 

  10. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National institutes of health consensus development project on criteria for clinical trials in chronic graftversus-host disease. I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  11. Greinix HT, Volc-Platzer B, Rabitsch W, Gmeinhart B, Guevara-Pineda C, Kalhs P et al. Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease. Blood 1998; 92: 3098–3104.

    CAS  PubMed  Google Scholar 

  12. Li JM, Giver CR, Lu Y, Hossain MS, Akhtari M, Waller EK . Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Immunotherapy 2009; 1: 599–621.

    CAS  PubMed  Google Scholar 

  13. Meyer RG, Britten CM, Wehler D, Bender K, Hess G, Konur A et al. Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation. Blood 2007; 109: 374–382.

    Article  CAS  PubMed  Google Scholar 

  14. Burt RK, Drobyski WR, Traynor AE, Link CJ Jr . Herpes simplex thymidine kinase (HStk) transgenic donor lymphocytes. Bone Marrow Transplant 1999; 24: 1043–1051.

    Article  CAS  PubMed  Google Scholar 

  15. Deol A, Lum L . Role of donor lymphocyte infusions in relapsed haematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 2010; 36: 528–538.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hofmann S, Greiner J . Adoptive immunotherapy after allogeneic hematopoietic progenitor cell transplantation: new perspectives for transfusion medicine. Transfus Med Hemother 2011; 38: 173–182.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Zoumbos NC et al. High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transplant 2013; 19: 75–81.

    Article  CAS  PubMed  Google Scholar 

  18. Kumar AJ, Hexner EO, Frey NV, Luger SM, Loren AW, Reshef R et al. Pilot study of prophylactic ex vivo costimulated donor leukocyte infusion after reduced-intensity conditioned allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19: 1094–1101.

    Article  PubMed  Google Scholar 

  19. El-Jurdi N, Reljic T, Kumar A, Pidala J, Bazarbachi A, Djulbegovic B, Kharfan-Dabaja MA . Efficacy of adoptive immunotherapy with donor lymphocyte infusion in relapsed lymphoid malignancies. Immunotherapy 2013; 5: 457–466.

    Article  CAS  PubMed  Google Scholar 

  20. Frey NV, Porter DL . Graft-versus-host disease after donor leukocyte infusions:presentation and management. Best Pract Res Clin Haematol 2008; 21: 205–222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ma SY, Au WY, Lie AK, Ng IO, Leung AY, Tse EW et al. Liver graft-versus-host disease after donor lymphocyte infusion for relapses of hematologic malignancies post allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2004; 34: 57–61.

    Article  CAS  PubMed  Google Scholar 

  22. Akpek G, Boitnott JK, Lee LA, Hallick JP, Torbenson M, Jacobsohn DA et al. Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion. Blood 2002; 100: 3903–3907.

    Article  CAS  PubMed  Google Scholar 

  23. Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23: 1993–2003.

    Article  PubMed  Google Scholar 

  24. Ringdén O, Labopin M, Gorin NC, Schmitz N, Schaefer UW, Prentice HG et al. Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia? Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol. 2000; 111: 1130–1137.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department Dermatology, University Hospital Birmingham NHS Trust, Birmingham, UK

    J J Scarisbrick

  2. Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK

    F L Dignan & E Tholouli

  3. Department of Haematology, Nottingham University Hospitals NSH Trust, Nottingham, UK

    S Tulpule & E D Gupta

  4. Department of Haematology, The Royal Marsden NHS Foundation Trust, Surrey, UK

    S Kolade & B Shaw

  5. Department of Statistics, University Hospital Birmingham NHS Trust, Birmingham, UK

    F Evison

  6. Department of Haematology, King’s College Hospital, London, UK

    G Shah, G Mufti, A Pagliuca & K Raj

  7. Department Haematology, University Hospital Birmingham NHS Trust, Birmingham, UK

    R Malladi

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  1. J J Scarisbrick
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Correspondence to J J Scarisbrick.

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Scarisbrick, J., Dignan, F., Tulpule, S. et al. A multicentre UK study of GVHD following DLI: Rates of GVHD are high but mortality from GVHD is infrequent. Bone Marrow Transplant 50, 62–67 (2015). https://doi.org/10.1038/bmt.2014.227

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  • DOI: https://doi.org/10.1038/bmt.2014.227

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