Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-Versus-Host Disease

Lymphodepleting chemotherapy with donor lymphocyte infusion post-allogeneic HCT for hematological malignancies is associated with severe, but therapy-responsive aGvHD

Abstract

Donor lymphocyte infusion (DLI) is an option for relapsed hematologic malignancies or incomplete chimerism of non-malignant diseases following allogeneic hematopoietic cell transplantation (HCT). We analyzed the incidence of acute GvHD (aGvHD) in patients treated with DLI. From 1995 to 2013, 171 DLIs were given to 120 patients. The cumulative incidence of post-DLI grade II–IV aGvHD was 33% (CI 25–42%, n=40; 12 grade II), and of grade III–IV 24% (CI 16–32%, n=28). GvHD after DLI (n=46) involved the skin in 70% (n=32), lower gastrointestinal (GI) 65% (n=30), upper GI 43% (n=20) and liver 35% (n=16). Patients receiving chemotherapy accompanying the DLI (chemo-DLI) (n=37) had more frequent aGvHD and particularly lower GI GvHD. Risk factors for grade II–IV aGvHD included age >40, chemo-DLI, malignant disease and time from HCT to DLI <200 days. aGvHD response to treatment at 8 weeks was complete in 40% and complete/partial (CR/PR) in 52%. Chemo-DLI had higher response rates to aGVHD treatment in non-CML malignancies. We observed frequent, yet therapy-responsive aGvHD following DLI. GI GvHD in particular is a significant risk when giving chemotherapy prior to DLI. Improvements in DLI efficacy and GvHD management are still needed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  2. Schmid C, Labopin M, Nagler A, Bornhäuser M, Finke J, Fassas A et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working party. J Clin Oncol 2007; 25: 4938–4945.

    Article  CAS  PubMed  Google Scholar 

  3. Collins RH, Goldstein S, Girait S, Levine J, Porter D, Drobyski W et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 2000; 26: 511–516.

    Article  PubMed  Google Scholar 

  4. Frugnoli I, Cappelli B, Chiesa R, Biral E, Noè A, Evangelio C et al. Escalating doses of donor lymphocytes for incipient graft rejection following SCT for thalassemia. Bone Marrow Transplant 2010; 45: 1047–1051.

    Article  CAS  PubMed  Google Scholar 

  5. Jagasia M, Arora M, Mary ED, Chao NJ, McCarthy PL, Cutler CS et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 2012; 119: 296–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Apperley JF, Mauro FR, Goldman JM, Gregory W, Arthur CK, Hows J et al. Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect. Br J Haematol 1988; 69: 239–245.

    Article  CAS  PubMed  Google Scholar 

  7. 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 

  8. Fine JP, Gray RJ . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

  9. 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 

  10. Macmillan ML, Weisdorf DJ, Wagner JE, DeFor TE, Burns LJ, Ramsay NK et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease. Biol Blood Marrow Transplant 2002; 8: 387–394.

    Article  CAS  PubMed  Google Scholar 

  11. Martin PJ, Schoch G, Fisher L, Byers V, Anasetti C, Appelbaum FR et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 1990; 76: 1464–1472.

    CAS  PubMed  Google Scholar 

  12. Warlick ED, DeFor T, Blazar BR, Burns L, Verneris MR, Ustun C et al. Successful remission rates and survival after lymphodepleting chemotherapy and donor lymphocyte infusion for relapsed hematologic malignancies postallogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18: 480–486.

    Article  PubMed  Google Scholar 

  13. MacMillan ML, Robin M, Harris AC, DeFor TE, Martin PJ, Alousi A et al. A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transplant 2015; 21: 761–767.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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 

  15. Yan CH, Wang JZ, Liu DH, Zu LP, Chen H, Liu KY et al. Chemotherapy followed by modified donor lymphocyte infusion as a treatment for relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion: superior outcomes compared with chemotherapy alone and an analysis of prognostic factors. Eur J Haematol 2013; 91: 304–314.

    Article  CAS  PubMed  Google Scholar 

  16. Posthuma EF, Marijt EW, Barge RM, van Soest RA, Baas IO, Starrenburg CW et al. Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease. Biol Blood Marrow Transplant 2004; 10: 204–212.

    Article  CAS  PubMed  Google Scholar 

  17. Eefting M, von dem Borne PA, de Wreede LC, Halkes CJ, Kersting, Marijt EW et al. Intentional donor lymphocyte induced limited acute graft versus host disease is essential for long-term survival of relapsed acute myeloid leukemia after allogeneic stem cell transplantation. Haematologica 2014; 99: 751–758.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Porter DL, Levine BL, Bunin N, Stadtmauer EA, Luger SM, Goldstein S et al. A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood 2006; 107: 1325–1331.

    Article  CAS  PubMed  Google Scholar 

  19. Traversari C, Marktel S, Magnani Z, Mangia P, Russo V, Ciceri F et al. The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood 2007; 109: 4708–4715.

    Article  CAS  PubMed  Google Scholar 

  20. Ivanov R, Hol S, Aarts T, Hagenbeek A, Slager EH, Ebeling S . UTY-specific TCR-transfer generates potential graft-versus-leukaemia effector T cells. Br J Haematol 2005; 129: 392–402.

    Article  CAS  PubMed  Google Scholar 

  21. Curley C, Hill GR, McLean A, Kennedy GA . Immunotherapy following relapse of acute leukaemia after T-cell-replete allogeneic peripheral blood progenitor cell transplantation: importance of new onset of chronic graft-versus-host disease. Int J Lab Hematol 2014; 36: 197–204.

    Article  CAS  PubMed  Google Scholar 

  22. Chalandon Y, Passweg JR, Schmid C, Olavarria E, Dazzi F, Simula MP et al. Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the Chronic Leukemia Working Party of the EBMT. Bone Marrow Transplant 2010; 45: 558–564.

    Article  CAS  PubMed  Google Scholar 

  23. Sorror ML, Martin PJ, Storb RF, Bhatia S, Maziarz RT, Pulsipher MA et al. Pretransplant cormorbidities predict severity of acute graft-versus-host disease and subsequent mortality. Blood 2014; 124: 287–295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Passweg JR, Baldomero H, Gratwohl A, Bregni M, Cesaro S, Dreger P et al. The EBMT activity survey: 1990–2010. Bone Marrow Transplant 2012; 47: 906–923.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Corresponding author

Correspondence to F He.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, F., Warlick, E., Miller, J. et al. Lymphodepleting chemotherapy with donor lymphocyte infusion post-allogeneic HCT for hematological malignancies is associated with severe, but therapy-responsive aGvHD. Bone Marrow Transplant 51, 1107–1112 (2016). https://doi.org/10.1038/bmt.2016.63

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/bmt.2016.63

This article is cited by

Search

Quick links