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.

  • Correspondence
  • Published:

Reversal of severe graft-versus-host disease after nonmyeloablative matched unrelated donor stem cell transplant by infusion of backup autologous peripheral blood stem cells

Bone Marrow Transplantation volume 36, pages 267–268 (2005)Cite this article

Acute graft-versus-host disease (aGVHD) is a major concern in stem cell transplantation and is associated with significant morbidity and mortality.1, 2 We report a successful use of infusion of autologous peripheral blood stem cells (ASC) to treat severe, refractory grade 4 aGVHD after a nonmyeloablative matched unrelated donor (MUD) transplant. A 55-year-old white female presented in December 2000 with pain and pathological fracture of the left humerus and was diagnosed with multiple myeloma. Her bone marrow biopsy revealed 100% cellularity with 60% abnormal plasma cells, which were kappa light chain restricted. Cytogenetic studies revealed normal chromosomes. She had low immunoglobulins and serum M-spike of 0.1 gm/dl, and no Bence-Jones protein in the urine. Skeletal survey and CT scans of the chest, abdomen and pelvis showed diffuse multiple boney lytic lesions. Beta 2-microglobulin was 1.67 mg/dl. The patient was initially treated with one cycle of melphalan and prednisone while receiving radiation therapy. Subsequently, she received four cycles of VAD and one cycle of hyper-CVAD before receiving autologous stem cell transplantation (ASCT) in June 2001. She also received monthly infusion of pamidronate. Disease evaluation at 6 weeks post-ASCT showed progression of the disease. She then received a series of salvage therapies including 4 months of thalidomide, thalidomide and oral melphalan, palliative XRT for a new lumbosacral lesion, and three cycles of chemotherapy with lomustine, etoposide, cyclophosphamide, and prednisone, but all with transient or minimal response. She then underwent a nonmyeloablative MUD transplant on 07/10/02. Her conditioning regimen consisted of Fludarabine, ATGAM (horse antithymocyte globulin (ATG)), and busulfan. The fludarabine was given at 30 mg/m2/day on day −7 through day −2, ATGAM at 10 mg/kg/day on days −6 through day −3, and busulfan dose was 8 mg/kg in eight divided doses q 6 h. FK-506 was started on day −1 at 3 mg p.o. b.i.d. for GVHD prophylaxis.

The incidence of grade II–IV acute GVHD is 78% and grade III–IV is 24% after HLA MUD transplant.3 Corticosteroids are the mainstay of therapy for aGVHD. Unfortunately, the rate of achieving a durable response with steroids is about 50%.4 The outcome of those developing steroid-refractory disease is poor, with 60–80% dying from GVHD-related causes.1 Commonly used salvage agents include ATG, MMF, sirolimus, PUVA, and Daclizumab.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

References

  1. Schwartz JM, Wolford JL, Thornquist MD et al. Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987–1997: incidence, causes, and outcome. Am J Gastroenterol 2001; 96: 385–393.

    CAS  PubMed  Google Scholar 

  2. Arai S, Margolis J, Zahurak M et al. Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant 2002; 8: 155–160.

    Article  PubMed  Google Scholar 

  3. Nademanee A, Schmidt GM, Parker P et al. The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate, and prednisone. Blood 1995; 86: 1228–1234.

    CAS  PubMed  Google Scholar 

  4. Van Lint MT, Uderzo C, Locasciulli A et al. Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood 1998; 92: 2288–2293.

    CAS  PubMed  Google Scholar 

  5. Ricordi C, Tzakis AG, Zeevi A et al. Reversal of graft-versus-host disease with infusion of autologous bone marrow. Cell Transplant 1994; 3: 187–192.

    Article  CAS  PubMed  Google Scholar 

  6. Passweg JR, Orchard K, Buergi A et al. Autologous/syngeneic stem cell transplantation to treat refractory GvHD. Bone Marrow Transplant 2004; 34: 995–998.

    Article  CAS  PubMed  Google Scholar 

  7. Pusic I, Pavletic SZ, Kessinger A et al. Pseudoautologous blood stem cell transplantation for refractory chronic graft-versus-host disease. Bone Marrow Transplant 2002; 29: 709–710.

    Article  CAS  PubMed  Google Scholar 

  8. Weiss L, Slavin S . Prevention and treatment of graft-versus-host disease by down-regulation of anti-host reactivity with veto cells of host origin. Bone Marrow Transplant 1999; 23: 1139–1143.

    Article  CAS  PubMed  Google Scholar 

  9. Kuwana M, Kaburaki J, Wright TM et al. Induction of antigen-specific human CD4(+) T cell anergy by peripheral blood DC2 precursors. Eur J Immunol 2001; 31: 2547–2557.

    Article  CAS  PubMed  Google Scholar 

  10. Hoffmann P, Ermann J, Edinger M et al. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 2002; 196: 389–399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Florida, Gainesville, FL, USA

    S A Khan & J S Moreb

Authors
  1. S A Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J S Moreb
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, S., Moreb, J. Reversal of severe graft-versus-host disease after nonmyeloablative matched unrelated donor stem cell transplant by infusion of backup autologous peripheral blood stem cells. Bone Marrow Transplant 36, 267–268 (2005). https://doi.org/10.1038/sj.bmt.1705033

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705033

Search

Advanced search

Quick links