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Second allo-SCT from a different donor can improve severe steroid-resistant gut GVHD

Bone Marrow Transplantation volume 45, pages 1658–1660 (2010)Cite this article

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GVHD leads to increased morbidity and mortality after allogeneic hematopoietic SCT (HCT).1 Compared with myeloablative regimens (MARs), nonmyeloablative conditioning regimens do not appear to decrease the rate of serious GVHD.2 In steroid-resistant patients, various immunosuppressive agents including antibodies against IL-2 and TNF have been attempted.3, 4, 5 Outcome is very poor in patients who do not respond second-line treatment, in particular, if they have gut GVHD. Non-relapse mortality was 71% at 1-year post-HCT in patients with steroid-refractory gut GVHD.6 Survival rate decreases to 16% in adults not responding to steroids within 2 weeks6 or 0% in adults and children not responding to a combination of anti-IL-2 and anti-TNF.3, 4 A second HCT from another donor could improve gut GVHD in mice.7 We performed an HCT from a second HLA-matched sibling for treatment of severe acute gut GVHD in a patient in whom all other therapeutic approaches had been exhausted.

This case report shows that severe gut GVHD can improve after a second HCT from a different donor. However, our patient died with toxicity most like caused by the second conditioning regimen. The optimal conditioning regimen before a second HCT for this indication is unknown because it has been done for graft failure or relapse. First donor lymphocytes could persist and cause severe acute GVHD even after a second HCT from a different donor.8 MAR have the potential advantage of eliminating pathogenic lymphocytes from the first donor, and T cells from the second donor might also help eliminate lymphocytes from the first donor. Some patients can tolerate myeloablative conditioning regimens before a second transplant for treatment of recurrent malignancy,9 but the risk of regimen-related toxicity is very high, especially in patients who have severe GVHD complicated by poor nutrition. As an alternative, nonmyeloablative conditioning regimens have also been used successfully for second HCT in patients who rejected a prior allograft from a different donor.10 We used a MAR in our patient, because he had no active infection and had a good performance status.

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References

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Acknowledgements

We thank the family of the late Adolfo Garcia for permission to report this case. We also thank the following individuals for their great contribution that made possible the second transplantation for the first time: Julie Neal, RN; Alan Roberts, MD; James Wynn, MD; Roger Vega, MD; Kavita Natarajan, MD; Lloyd Cook, MD; Adil Degani, MD; Sandra Helman, PhD; Emily Moore, RN; Helen Fain, RN; Richard Sattin, MD.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology and Bone Marrow Transplantation, Medical College of Georgia, Augusta, GA, USA

    C Ustun, A Jillella, R Shah, K Sterling & F Awan

  2. University of Georgia, College of Pharmacy, Athens, GA, USA

    D Deremer

  3. Department of Pathology, Augusta, GA, USA

    N Savage

  4. Section of Pulmonary and Critical Care, Augusta, GA, USA

    J R Gossage & T Dillard

  5. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    P J Martin

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  1. C Ustun
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Correspondence to C Ustun.

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Ustun, C., Jillella, A., Shah, R. et al. Second allo-SCT from a different donor can improve severe steroid-resistant gut GVHD. Bone Marrow Transplant 45, 1658–1660 (2010). https://doi.org/10.1038/bmt.2010.17

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