Severe acute graft-versus-host disease after T-cell depleted allogeneic stem cell graft from a second donor caused by persisting T-cells from the first donor

Wiesmann, Anne; Bader, Peter; Bamberg, M.; Faul, Christoph; Kanz, Lothar; Einsele, Hermann

doi:10.1038/sj.bmt.1704170

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Chimerism analysis of the gut biopsy is not available in this patient. The persistence of allogeneic donor cells at a time when no evidence of donor cells was detected in blood and marrow may mean that GvHDinducing cells persist in affected tissue 13,14 after elimination from blood or marrow.…”

Section: Resultsmentioning

confidence: 99%

Autologous/syngeneic stem cell transplantation to treat refractory GvHD

Passweg

Orchard

Buergi

et al. 2004

Bone Marrow Transplant

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Section: Resultsmentioning

confidence: 99%

Autologous/syngeneic stem cell transplantation to treat refractory GvHD

Passweg

Orchard

Buergi

et al. 2004

Bone Marrow Transplant

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“…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.…”

mentioning

confidence: 99%

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

Üstün

Jillella

Shah

et al. 2010

Bone Marrow Transplant

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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 weeks 6 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.A 31-year-old man with wt loss and bone pain in his legs, presented with a WBC count 6.7 Â 10 9 /l, 14% blasts, hemoglobin 9.8 g per 100 ml, and plt count 154 000 Â 10 9 /l. A BM biopsy revealed 4 þ reticulin fibrosis and 16% myeloblasts, consistent with advanced stage primary myelofibrosis. He was initially treated with lenalidomide and then a panhistone deacetylase inhibitor (LBH589). He received an HCT from his 22-year-old brother after treatment with melphalan (140 mg/m 2 ) and fludarabine (120 mg/m 2 ). He was treated with tacrolimus (0.03 mg/kg/day i.v. continuous infusion), initiated day À2 and mycophenolate mofetil (1 g i.v. b.i.d.) initiated day 0. He received G-CSF, acyclovir, fluconazole and levofloxacin. On day þ 7, he developed clinical grade III gut GVHD (1.5-2 l/d of diarrhea). Four days after initiating treatment with methylprednisolone (1 mg/kg i.v. b.i.d.) and total parenteral nutrition, his symptoms resolved. Neutrophil and plt engraftment occurred on days þ 10 and þ 42, respectively. Chimerism analysis revealed 100% donor-derived cells on day þ 14. Steroids were tapered off within 4 months. At 5 months post transplant, he developed recurrent gut GVHD with severe abdominal pain and 1.5 l of diarrhea per day. Colonic biopsy revealed extensive mucosal ulceration and complete crypt loss, consistent with severe (grade IV) acute GVHD (Figure 1). High-dose therapy with methylprednisolone, infliximab (anti-TNF) and daclizumab (anti-IL-2) did not improve GVHD. Severe gut GVHD persisted despite sequential treatment with extracorporeal photopheresis, rituximab, CY and pentostatin.A second HCT from another donor for treatment of steroidresistant GVHD was proposed to him and his family. Although this approach had not been used for this purpose, previously, he offered his consent for the procedure, and our institutional ethical committee approved the second transplant. He received a second transplant from his HLAidentical youngest brother (13 years old) 3 months after recurrence of gut GVHD. The conditioning regimen consisted of CY (60 mg/...

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Severe acute graft-versus-host disease after T-cell depleted allogeneic stem cell graft from a second donor caused by persisting T-cells from the first donor

Cited by 2 publications

References 10 publications

Autologous/syngeneic stem cell transplantation to treat refractory GvHD

Autologous/syngeneic stem cell transplantation to treat refractory GvHD

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

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