Abstract
Acute GVHD (aGVHD) remains a major cause of mortality in patients undergoing allo-SCT. In particular, the outcome of those patients who fail first-line therapy with glucocorticosteroids is poor. Preliminary reports suggested that the purine analogue pentostatin might be effective for treatment of steroid-refractory aGVHD. Here, we report on our single-center experience with pentostatin in this condition. From 2005 to 2008, a total of 24 consecutive patients, who had undergone first-line salvage treatment for steroid-refractory aGVHD of the gastrointestinal tract with pentostatin, were identified from 301 patients allografted during that period and retrospectively analyzed. Response to treatment, defined as CR or very good PR (VGPR), was observed in nine patients (38%), with a median time to response of 10 days. Although pentostatin was associated with only moderate myelosuppressive toxicity, if any, 2-year survival was only 17% with five of the nine responders dying from infection (four patients) or recurrent GVHD (one patient). We conclude that pentostatin is a moderately effective therapy for steroid-refractory aGVHD, showing response and outcome rates similar to other clinically used regimens.
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References
Van Lint MT, Milone G, Leotta S, Uderzo C, Scime R, Dallorso S et al. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood 2006; 107: 4177–4181.
Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood 2008; 111: 2470–2475.
Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB . Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant 2002; 8: 155–160.
Welniak LA, Blazar BR, Murphy WJ . Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol 2007; 25: 139–170.
Kolb HJ . Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 2008; 112: 4371–4383.
Edinger M, Powrie F, Chakraverty R . Regulatory mechanisms in graft-versus-host responses. Biol Blood Marrow Transplant 2009; 15 (Suppl 1): 2–6.
Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL . Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood 1997; 90: 3204–3213.
Nikolic B, Lee S, Bronson RT, Grusby MJ, Sykes M . Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ target. J Clin Invest 2000; 105: 1289–1298.
Luft T, Conzelmann M, Benner A, Rieger M, Hess M, Strohhaecker U et al. Serum cytokeratin-18 fragments as quantitative markers of epithelial apoptosis in liver and intestinal graft-versus-host disease. Blood 2007; 110: 4535–4542.
He S, Cao Q, Qiu Y, Mi J, Zhang JZ, Jin M et al. A new approach to the blocking of alloreactive T-cell mediated graft-versus-host disease by in vivo administration of anti-CXCR3 neutralizing antibody. J Immunol 2008; 181: 7581–7592.
Spiers AS . Pentostatin (2prime prime or minute-deoxycoformycin): clinical pharmacology, role in cancer chemotherapy, and future prospects. Am J Ther 1995; 2: 196–216.
Resta R, Thompson LF . SCID: the role of adenosine deaminase deficiency. Immunol Today 1997; 19: 533–534.
Hershfield MS . New insights into adenosine-receptor-mediated immunosuppression and the role of adenosine in causing the immunodeficiency associated with adenosine deaminase deficiency. Eur J Immunol 2005; 35: 31–41.
Brown JB, Lee G, Grimm GR, Barrett TA . Therapeutic benefit of pentostatin in severe IL-10−/− colitis. Inflamm Bowel Dis 2008; 14: 880–887.
Döhner H, Ho AD, Thaler J, Stryckmans P, Sonneveld P, de Witte T et al. Pentostatin in prolymphocytic leukemia: phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group. J Natl Cancer Inst 1993; 85: 658–662.
Ho AD, Suciu S, Stryckmans P, De Cataldo F, Willemze R, Thaler J et al. Pentostatin in T-cell malignancies—a phase II trial of the EORTC. Leukemia Cooperative Group. Ann Oncol 1999; 10: 1493–1498.
Epstein J, Bealmear PM, Kennedy DW, Herrmann MJ, Islam A, Wiedl SC . Prevention of graft-versus-host disease in allogeneic bone marrow transplantation by pretreatment with 2′-deoxycoformycin. Exp Hematol 1986; 14: 845–849.
Bolaños-Meade J, Jacobsohn DA, Margolis J, Ogden A, Wientjes G, Byrd JC et al. Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol 2005; 23: 2661–2668.
Klein S, Mousset S, Bug G, Wassmann B, Martin H . Long-Term follow up of a phase II study of pentostatin in patients with steroid refractory acute intestinal graft-versus-host disease. Bone Marrow Transplant 2008; 41 (Suppl 1): S222 (abstract 773).
Przepiorka JD, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.
Vigorito AC, Campregher PV, Storer BE, Carpenter PA, Moravec CK, Kiem HP et al. Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD. Blood 2009; 114: 702–708.
Martin PJ, Bachier CR, Klingemann HG, McCarthy PL, Szabolcs P, Uberti JP et al. Endpoints for clinical trials testing treatment of acute graft-versus-host disease: a joint statement. Biol Blood Marrow Transplant 2009; 15: 777–784.
Knop S, Hebart H, Gscheidle H, Holler E, Kolb HJ, Niederwieser D et al. OKT3 muromonab as second-line and subsequent treatment in recipients of stem cell allografts with steroid-resistant acute graft-versus-host disease. Bone Marrow Transplant 2005; 36: 831–837.
Knop S, Hebart H, Gratwohl A, Kliem C, Faul C, Holler E et al. Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party. Leukemia 2009; 21: 1830–1833.
Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood 2000; 95: 83–89.
Massenkeil G, Rackwitz S, Genvresse I, Rosen O, Dörken B, Arnold R . Basiliximab is well tolerated and effective in the treatment of steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation. Bone Marrow Transplant 2002; 30: 899–903.
Couriel D, Saliba R, Hicks K, Ippoliti C, de Lima M, Hosing C et al. Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood 2004; 104: 649–654.
Pidala J, Kim J, Field T, McBride A, Kharfan-Dabaja M, Perkins J et al. Infliximab for managing steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant 2009; 15: 1116–1121.
Perfetti P, Carlier P, Strada P, Gualandi F, Occhini D, Van Lint MT et al. Extracoporeal photopheresis for the treatment of steroid refractory acute GVHD. Bone Marrow Transplant 2008; 42: 609–617.
Greinix HT, Knobler RM, Worel N, Schneider B, Schneeberger A, Hoecker P et al. The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica 2006; 91: 405–408.
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371: 1579–1586.
Von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K et al. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 2009; 43: 245–251.
Martin PJ, Uberti JP, Soiffer RJ, Klingemann H, Waller EK, Daly AS et al. Prochymal improves response rates in patients with steroid-refractory acute graft versus host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter phase III trial in GVHD. Biol Blood Marrow Transplant 2010; 16 (Suppl. 2): 169–170.
Paczesny S, Krijanovski OI, Braun TM, Choi SW, Clouthier SG, Kuick R et al. A biomarker panel for acute graft-versus-host disease. Blood 2009; 113: 273–278.
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Schmitt, T., Luft, T., Hegenbart, U. et al. Pentostatin for treatment of steroid-refractory acute GVHD: a retrospective single-center analysis. Bone Marrow Transplant 46, 580–585 (2011). https://doi.org/10.1038/bmt.2010.146
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DOI: https://doi.org/10.1038/bmt.2010.146
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