A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease

Carpenter, Paul A.; Appelbaum, Frederick R.; Corey, Lawrence; Deeg, H. Joachim; Doney, K; Gooley, Theodore A.; Krueger, James G.; Martin, Paul J.; Pavlovic, Sandra; Sanders, Jean E.; Slattery, John T.; Levitt, Daniel; Storb, Rainer; Woolfrey, Ann E.; Anasetti, Claudio

doi:10.1182/blood.v99.8.2712

Cited by 161 publications

(75 citation statements)

References 36 publications

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“…Additionally, OS reported here is within the range of reported survival among alternative agents used for steroidrefractory aGVHD. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] MMF was overall well tolerated, with the majority of those treated here remaining on therapy without dose reduction or significant adverse events directly referable to this agent; only two patients required discontinuation of MMF on account of myelosuppression. However, though a direct causal role cannot be assigned to MMF, the overall burden of immunosuppression and related infectious complications certainly contributed to the morbidity and mortality seen in this series.…”

Section: Discussionmentioning

confidence: 99%

“…5,[8][9][10][11] A number of therapeutic agents directed at the immune cascade underlying aGVHD have shown modest activity in steroid-refractory aGVHD. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Mycophenolate mofetil (MMF), whose metabolite mycophenolic acid inhibits the de novo synthesis of purines in lymphocytes, has probable efficacy in the treatment of aGVHD, based on three small case series that cumulatively reported 17 cases in which MMF was used for initial therapy for aGVHD, and 16 cases with glucocorticoidrefractory aGVHD. [31][32][33] Here, we report outcomes in a series of 27 recipients of allogeneic hematopoietic cell transplantation treated with MMF as salvage therapy for steroid-refractory aGVHD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

Pidala

Kim

Perkins

et al. 2009

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

Pidala

Kim

Perkins

et al. 2009

Bone Marrow Transplant

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“…32 Anti-T-cell antibodies such as antithymocyte globulins have been used for pre-emptive treatment of AGVHD in high-risk patients. 33 Monoclonal antibodies directed against activated T cells such as visilizumab 34 or ABX-CBL 35 have been used successfully to treat steroid-refractory AGVHD. The use of anticytokines in AGVHD has thus far been disappointing, mainly because of initiating therapy at advanced stages and recurrence of AGVHD after stopping the treatment.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation

et al. 2003

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Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and 4grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, Po0.001), between days 0-5 post-BMT (IL-6 and IL-8, Po0.05) and days 6-10 (L-6, Po0.001; IL-8 and TNF, Po0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0-5 were associated (P ¼ 0.044) with early (o40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odd's ratio: 2.3 [1.2-4.5], P ¼ 0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.

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“…One treatment option is based on drugs, which are directly cytotoxic to the effector cells of aGVHD (ATG, OKT3, visilizumab, mycophenolate mofetil (MMF), pentostatin, sirolimus, anti-CD147, photopheresis). [2][3][4][5][6][7][8][9][10][11][12][13] A different approach is based on blockage of cytokines involved in the pathogenesis of aGVHD (antibodies against TNF and IL-2 or IL-1 antagonist).…”

mentioning

confidence: 99%

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

Wolff

Roessler

Steiner

et al. 2005

Bone Marrow Transplant

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Summary:Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNFreceptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m 2 s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15-61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n ¼ 6), HLAmatched unrelated (n ¼ 14), and HLA-mismatched unrelated (n ¼ 1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185-1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n ¼ 11) or organ failure due to aGVHD (n ¼ 3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, longterm mortality due to infectious complications and chronic GVHD remains high.

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A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease

Cited by 161 publications

References 36 publications

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

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