Use of infliximab‐daclizumab combination for the treatment of acute and chronic graft‐versus‐host disease of the liver and gut

Rodriguez, Vilmarie; Anderson, Peter M.; Trotz, B.; Arndt, Carola A.S.; Allen, Julia A.; Khan, Shakila P.

doi:10.1002/pbc.20648

Cited by 25 publications

(14 citation statements)

References 17 publications

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“…These antibodies have shown modest success independently in achieving durable responses against SR- GVHD (10) (11) (12) (13). Concurrent use of these agents was evaluated in a small number of patients receiving non-myeloablative HCT, and resulted in superior survival compared to patients on an ATG-based regimen (14) (15). In an attempt to enhance response and improve prognosis, we have used a combination of anti-cytokine therapy and report our experience treating 17 patients with SR-GVHD with combination daclizumab and infliximab.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD

Rager

Frey

Goldstein

et al. 2010

Bone Marrow Transplant

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Treatment options for steroid-refractory GVHD (SR-GVHD) are unsatisfactory and prognosis is poor. Inflammatory cytokines IL-2 and TNF-α are important mediators of GVHD, and may be critical targets for therapy. We retrospectively reviewed our experience using combination anti-cytokine therapy of daclizumab and infliximab. Seventeen evaluable patients had a median age of 47 years (range 35–63). The conditioning regimen was myeloablative in 13 and nonmyeloablative in 4 cases. GVHD occurred a median of 49 days after transplant in 12 patients (range 21–231) and a median of 46 days (range 25–119) after donor lymphocyte infusion in 5 patients. All patients had persistent or progressive GVHD despite 1–2 mg/kg/day of corticosteroids for a median of 7 days (range 2–26). They received combination daclizumab and infliximab for acute GVHD IBMTR severity index B (3), C (10) or D (4). 47% of patients responded; 24% had complete resolution of symptoms and 24% had partial responses. Survival was limited and all died a median of 6.7 months (range 1.6–26) from transplant and 35 days from initiation of daclizumab/infliximab. This retrospective analysis suggests that combination anti-cytokine therapy with daclizumab/infliximab has significant activity in SR-GVHD, but outcomes remain poor. New methods to prevent and treat GVHD are urgently needed.

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Section: Introductionmentioning

confidence: 99%

Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD

Rager

Frey

Goldstein

et al. 2010

Bone Marrow Transplant

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“…Due to these promising results, experimental infliximab treatment has been transferred to the field of organ transplantation. In several case reports, infliximab has been shown to be a therapeutic option for acute rejection, especially in patients with refractory rejection (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Pech

Finger

Fujishiro

et al. 2010

American Journal of Transplantation

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As we have shown in the past, acute rejection-related TNF-a upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-a antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (

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“…2,3 This being the case, it comes as no surprise that treatment of acute GVHD is rather unsuccessful and has made little or no progress in the past 30 years. 4 This is true for conventional immunosuppression with steroids and anti-thymocyte globulin (ATG), 5 as well as for MoABs directed against IL2 receptors, TNF or ABX, [6][7][8][9][10] with one recent exception: 11 it should be noted that in a recent CIBMTR (Center for International Blood and Marrow Transplant Research) trial, etanercept has not proven to be superior to mycophenolate, in combination with steroids (unpublished).…”

Section: Introductionmentioning

confidence: 99%

Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants

Bacigalupo

Lamparelli

Milone

et al. 2009

Bone Marrow Transplant

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We have previously shown that hemopoietic stem cell transplant (HSCT) recipients can be stratified on day þ 7 as having low, intermediate or a high risk of transplantrelated mortality (TRM). With the aim of reducing TRM and GVHD, intermediate and high-risk patients (n ¼ 170) were randomized to receive anti-thymocyte globulin (ATG, thymoglobuline) on day þ 7 (n ¼ 84) or no treatment (n ¼ 86) (controls). There was a reduction of TRM from 35% in controls to 29% in ATG patients (P ¼ 0.3), of acute GVHD III-IV from 15 to 5% (P ¼ 0.02) and of chronic GVHD from 26 to 11% (P ¼ 0.03); survival was comparable. The predictive value of the day þ 7 score on TRM was confirmed for controls (19 vs 42% for intermediate vs high risk, respectively, P ¼ 0.03), whereas ATG abrogated this predictive effect (29 vs 29%). ATG reduced GVHD (P ¼ 0.006) in high-risk patients, but not in patients with an intermediate risk.In conclusion, we confirm that TRM can be predicted on the basis of day þ 7 laboratory values, after alternative donor HSCT; in high-, but not intermediate-risk patients, the administration of ATG on day þ 7 reduces GVHD. These results may represent a platform for risk-adapted post transplant immune modulation.

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Use of infliximab‐daclizumab combination for the treatment of acute and chronic graft‐versus‐host disease of the liver and gut

Cited by 25 publications

References 17 publications

Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD

Inflammatory cytokine inhibition with combination daclizumab and infliximab for steroid-refractory acute GVHD

Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants

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