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

Knop, Stefan; Hebart, Holger; Gratwohl, Aloïs; Kliem, Constanze; Faul, Christoph; Holler, Ernst; Apperley, Jane F.; Kolb, Hans Jochem; Schaefer, A.T; Niederwieser, Dietger; Einsele, Hermann

doi:10.1038/sj.leu.2404731

Cited by 23 publications

(17 citation statements)

References 8 publications

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“…23 A slight advantage of addition of OKT3 to high-dose steroids has been confirmed in a subsequent phase III trial. 24 Other phase II studies that addressed blocking of proinflammatory cytokines (for example, TNF-a and IL-2) with MoAbs resulted in overall CR rates of 47, 53 and 62% for daclizumab, basiliximab and infliximab, respectively. [25][26][27] In the study by Przepiorka et al using daclizumab, a specific CR rate of 37% was reported for GI GVHD.…”

Section: Discussionmentioning

confidence: 99%

Pentostatin for treatment of steroid-refractory acute GVHD: a retrospective single-center analysis

Schmitt

Luft

Hegenbart

et al. 2010

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 99%

Pentostatin for treatment of steroid-refractory acute GVHD: a retrospective single-center analysis

Schmitt

Luft

Hegenbart

et al. 2010

Bone Marrow Transplant

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“…The authors concluded that MP 2 mg/kg/day is as effective as a higher dose in treating aGVHD, and patients who do not respond to standard dose MP (2 mg/kg/day) should receive therapy other than corticosteroids. 19 In a randomized trial, Knop et al 20 treated adult patients with steroid-resistant aGVHD with MP 10 mg/kg plus OKT3 vs MP 10 mg/kg alone. Only 7 out of the 40 (18%) patients who received high-dose MP alone were alive without aGVHD on day 100 compared to 33% of patients who had received high-dose MP and OKT3.…”

Section: Discussionmentioning

confidence: 99%

Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD

Schechter

Macartney²,

Finkelstein

et al. 2010

Bone Marrow Transplant

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Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (X20 mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had Xgrade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.

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“…The toxicity of OKT3 includes cytokine release syndrome (fever, chills, nausea and rash) in 60% of treated patients. In a recent randomized study of 80 patients with steroid-refractory GVHD, comparing OKT3 plus high-dose methylprednisolone (10 mg/kg) versus high-dose methylprednisolone alone, there was no significant difference in overall response rate at day 100 (53 vs 33%; p = 0.06) or overall survival at 1 year (45 vs 36%; p = 0.61) [204]. To minimize cytokine-release syndrome, a humanized anti-CD3 antibody (that does not bind human Fc receptor), visilizumab (HuM291), was evaluated in Phase I and II studies.…”

Section: Salvage Therapy For Gvhdmentioning

confidence: 99%

Current and future approaches for control of graft-versus-host disease

Koreth¹,

Antin

2008

Expert Review of Hematology

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Graft-versus-host disease (GVHD), both acute and chronic, remains one of the major barriers to improving outcomes after allogeneic stem cell transplantation. The pathophysiology of GVHD is complex and incompletely understood. GVHD is believed to arise from the interaction of: tissue damage and proinflammatory cytokines causing activation of antigen-presenting cells (APCs, donor T-cell activation by APCs and cytokines and host tissue injury by effector T lymphocytes and proinflammatory cytokines. There is also a role for additional lymphocyte subtypes (naive and memory T cells, regulatory T cells, natural killer T cells and B cells) in GVHD pathogenesis. Strategies to improve donor-recipient HLA match, and to minimize conditioning toxicity, cytokine release and APC and effector T-lymphocyte activation, will likely improve prophylaxis of acute (and possibly chronic) GVHD. Therapy of established acute and chronic GVHD is still heavily dependent on corticosteroids, despite their limited efficacy and considerable toxicity. Novel agents (and/or combinations of agents) comprising pharmacologic, biologic and cellular therapies targeting specific steps or subsets involved in immune activation will likely comprise future advances in GVHD control. This article reviews the current state of knowledge regarding the prevention and treatment of acute and chronic GVHD. Novel approaches currently undergoing evaluation are also highlighted.

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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

Cited by 23 publications

References 8 publications

Pentostatin for treatment of steroid-refractory acute GVHD: a retrospective single-center analysis

Pentostatin for treatment of steroid-refractory acute GVHD: a retrospective single-center analysis

Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD

Current and future approaches for control of graft-versus-host disease

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