15-Deoxyspergualin “Rescue Therapy” for Methylprednisolone-Resistant Rejection of Renal Transplants as Compared With Anti-T Cell Monoclonal Antibody (Okt3)

Okubo, Mitsuo; Tamura, Kentaro; Kamata, Kenji; Tsukamoto, Yumiko; Nakayama, Yuko; Osakabe, T; Sato, Kimitaka; Go, Mitsuru; Kumano, Kotaro; Endo, Tadao

doi:10.1097/00007890-199303000-00010

Cited by 25 publications

(14 citation statements)

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“…In clinical trials including patients with recurrent kidney transplant rejections, DSG led to remission in 79% of cases (11). Moreover, in a randomized trial in patients with steroid-resistant kidney transplant rejections, DSG was as effective as the monoclonal antibody OKT3, showing reversal of acute rejection in 59% respectively 62% (12). Recently, Hotta et al (13) demonstrated that DSG shows therapeutic efficacy in patients with crescentic proliferative glomerulonephritis.…”

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confidence: 99%

“…Recently, Hotta et al (13) demonstrated that DSG shows therapeutic efficacy in patients with crescentic proliferative glomerulonephritis. From preclinical and clinical data, DSG appears to be a potent immunosuppressant with a favorable side effect profile exerting no renal, liver, or diabetogenic toxicity and only reversible bone marrow suppression (11)(12)(13)(14). To assess the efficacy and tolerability of DSG, we conducted a pilot trial in patients with active WG or MPA refractory or with contraindications to standard immunosuppressants.…”

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confidence: 99%

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15-Deoxyspergualin in Patients with Refractory ANCA-Associated Systemic Vasculitis

Birck

Warnatz²,

Lorenz

et al. 2003

Journal of the American Society of Nephrology

139

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ABSTRACT. The combination of cyclophosphamide (CYC) and oral corticosteroids is effective in the majority of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AASV), but it carries substantial risk of drug-related morbidity and mortality. New regimens are desired, especially in refractory cases. The immunosuppressant 15-deoxyspergualin (DSG) is effective in experimental autoimmune disease and transplantation as well as in acute kidney transplant rejection in humans. To assess the efficacy and safety of DSG, an open label multicenter trial was conducted in patients with AASV who were either unresponsive or had contraindications for standard immunosuppressants. Included were 19 cases of Wegener granulomatosis and one case of microscopic polyangiitis. Nine of them had received CYC shortly before study entry without apparent therapeutic success. DSG (0.5 mg/kg per d) was given for 2 to 3 wk until the WBC count dropped to 3000/μl followed by a rest until at least a WBC of 4000/μl was reached again. This was repeated up to six cycles. During the study, no other immunosuppressants besides steroids were allowed. Disease improvement during treatment with DSG was achieved in 70% of cases (six cases of complete remission; eight cases of partial remission). Leucopenia occurred in each patient in a regular pattern during the cycles and was transient without exception. No mortality or septicemia was observed. Mild to moderate infections mainly in the respiratory tract were observed but resolved under adequate treatment without sequel. It is concluded that treatment with DSG is successful in patients with refractory Wegener granulomatosis under careful monitoring of WBC count. E-mail: rainer.birck@med5.ma.uni-heidelberg.de

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confidence: 99%

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confidence: 99%

15-Deoxyspergualin in Patients with Refractory ANCA-Associated Systemic Vasculitis

Birck

Warnatz²,

Lorenz

et al. 2003

Journal of the American Society of Nephrology

139

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“…Particularly, in the case of rescue therapy for acute rejection after kidney transplantation, it was reported that therapy using DSG combined with MP was onehundred percent effective while DSG alone was effective in more than 70% of the cases (Kenmochi et al 1990). Moreover, it was reported that the efficacy of DSG and that of OKT3 against steroid resistant acute rejection were comparable (Ohkubo 1993).…”

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confidence: 97%

“…The results of phase I and phase II clinical trials showed that DSG was useful in several situations: (i) prophylaxis and treatment of acute rejection, (ii) prevention of antibody response to biologic agents used for immunosuppression, (iii) suppression of the humoral response at the time of transplantation in sensitized patients, and (iv) inhibition of macrophage-mediated damage of cellular transplantation (e.g., islets) (Wahoff et al 1996). In a randomized study of DSG vs anti-CD3 monoclonal antibody (OKT3) for the treatment of steroidresistant acute rejection in renal transplantation, no significant difference in efficacy was found between the two groups (Ohkubo et al 1993). However, the side effects profile of DSG was significantly better than that of OKT3 (Ohkubo et al 1993).…”

confidence: 99%

“…In a randomized study of DSG vs anti-CD3 monoclonal antibody (OKT3) for the treatment of steroidresistant acute rejection in renal transplantation, no significant difference in efficacy was found between the two groups (Ohkubo et al 1993). However, the side effects profile of DSG was significantly better than that of OKT3 (Ohkubo et al 1993).…”

confidence: 99%

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Usage of Deoxyspergualin on Steroid-Resistant Acute Rejection in Living Donor Liver Transplantation

Kawagishi

Satoh

Enomoto

et al. 2006

Tohoku J. Exp. Med.

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Polyclonal and monoclonal antibodies for treating acute rejection episodes in kidney transplant recipients

Webster

Tallapragada

et al. 2017

Cochrane Database of Systematic Reviews

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In reversing first acute cellular rejection and preventing graft loss, any antibody is probably better than steroid, but there is little or no difference in subsequent rejection and patient survival. In reversing steroid-resistant rejection there was little or no difference between different antibodies over a period of 12 months, with limited data beyond that time frame. In treating acute humoral rejection, there was no evidence that the use of antibody therapy conferred additional benefit in terms of reversal of rejection, or death or graft loss.Although this is an updated review, the majority of newer included studies provide additional evidence from the cyclosporin/azathioprine era of kidney transplantation and therefore conclusions cannot necessarily be extrapolated to patients treated with more contemporary immunosuppressive regimens which include tacrolimus/mycophenolate or sirolimus. However, many kidney transplant centres around the world continue to use older immunosuppressive regimes and the findings of this review remain strongly relevant to their clinical practice.Larger studies with standardised reproducible outcome criteria are needed to investigate the outcomes and risks of antibody treatments for acute rejection in kidney transplant recipients receiving contemporary immunosuppressive regimes.

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15-Deoxyspergualin “Rescue Therapy” for Methylprednisolone-Resistant Rejection of Renal Transplants as Compared With Anti-T Cell Monoclonal Antibody (Okt3)

Cited by 25 publications

References 0 publications

15-Deoxyspergualin in Patients with Refractory ANCA-Associated Systemic Vasculitis

15-Deoxyspergualin in Patients with Refractory ANCA-Associated Systemic Vasculitis

Usage of Deoxyspergualin on Steroid-Resistant Acute Rejection in Living Donor Liver Transplantation

Polyclonal and monoclonal antibodies for treating acute rejection episodes in kidney transplant recipients

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