Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease

Abstract

Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week, discontinuation of the CI and continuation of the remaining GVHD treatment. All patients had acute GVHD (steroid-sensitive (n ¼ 4), steroid-refractory (n ¼ 10)) or chronic GVHD (n ¼ 4) and were treated with CI before the start of daclizumab. Nine of 13 patients with TAM treated with daclizumab and discontinuation of CI achieved complete remission of TAM, two had stable disease, and one patient did not respond. Patients receiving daclizumab for RI without TAM showed stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients with acute GVHD achieved CR, two partial remission, eight patients did not respond and 11/14 died at a median of 39 days after start of the daclizumab. Our data demonstrate that replacement of CI by daclizumab can improve TAM and RI. However, mortality remains high in patients with acute GVHD.

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

“…10,18,40-42 Case series have indicated a possible role of daclizumab, 43 defibrotide, 44 and vincristine. 45,46 More recently, eculizumab has been utilized to manage these patients 13 based on its efficacy in aHUS.…”

“…56 Interleukin 2 receptor antagonists such as basiliximab and daclizumab have also shown benefit in a few patients with TA-TMA. 40,43 In an Italian study of 12 patients, the early use of defibrotide resulted in a response rate of 50%. 44 Plasma exchange has been used for several decades to treat TMA including TA-TMA.…”

Onco-Nephrology

“…Other oral agents that can be used for the prevention and treatment of GVHD include mycophenolate mofetil and corticosteroids (65). Substitution of calcineurin inhibitors with daclizumab, a humanized monoclonal antibody to the a-chain of the IL-2 receptor, has been shown to improve TMA in patients with both GVHD and TMA (66). Rituximab, a monoclonal antibody against CD20, and defibrotide have also shown effectiveness in treating HCT-associated TMA in small, uncontrolled studies (67).…”

Remission of Microangiopathy in Transplanted Thalassemic Child

“…Some centres employed plasma exchange as part of the management of TAM but response rate has been disappointing in this setting [10] while favourable results have been shown in idiopathic Microangiopathy only [10,11].…”