hematology
Contributions
Type: Publication Only
Background
Thrombotic microangiopathy (TMA) is a rare but potentially devastating complication of allogeneic stem cell transplantation (allo-SCT). Its pathophysiology remains poorly understood. Mechanisms associated with TMA include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections or graft-versus-host-disease (GVHD). Management and treatment strategies of MAT remain challenging. Strategies as the discontinuation of calcineurin inhibitors or plasma exchange have limited efficacy. Eculizumab could be a promising complement targeting therapy for allo-SCT associated TMA.
Aims
To describe our experience with eculizumab in two cases of TA-TMA.
Methods
Post-allo-SCT TMA was diagnosed according to diagnostic criteria (International Working Group Definition for TMA (2007)). All patients received Tacrolimus (T) and Sirolimus (S) as immunosuppressive therapy. ADAMTS13 and serum C3 complement were analysed in all patients.
Results
2 patients with TA-MAT are described: Case 1: 53 year old woman diagnosed with refractory Hodgkin Lymphoma who underwent allo-SCT from a sibling donor. TA-TMA was diagnosed on day +34 post-allo-SCT. This patient had a severe kidney injury and neurologic disfunction and the blood tests confirmed an overdose of inmunosupressives. TMA treatment consisted in S and T withdrawal and plasma exchange with no response. ADAMTS13 was normal and serum C3 level was low. Induction therapy with 4 doses of Eculizumab was initiated with resolution of renal function and improvement of hemolysis parameters. Due to the excellent response we did not complete the maintenance treatment. Case 2: 52 year old woman diagnosed with AREB-II who underwent allo-SCT from a sibling donor. TMA was diagnosed on day +26 post-allo-SCT. This patient had a severe kidney injury, alveolar hemorrhage and the blood tests confirmed an overdose of inmunosupressives. ADAMTS13 and C3 were normal. The TMA treatment consisted in S and T withdrawal and plasma exchange with no response. Finally, induction therapy with Eculizumab was initiated. The patient received only 1 dose when normal C3 was confirmed and also because of the good evolution of renal function and hemolytic parameters.
Summary
Allo-SCT associated TMA is an uncommon but devastating complication of HCT. The pathogenesis is unclear. Although T and S have been implicated as risk factors for TA-TMA, there is no solid evidence supporting the discontinuation or dose reduction of these medications. Recently, it has been observed that both the classical and alternative complement pathways may be involved in TA-TMA, supporting the potential use of complement modulating therapies as Eculizumab in patients at highest risk for the worse outcomes. It poses certain challenges such as the reported difficulty of achieving therapeutic levels in critically ill HSCT patients, limited availability in certain countries and significant cost associated with this therapy. We achieved good response with the use of Eculizumab in one patient who had serum C3 low levels. Novel TMA biomarkers, reflecting predisposition for injury to specific organs, need to be identified in order to aid earlier TA-TMA.
Keyword(s): Allogeneic, Therapy, Thrombotic microangiopathy
Session topic: Publication Only
Type: Publication Only
Background
Thrombotic microangiopathy (TMA) is a rare but potentially devastating complication of allogeneic stem cell transplantation (allo-SCT). Its pathophysiology remains poorly understood. Mechanisms associated with TMA include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections or graft-versus-host-disease (GVHD). Management and treatment strategies of MAT remain challenging. Strategies as the discontinuation of calcineurin inhibitors or plasma exchange have limited efficacy. Eculizumab could be a promising complement targeting therapy for allo-SCT associated TMA.
Aims
To describe our experience with eculizumab in two cases of TA-TMA.
Methods
Post-allo-SCT TMA was diagnosed according to diagnostic criteria (International Working Group Definition for TMA (2007)). All patients received Tacrolimus (T) and Sirolimus (S) as immunosuppressive therapy. ADAMTS13 and serum C3 complement were analysed in all patients.
Results
2 patients with TA-MAT are described: Case 1: 53 year old woman diagnosed with refractory Hodgkin Lymphoma who underwent allo-SCT from a sibling donor. TA-TMA was diagnosed on day +34 post-allo-SCT. This patient had a severe kidney injury and neurologic disfunction and the blood tests confirmed an overdose of inmunosupressives. TMA treatment consisted in S and T withdrawal and plasma exchange with no response. ADAMTS13 was normal and serum C3 level was low. Induction therapy with 4 doses of Eculizumab was initiated with resolution of renal function and improvement of hemolysis parameters. Due to the excellent response we did not complete the maintenance treatment. Case 2: 52 year old woman diagnosed with AREB-II who underwent allo-SCT from a sibling donor. TMA was diagnosed on day +26 post-allo-SCT. This patient had a severe kidney injury, alveolar hemorrhage and the blood tests confirmed an overdose of inmunosupressives. ADAMTS13 and C3 were normal. The TMA treatment consisted in S and T withdrawal and plasma exchange with no response. Finally, induction therapy with Eculizumab was initiated. The patient received only 1 dose when normal C3 was confirmed and also because of the good evolution of renal function and hemolytic parameters.
Summary
Allo-SCT associated TMA is an uncommon but devastating complication of HCT. The pathogenesis is unclear. Although T and S have been implicated as risk factors for TA-TMA, there is no solid evidence supporting the discontinuation or dose reduction of these medications. Recently, it has been observed that both the classical and alternative complement pathways may be involved in TA-TMA, supporting the potential use of complement modulating therapies as Eculizumab in patients at highest risk for the worse outcomes. It poses certain challenges such as the reported difficulty of achieving therapeutic levels in critically ill HSCT patients, limited availability in certain countries and significant cost associated with this therapy. We achieved good response with the use of Eculizumab in one patient who had serum C3 low levels. Novel TMA biomarkers, reflecting predisposition for injury to specific organs, need to be identified in order to aid earlier TA-TMA.
Keyword(s): Allogeneic, Therapy, Thrombotic microangiopathy
Session topic: Publication Only