Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

Abstract

Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults

“…[11][12][13] It remains a challenge to identify patients at highest risk for severe disease who may benefit from prompt clinical interventions. [14][15][16] Current diagnostic, prognostic, and therapeutic recommendations for HSCT-TMA are based on retrospective studies. [17][18][19] Therefore, we prospectively recruited children and young adults undergoing HSCT at our center to examine risk factors for the most severe TMA outcomes.…”

Remission of Microangiopathy in Transplanted Thalassemic Child

“…Some authors are in favour of complete stopping of medications such as CSA, Tacrolimus and Sirolimus as soon as TAM is diagnosed [3,4] but no reliable data have supported this suggestion [2]. Notably in our patient resumption of full dose CSA did not result in TAM relapse.…”

“…The incidence of TAM is variable, depending on the diagnostic difficulty, and varies 6-12 % after allogeneic transplantation and 1-5 % after autologous transplantation [3][4][5][6][7][8] with mortality rates as high as 30-50 %. Direct Coombs test was negative.…”

The potential role of HLA-DRB1*11 in the development and outcome of haematopoietic stem cell transplantation-associated thrombotic microangiopathy

“…1 Therefore, reported data show enormous variations in terms of incidence (0-75%), risks and mortality. [4][5][6]28 In a review of 35 reports from 2004, 28 different definitions were documented. 4 Attempts were made towards the harmonisation of the diagnosis and the application of the following three diagnostic criteria were suggested: Blood and Marrow Transplant Clinical Trials Network (2005), 26 International Working Group (2007) 29 and probable TMA (2010).…”