Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants

Abstract

Summary:We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27718% for TAM with high schistocyte counts; 53715% for TAM with low schistocyte counts; vs 7877% in patients without TAM; Po0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.

Transplantation-associated thrombotic microangiopathy: effect of concomitant GVHD on efficacy of therapeutic plasma exchange

“…Our findings are in concordance with previous publications of use of PE in TA-TMA, in which significant response rates to PE have been reported. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Of note, all patients in our series had multifactorial fulminant TA-TMA, a subgroup of TA-TMA initially reported to be unresponsive to PE. 4,10 However, subsequent experience suggested that mild Grades (0-2) of multifactorial fulminant TA-TMA may indeed respond to PE.…”

“…However, recent publications have suggested that PE has limited efficacy in treatment of TA-TMA, with relatively low response rates (20-50%) in comparison to idiopathic TTP (75%) generally reported. 2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] This overall poor response to PE in TA-TMA is not necessarily surprising in light of recent insights into its pathogenesis, which suggest that TA-TMA is, in fact, a multifactorial disorder resulting from endothelial cell dysfunction secondary to a variety of insults, including immunosuppressive medications, GVHD and (especially viral) infection. 2,3,8 Unlike idiopathic TTP, TA-TMA has only rarely been associated with severe deficiency of the plasma protease ADAMTS13.…”

“…2,3,24 However, this belies the fact that significant clinical responses have been reported in a significant minority of patients treated with PE in a majority of published TA-TMA series to date. [1][2][3][4][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Owing to this historic experience, in many transplant centres, including our own, PE continues to be used in the management of TA-TMA. In an attempt to determine which clinical factors may be predictive of response (or lack thereof) to PE, we retrospectively reviewed the outcomes of TA-TMA treated with therapeutic PE at our institution.…”

“…[1][2][3][4][5][6][7] This uncertainty in diagnosis has led to wide variations in the reported incidence of TA-TMA, a lack of consensus regarding clinical approach to management, and poor understanding of prognostic factors with respect to therapeutic response and survival. [1][2][3][4][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] To address this issue of diagnostic clinical uncertainty, two new diagnostic criteria for TA-TMA have recently been proposed; the Bone Marrow Transplant Clinical Trials Network (BMT-CTN) and the IWG (International Working Group) TA-TMA criteria. 24,25 However, neither criterion has been rigorously evaluated clinically, and issues remain with respect to the diagnostic sensitivity of both.…”

The Use of Hyperbaric Oxygen Therapy in the Treatment of Non-healing Ulcers Secondary to Graft-versus-host Disease

“…1 While there appears to be a well-established role of bone marrow transplant (BMT), GvHD and its treatment in the development of thrombotic micro-angiopathy include varied states of hemostatic abnormality with clinical comparison to thrombotic thrombocytopenia purpura. 3 Despite a few transient episodes of elevated LDH, there was no such histopathologic or clinical history that would suggest such a relationship in this patient. That said, more recent review of the literature describes instances of less specific forms of micro-angiopathy and endothelial damage in the course GvHD leading to ischemia and fibrosis.…”