The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation

Abstract

Summary. In this study, we retrospectively analysed the clinical features, risk factors and outcome of 22 patients with thrombotic thrombocytopenic purpura (TTP) occurring after allogeneic stem cell transplantation. All but two of these patients received stem cells from unrelated donors (UDs), two-thirds were female, three-quarters were adults and leukaemia was the major reason for transplant. The incidence of TTP was 20 out of 332 patients (6%) with UD transplants and two out of 104 recipients (2%) of matched sibling allografts (P 0´16). In order to ascertain basic demographic risk factors for the development of TTP, we compared the 22 patients with 434 patients who did not develop TTP. Compared with patients who did not develop TTP, patients with TTP were nearly three times older (P , 0´001) and were more than twice as likely to be female (P 0´001). Because . 90% of patients were recipients of UD marrow, we then compared the 20 UDbone marrow transplantation (BMT) patients with 60 randomly selected UD-BMT patients who did not develop TTP. On univariate analysis, age and female gender were again significant risk factors, as was grade II±IV acute graft-versus-host disease (GvHD) (P 0´002), and there was a trend towards an association with chronic GvHD (P 0´083). However, after logistic regression analysis, only age and sex remained significant (P , 0´001 and 0´009 respectively). We report an 86% mortality with only three survivors out of 22 patients, and one of these remains thrombocytopenic and red cell transfusion dependent, possibly in part because of graft hypoplasia. Six out of 17 patients responded to plasmapheresis, but the majority of them ultimately succumbed because of TTP, often in association with GvHD or fungal infection.

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

“…33 The higher risk of TAM observed among female patients has also been observed in other studies. 6,11,12,16 This present study confirms this gender effect but the pathophysiology remains unresolved, hypotheses include a role of hormones, oral contraceptives, sensitization by pregnancy or other hitherto unknown factors. The increased risk for TAM was only observed with female patients, whereas stem cell transplants from female donors were not associated with a higher risk for TAM suggesting that it is not an effect of the donor stem cells, but rather of the host environment.…”

“…16 We did not find more TAM in recent years nor with use of peripheral stem cells. Peripheral stem cells have been shown to be associated with more chronic but not with more aGvHD, and TAM is generally an early event after HSCT.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Thrombotic microangiopathy is characterized by systemic or intrarenal platelet aggregation and a microangiopathic hemolytic anemia, with red blood cell (RBC) fragmentation and a negative direct antiglobulin test. Increased platelet consumption leads to thrombocytopenia.…”

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

“…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.…”

“…[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.…”