Apheresis in grade 4 bone marrow transplant associated thrombotic microangiopathy: A case series

Abstract

Bone marrow transplant‐associated thrombotic microangiopathy (BMT‐TM) ranges in severity from a self‐limited to a fatal disorder. There has been no specific therapy for this condition. We have previously described a clinical grading system for BMT‐TM, based upon lactate dehydrogenase level (LDH) and percentage fragmented cells (FC) as follows: grade 0, normal or ↑ LDH and % FC ≤ 1.2%; grade 1, normal LDH and FC ≥ 1.3%; grade 2, ↑ LDH and FC = 1.3–4.8%; grade 3, ↑ LDH and FC = 4.9–9.6%; and grade 4, ↑ LDH and FC ≥ 9.7%. Patients with grade 4 BMT‐TM usually have fulminant disease and generally succumb. This study summarizes results using a variety of apheresis procedures in a series of 16 patients with grade 4 BMT‐TM. The apheresis procedures consisted of plasma exchange (with replacement with fresh frozen plasma or cryo‐poor plasma), and protein A immunoadsorption (PAI). The PAI exchanges were not done concurrently with plasma exchange procedures. Fifteen patients had undergone an allogeneic BMT and the 16th patient had undergone an autologous peripheral blood stem cell transplant. Half showed hematologic improvement with a downstaging of their TM to grades 1–3. All non‐responders died a median of 11 days following the onset of grade 4 BMT‐TM. The median survival in the responders was significantly (P = 0.001) increased to 218 days with three responders surviving more than 400 days following the onset of this severe complication. These results suggest a role for apheresis in the treatment of this lethal complication. Nevertheless grade 4 BMT‐TM represents a major complication of BMT; the median survival in this group of 16 patients with grade 4 BMT‐TM was only 31 days. © 1996 Wiley‐Liss, Inc.

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

“…11,12 Alternative predictors of response to PE have been reported by other authors, including TA-TMA index and LDH level. [13][14][15] Unlike these reports, we found no association between response to PE and grade of TA-TMA, TA-TMA index or LDH, but instead a significant association between response and presence or absence of active acute GVHD. Interestingly, resolution of TA-TMA in our patients with acute GVHD was seen only after subsequent control of GVHD through the alteration in immunosuppression.…”

“…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.…”

“…[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.…”

“…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.…”