Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

Abstract

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.

New approaches in the diagnosis, pathophysiology, and treatment of pediatric hematopoietic stem cell transplantation-associated thrombotic microangiopathy

“…Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is caused by systemic vascular endothelial injury triggered by the transplantation process [1,2]. TMA affects multiple organs and occurs in about 30% of hematopoietic stem cell transplant (HSCT) recipients.…”

Thrombotic microangiopathy with concomitant GI aGVHD after allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

“…during the transplant process. [9][10][11] The risk factors for TA-TMA have been reported previously, including use of calcineurin inhibitors, an unrelated or mismatched donor, infection, and acute graft-vs-host disease (aGVHD). 1,[12][13][14][15] Acute graft-vs-host disease is another complication after allo-HSCT, which injuries a variety of organs, such as skin, liver, and gut.…”

Eculizumab for transplant‐associated thrombotic microangiopathy in adult allogeneic stem cell transplant recipients

“…20 Several factors have been identified to correlate with worse outcomes, including age ≥ 18 years old, unrelated donor, human leukocyte antigen (HLA)-mismatched donor, elevated TA-TMAI, schistocyte count > 5-10 per high-power field, renal dysfunction, neurologic impairment, concurrent veno-occlusive disease, elevated plasma concentrations of soluble terminal complement complex (sC5b-9), and proteinuria. 10,15,17,[20][21][22] Probable-TMA (ie, BMT-CTN criteria without renal or neurologic manifestations as defined by Cho, et al 10 ) and sirolimus (SRL)-induced TMA may suggest more favorable results. 10,[22][23][24] Various risk factors associated with the development of TA-TMA have been reported in the literature and are summarized in Table 2.…”

“…33 Therefore, other potential treatment options, including rituximab, defibrotide, and vincristine, have been explored. 20,28 Most recently, encouraging publications have emerged about the use of eculizumab (ECU) for the treatment of TA-TMA. Eculizumab is a terminal complement inhibitor approved by the US Food and Drug Administration (FDA) in 2007 for paroxysmal nocturnal hemoglobinuria (PNH) and in 2011 for aHUS.…”