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

Abstract

• Proteinuria and elevated markers of complement activation at TMA diagnosis are associated with poor outcome.• Clinical interventions should be considered in HSCT patients with these high-risk features at the time TMA is diagnosed.Transplant-associated thrombotic microangiopathy (TMA) leads to generalized endothelial dysfunction that can progress to multiorgan injury, and severe cases are associated with poor outcomes after hematopoietic stem cell transplantation (HSCT). Identifying patients at highest risk for severe disease is challenging. We prospectively evaluated 100 consecutive HSCT recipients to determine the incidence of moderate and severe TMA and factors associated with poor overall outcomes. Thirty-nine subjects (39%) met previously published criteria for TMA. Subjects with TMA had a significantly higher nonrelapse mortality (43.6% vs 7.8%, P < .0001) at 1 year post-HSCT compared with those without TMA. Elevated lactate dehydrogenase, proteinuria on routine urinalysis, and hypertension were the earliest markers of TMA. Proteinuria (>30 mg/dL) and evidence of terminal complement activation (elevated sC5b-9) in the blood at the time of TMA diagnosis were associated with very poor survival (<20% at 1 year), whereas all TMA subjects without proteinuria and a normal sC5b-9 serum concentration survived (P < .01). Based on these prospective observations, we conclude that severe TMA occurred in 18% of HSCT recipients in our cohort and propose an algorithm to identify the highest-risk patients who might benefit from prompt clinical interventions. (Blood. 2014;124(4):645-653)

Eculizumab therapy in adults with allogeneic hematopoietic cell transplant-associated thrombotic microangiopathy

“…7,8,13,14 In the first prospective study of TMA in pediatric patients, incidence was reported to be as high as 35% and presence of TMA associated with higher non-relapse mortality than in patients without TMA. 1 Jodele et al 15 proposed that TMA is characterized by multi-organ endothelial injury affecting kidneys, gut, serosal surfaces, heart, skin and lungs, all in the setting of hemolytic anemia and thrombocytopenia. Martinez et al 16 studied 221 consecutive patients and noted a 31% incidence of TMA at 100 days post HCT.…”

“…[1][2][3] These conditions share a common end point of microthrombotic vascular endothelial cell injury, but with differing underlying pathophysiologic mechanisms. The TMA in TTP is related to severely deficient ADAMTS13 activity and the resulting ultra-large Von Willebrand factor multimers that aggregate platelets in conditions of high shear forces.…”

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

“…9,26 In 2014, an international panel suggested updated diagnostic guidelines. 1, 31 In our study, the adaptation of the proposed criteria was limited by the lack of serum complement C5b-9 measurements.…”

Post-bone marrow transplant thrombotic microangiopathy

“…The kidney is one of the most critical organs affected by this disease, emphasizing the importance of monitoring renal function via SCr or estimated glomerular filtration rate. Jodele et al 24 showed that in the early post-transplant phase, screening for proteinuria and monitoring urine protein/creatinine ratios can offer diagnostic and prognostic value for patients who are likely to develop TMA after transplantation. This study demonstrated the importance of close monitoring of urinary markers of kidney function, in addition to serum markers.…”