Zachary Paff

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

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.

Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT.

Patients undergoing auto-SCT for neuroblastoma present a unique population to study transplant-associated thrombotic microangiopathy (TA-TMA), due to standardized chemotherapy and later exposure to radiation and cis-retinoic acid (cis-RA). We retrospectively analyzed 20 patients after auto-SCT to evaluate early clinical indicators of TA-TMA. A total of 6 patients developing TA-TMA (30% prevalence) were compared with 14 controls. Four of six patients were diagnosed with TA-TMA by 25 days after auto-SCT. Compared with controls, TA-TMA patients had higher average systolic and diastolic blood pressure levels during high-dose chemotherapy and developed hypertension by day 13 after auto-SCT. Proteinuria was a significant marker for TA-TMA, whereas blood and platelet transfusion requirements were not. Serum creatinine did not differ between groups post transplant. However, patients with TA-TMA had a 60% decrease in renal function from baseline by nuclear glomerular filtration rate, compared with a 25% decrease in those without TA-TMA (P=0.001). There was no TA-TMA-related mortality. Significant complications included end-stage renal disease (n=1) and polyserositis (n=3). Patients with TA-TMA were unable to complete cis-RA therapy after auto-SCT. We suggest that careful attention to blood pressure and urinalysis will assist in the early diagnosis of TA-TMA, whereas serum creatinine seems to be an insensitive marker for this condition.

Abnormal Echocardiography 7 Days after Stem Cell Transplantation May Be an Early Indicator of Thrombotic Microangiopathy

Cardiac complications after hematopoietic stem cell transplantation (HSCT) can lead to significant morbidity and mortality. Cardiac evaluation during the first 100 days after HSCT is usually performed only if clinically indicated, and no studies have examined whether routine screening is beneficial in this patient population at high risk for tissue injury. We conducted a single-center prospective clinical study to screen for cardiac complications in pediatric and young adult patients. One hundred consecutive HSCT patients underwent scheduled echocardiographic screening on day +7 after transplantation, independent of their clinical condition. At least 1 abnormality was identified in 30% of cases. Seventeen children had a pericardial effusion, 13 elevated right ventricular pressure, and 3 reduced left ventricular function. Survival was reduced in children with any echocardiographic abnormality at day 7 (67% versus 80% in those with and without, respectively, abnormality, P = .073). Moreover, raised right ventricular pressure at day +7 was significantly associated with transplant-associated thrombotic microangiopathy (TA-TMA; P = .004) and may indicate early vascular injury in the lungs. These data suggest that echocardiography 7 days after HSCT can detect early cardiac complications of HSCT and may identify early vascular injury associated with TA-TMA.

Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients: Dandoy et al.

We observed pulmonary hypertension (PH), pericardial effusions, and left ventricular systolic dysfunction (LVSD) in multiple critically ill hematopoietic stem cell transplant (HSCT) recipients. We implemented routine structured echocardiography screening for HSCT recipients admitted to the pediatric intensive care unit (PICU) using a standardized multidisciplinary process.