Transplant Associated-Thrombotic Microangiopathy (TA-TMA) In Pediatric Neuroblastoma (NB) Patients Undergoing Autologous Stem Cell Transplantation (ASCT): A Case-Control Study Identifying Early Clinical Markers Of Disease (2010)

Patients (pts) undergoing ASCT for NB present a unique population to study TA-TMA due to their standardized chemotherapy, lack of graft-versus host disease prophylaxis, and subsequent exposure to radiation and cis-retinoic acid (cisRA). We performed a retrospective case-control study of TA-TMA in NB pts who underwent ASCT at CCHMC in the past 5 years to identify strategies for early rigorous diagnosis. Twenty pts with high risk NB were treated with melphalan, carboplatin, and etoposide followed by ASCT. Six pts were diagnosed with TA-TMA (4 within 25 days of ASCT) presenting with microangiopathic hemolytic anemia, elevated lactate dehydrogenase, thrombocytopenia, hypertension (HTN), and acute kidney injury (3 confirmed with renal biopsy). Adenovirus, cytomegalovirus, and influenza B were potential triggers of TA-TMA (n=2). The 14 pts without TA-TMA served as controls. Clinical and laboratory data were obtained for the first 30 days pre- and post-ASCT. Blood pressure (BP) index was calculated as BP/95th percentiles for age and height (value >1=HTN). No pt had HTN pre-ASCT. Fischer's exact test, Wilcoxon rank sum and generalized linear models were used for analysis. Results are shown in the Table. Proteinuria, hematuria, and schistocytes on blood smear were significantly associated with TA-TMA, while blood and platelet transfusions were not. HTN requiring therapy proved to be a very significant indicator of TA-TMA and was identified within days of ASCT. Although serum creatinine (SCr) did not differ significantly between groups, pts with TA-TMA had an average 60% decrease in renal function from baseline by nuclear glomerular filtration rate (nucGFR) post ASCT, compared to a 30% decrease in those without TA-TMA. TA-TMA therapy included steroids, plasmapheresis, and rituximab. There was no TA-TMA-related mortality, but significant complications included progression to chronic dialysis (n=1) and severe polyserositis (n=2). None of the pts with TA-TMA were able to complete cisRA therapy. Overall, we found a 30% prevalence of TA-TMA in transplanted NB pts. The most significant indicator of TA-TMA was HTN. Our data are limited by their retrospective nature and small sample size. We suggest that careful BP observation and urinalysis monitoring will assist in the early diagnosis of TA-TMA, while SCr measurements are of limited value. Prospective studies are needed to confirm these results as early diagnosis and treatment may eventually help to improve outcome.Tabled 1Indicators of TA-TMA during first month post-ASCTVariableTA-TMA (n=6)No TA-TMA (n=14)P-valueProteinuria4 (67%)2 (15%)0.046Hematuria4 (67%)1 (8%)0.02Schistocytes4 (67%)1 (8%)0.02Pre-ASCT NucGFR152.0±12.9145.6±10.90.64Post-ASCT NucGFR∗61.0±8.8103.1±6.20.002SCr (mg/dL)0.54±0.040.49±0.020.28Systolic BP (mm Hg)112.2±2.5102.2±1.60.004Diastolic BP (mm Hg)66.7±2.255.4±1.50.001Systolic Index1.02±0.020.92±0.020.002Diastolic Index0.99±0.040.81±0.020.001Pts requiring HTN therapy5 (83%)3 (21%)0.006Data n (%) or mean ± standard error. ∗NucGFR (ml/min/1.73 m2) done on average 61 days post-ASCT Open table in a new tab Data n (%) or mean ± standard error. ∗NucGFR (ml/min/1.73 m2) done on average 61 days post-ASCT