A pragmatic multi-institutional approach to understanding transplant-associated thrombotic microangiopathy after stem cell transplant

Christopher E. Dandoy,1,2 Seth Rotz,3 Priscila Badia Alonso,4 Anna Klunk,1,2 Catherine Desmond,1,2 John Huber,1,2 Hannah Ingraham,1,2
Christine Higham,5 Christopher C. Dvorak,5 Christine Duncan,6 Michelle Schoettler,6,7 Leslie Lehmann,6 Maria Cancio,8 James Killinger,8
Blachy Davila,9 Rachel Phelan,10 Kris M. Mahadeo,11 Sajad Khazal,11 Nahal Lalefar,12 Madhav Vissa,12 Kasiani Myers,1,2 Greg Wallace,1,2
Adam Nelson,1,2 Pooja Khandelwal,1,2 Deepika Bhatla,13 Nicholas Gloude,14 Eric Anderson,14 Jeffrey Huo,15 Philip Roehrs,15
Jeffery J. Auletta,16,17 Ranjit Chima,2,18 Adam Lane,1,2,19 Stella M. Davies,1,2 and Sonata Jodele1,2

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of
hematopoietic stem cell transplantation (HSCT). A single-center prospective screening study
has shown that the incidence of TA-TMA is much higher than prior retrospective studies that
did not systematically screen. These data have not been replicated in a multicenter study.
Our objective was to determine the incidence and risk factors for TA-TMA and compare
outcomes of pediatric HSCT patients with and without TA-TMA. Patients were prospectively
screened for TA-TMA at participating centers using a simple to implement and inexpensive
strategy from the start of the preparative regimen through day 1100. TA-TMA was
diagnosed if $4 of 7 laboratory/clinical markers diagnostic for TA-TMA were present
concurrently or if tissue histology showed TA-TMA. A total of 614 patients (359 males; 58%)
received prospective TA-TMA screening at 13 pediatric centers. TA-TMA was diagnosed in 98
patients (16%) at a median of 22 days (interquartile range, 14-44) posttransplant. Patients
with TA-TMA had significantly increased bloodstream infections (38% [37/98] vs 21%
[107/51], P # .001), mean total hospitalization days (68; 95% confidence interval [CI], 63-74 vs
43; 95% CI, 41-45; P # .001), and number of days spent in the intensive care unit (10.1; 95%
CI, 6.4-14; vs 1.6; 95% CI, 1.1-2.2; P # .001) in the first 100 days after HSCT compared with
patients without TA-TMA. Overall survival was significantly higher in patients without
TA-TMA (93%; 490/516) compared with patients with TA-TMA (78%; 76/98) (P # .001). These
data support the need for systematic screening for TA-TMA and demonstrate the feasibility
and efficacy of an easy to implement strategy to do so.