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Multicenter Study
. 2021 Jan 12;5(1):1-11.
doi: 10.1182/bloodadvances.2020003455.

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 , Sonata Jodele  1   2
Affiliations
Multicenter Study

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

Christopher E Dandoy et al. Blood Adv. .

Abstract

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 +100. 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.

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Conflict of interest statement

Conflict-of-interest disclosure: C.C.D. has acted as a consultant for Alexion, Inc. and Omeros Corporation. C.E.D. has received travel support and honoraria for lectures at European Society for Blood and Marrow Transplantation (EBMT) and American Society of Transplantation and Cellular Therapy (ASTCT) meetings from Omeros. P.R. has served as a member of the speaker;s bureau for Sobi. R.P. has served on the advisory board for Orchard Therapeutics. S.J. has US patent applications under review, is a lead Principal Investigator for a National Institutes of Health–funded multi-institutional study with drug provided by Alexion Pharmaceuticals, and has received travel support and honoraria for lectures at EBMT and ASTCT meetings from Omeros. S.M.D. has acted as a consultant for Novartis and has research support from Alexion Pharmaceuticals. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
TA-TMA screening and diagnosis algorithms for patients at participating centers. (A) Participating institutions implemented standardized screening for TA-TMA. (B) Diagnostic criteria for TA-TMA.
Figure 2.
Figure 2.
Cumulative incidence and 6-month survival in patients with and without TA-TMA. (A) Cumulative incidence of TA-TMA in all HSCT patients (N = 614). (B) Overall 6-month survival in allogeneic HSCT recipients with and without TA-TMA (n = 422). (C) Overall 6-month survival in autologous HSCT recipients with and without TMA (n = 192).
Figure 3.
Figure 3.
Cumulative incidence of TA-TMA in neuroblastoma patients according to pretransplant allocation (n = 72). Seventy-two patients underwent autologous HSCT for neuroblastoma; 21 (29%) were scheduled for single transplant and 51 (71%) were scheduled for tandem transplant. No patient developed TA-TMA from the single transplant cohort; 6 (29%) were diagnosed with VOD. No patients allocated to a single transplant had a delay in radiation, and 1 patient had a delay in antibody therapy (unknown reason). Thirteen (25%) of the patients who were scheduled to undergo a tandem transplant developed TA-TMA (1 after HSCT #1, 12 after HSCT #2), and 5 (10%) developed VOD. Three patients did not receive HSCT #2: 1 because of TA-TMA, 1 developed VOD, and 1 had disease relapse. Nine patients (18%) had a delay in receiving radiation (5 with TA-TMA, 2 with TA-TMA + VOD, 2 with VOD), and 9 patients (18%) had a delay in antibody therapy (7 with TA-TMA, 1 with TA-TMA + VOD, 1 with VOD). Bu, busulfan; CEM, carboplatin, etoposide, melphalan; Cy, cyclophosphamide; Mel, melphalan; Thio, thiotepa.
Figure 4.
Figure 4.
Outcomes of pediatric HSCT recipients with and without TA-TMA. CRRT, continuous RRT dialysis; ICU, intensive care unit.
Figure 5.
Figure 5.
Comparison of diagnostic and treatment variables and 6-month OS in patients diagnosed with TA-TMA (n = 98). (A) Six-month OS in patients diagnosed with TA-TMA who had proteinuria vs those who did not. (B) Six-month OS in patients who received any treatment vs those who did not. (C) Six-month OS in patients treated with eculizumab vs those who were not.
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References

    1. Barriga F, Ramírez P, Wietstruck A, Rojas N. Hematopoietic stem cell transplantation: clinical use and perspectives. Biol Res. 2012;45(3):307-316. - PubMed
    1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354(17):1813-1826. - PubMed
    1. Remberger M, Ackefors M, Berglund S, et al. . Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study. Biol Blood Marrow Transplant. 2011;17(11):1688-1697. - PubMed
    1. El-Bietar J, Warren M, Dandoy C, et al. . Histologic features of intestinal thrombotic microangiopathy in pediatric and young adult patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21(11):1994-2001. - PMC - PubMed
    1. Dandoy CE, Jodele S, Paff Z, et al. . Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2017;64(10):e26513. - PubMed

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