Risk factors for transplant-associated thrombotic microangiopathy and mortality in a pediatric cohort

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is a well-recognized complication of hematopoietic cell transplantation (HCT). Diagnosis is challenging and in the absence of a tissue biopsy, TA-TMA is provisionally diagnosed by meeting clinical criteria. In this study, we describe the prevalence, outcomes, and risk factors for meeting 2 different diagnostic criteria for TA-TMA and for increased transplant-related mortality (TRM). In this retrospective study of 307 pediatric HCT patients, records were reviewed for the first 100 days after HCT. Patients who were diagnosed with TA-TMA by a provider during this time were included. In addition, the Cho et al criteria (2010) and Jodele et al (2014) TA-TMA criteria were applied retrospectively. Eight patients (2.6%) were diagnosed with TA-TMA by their provider. However, on retrospective review, 20% and 36% met the Cho and Jodele criteria for TA-TMA, respectively. Overall survival was significantly worse (P < .0001) and TRM was significantly higher in patients who met criteria for TA-TMA (MC-TA-TMA) (P < .0001). After controlling for comorbid conditions, MC-TA-TMA (hazard ratio [HR], 10.9; P = .0001) and grade 3/4 acute graft-versus-host-disease (aGVHD) (HR 3.5; P = .01) remained independently associated with increased TRM. Among allogeneic HCT recipients, features associated with an increased risk for MC-TA-TMA included ≥2 HCT, concurrent grade 3/4 aGVHD and concurrent infections. Among patients who MC-TA-TMA, LDH ≥2 times the upper limit of normal (P = .001), the need for ≥2 antihypertensive medications (P < .0001), and acute kidney injury (P = .003) were associated with significantly increased TRM.

Graphical abstract

Figure 1.

Overall survival, MC-TA-TMA vs no MC-TA-TMA by Cho and Jodele criteria. OS of patients MC-TA-TMA vs those not meeting Cho criteria (A) and Jodele criteria (B). OS was significantly worse in patients MC-TA-TMA using Cho criteria (A) or Jodele criteria (B) (P < .0001, log-rank test). Estimated survival at 100 days.

Figure 2.

Transplant related mortality, MC-TA-TMA vs no MC-TA-TMA by Cho and Jodele criteria. TRM of patients MC-TA-TMA vs those not MC-TA-TMA using Cho criteria (A) and Jodele criteria (B). TRM was significantly higher in patients MC-TA-TMA using Cho criteria or Jodele criteria vs those who did not meet criteria (P < .0001, Gray’s test).

Figure 3.

Risk stratification: characteristics associated with increased TRM in patients MC-TA-TMA. Among the 110 patients MC-TA-TMA, the factors associated with increased TRM included the need for >2 antihypertensive medications (P = .0001, Gray’s test) (A), LDH >2 times the ULN (P = .0011, Gray’s test) (B), and AKI (P = .0034, Gray’s test) (C).

Figure 4.

OS and TRM among allogeneic and autologous HCT reciepients, MC-TA-TMA vs no MC-TA-TMA. OS (A,C) and TRM (B,D) of allogeneic and autologous MC-TA-TMA among recipients of allogeneic HCT (n = 205). OS was significantly lower (A) (P < .0001, log-rank test) and TRM was significantly higher (B) (P < .0001, Gray’s test) in allogeneic recipients (n = 205) who met Jodele criteria for TA-TMA. (C) Among recipients of autologous HCT (n = 102), there was no significant difference in OS among patients MC-TA-TMA vs those who did not (P = .0704, log-rank test). (D) However, TRM was significantly higher in patients MC-TA-TMA (P < .0001, Gray’s test).