Transplant-associated thrombotic microangiopathy (TA-TMA) is generally regarded as an early complication of hematopoietic stem-cell transplantation (HSCT); however, late TA-TMA appears to be nearly as common as early TA-TMA and both have similarly poor outcomes, according to findings published in the American Journal of Hematology.

In this retrospective study, the investigators aimed to characterize the risk factors and outcomes associated with early and late TA-TMA among patients receiving allogeneic HSCT. The researchers reviewed electronic medical records of adult patients who received allogeneic HSCT at the Mayo Clinic in Rochester, Minnesota, from January 2000 to June 2019. Patients were diagnosed with either early (before or on day 100 post-HSCT) or late (after day 100 post-HSCT) TA-TMA based on laboratory criteria.

Of 1451 HSCT recipients, 84 (5.8%) were diagnosed with TA-TMA at a median of 80 (range, 3-2595) days post-HCST: 45 patients (3.1%) were diagnosed with early TA-TMA at a median of 28 (range, 3-91) days and 39 patients (2.7%) were diagnosed with late TA-TMA at a median of 303 (range, 122-2595) days.

Of evaluated risk factors, patients with early TA-TMA were more likely to have calcineurin-inhibitor toxicity (66.7% vs 30.8%; P <0.001), acute graph-vs-host disease (GVHD; 66.7% vs 28.2%; P <.001), and prior HSCT (28.9% vs 5.1%; P =.005) compared with patients with late TA-TMA. Patients with late TA-TMA were more likely to have chronic GVHD during TMA than those with early TA-TMA (84.6% vs 0.0%; P <.001).


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The median follow up was 6 months (range, 0-132). The overall mortality rate was 34.5% at 3 months and 66.7% at the end of follow up. The estimated median overall survival (OS) was 6 months. After 1 year and 3 years, no differences were observed in survival of patients with early and late TA-TMA (1-year, 36.4% vs 48.9%; 3-year, 33.9% vs 32.9%, respectively). The estimated median OS was not reached in patients who had improvement of TA-TMA, whereas in patients with no improvement, it was 2 months (P <.001).

In a multivariate analysis, older age (for every 10 years, hazard ratio [HR], 1.40; 95% CI, 1.00-1.94; P =.049) and bacterial infection (HR, 2.42; 95% CI, 0.98-6.00; P =.056) were positively associated with mortality in the early TA-TMA group. Conversely, switching from calcineurin-inhibitor to mycophenolate mofetil treatment (HR, 0.40; 95% CI, 0.16-0.99; P =.047) and improvement of TMA (HR, 0.08; 95% CI, 0.03-0.25; P <.001) were negatively associated with mortality in the early TMA group. Only 1 independent predictor, improvement of TA-TMA, was associated with a lower risk of death in the late TMA group (HR, 0.05; 95% CI, 0.02-0.19; P <.001).

Limitations of the study included its retrospective design and variable patient management; additionally, some patients may have been undiagnosed or diagnosed later than the onset of TA-TMA.

“In conclusion, the characteristics and etiologies of early and late TMA may be different, but outcomes are similarly unfavorable. Future studies are needed to shed light on methods for a timely diagnosis, better definition of triggers of TMA, and to bring more targeted treatment options,” concluded the authors.

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Heybeli C, Sridharan M, Alkhateeb HB, et al. Characteristics of late transplant‐associated thrombotic microangiopahy (TA‐TMA) in patients who underwent allogeneic hematopoietic stem cell transplantation [published July 2, 2020]. Am J Hematol. doi: 10.1002/ajh.25922