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Transplant-associated thrombotic microangiopathy may be ‘final pathway’ of other disorders
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ATLANTA — Transplant-associated thrombotic microangiopathy may be a final common pathway for several disorders with different pathophysiologic mechanisms, according to a retrospective cohort analysis presented at the ASH Annual Meeting and Exposition.
“It appears more than one condition is associated with the disease and it can be seen as a ‘common final pathway’ caused by many other complications,” Ang Li, MD, senior fellow of hematology and oncology at Fred Hutchinson Cancer Research Center at University of Washington and Seattle Cancer Care Alliance, told HemOnc Today.
Thrombotic microangiopathy is a clinical syndrome that can develop after hematopoietic cell transplantation. Previous studies limited to small case series have shown conflicting results.
“The study was necessary because transplant-associated thrombotic microangiopathy is a rare, but highly fatal, complication that can occur after a curative-intent bone marrow transplantation,” Li said.
Researchers used a large, single-center longitudinal database from 2006 through 2015 to describe the incidence, etiology, treatment and outcome of transplant-associated thrombotic microangiopathy — defined as persistent microangiopathic hemolytic anemia composed of red cell fragmentation, elevated lactate dehydrogenase, thrombocytopenia, anemia and lack of coagulopathy — among 2,241 consecutive adult allogeneic hematopoietic stem cell transplant recipients at Fred Hutchinson Cancer Research Center.
Of them, 209 patients (median age, 52; range, 40-60; 56% men; 85% white) experienced transplant-associated thrombotic microangiopathy after a median onset of 62 days (range, 35-93). One hundred nine patients experienced end-organ damage with either acute kidney injury or neurologic deficit.
Median follow-up was 181 days (range, 92-478), and 53 patients achieved hematologic resolution.
Acute graft-versus-host disease (n = 96) represented the largest category of pretransplant-associated thrombotic microangiopathy onset; those with GVHD refractory to high-dose steroids (n = 61) had poor prognosis.
Diffuse alveolar hemorrhage and idiopathic pneumonia syndrome (n = 30) frequently preceded thrombotic microangiopathy onset. Further, nonspecific causes of thrombotic microangiopathy included disease recurrence (n = 20) and systemic infection (n = 33).
“The reason this is important is that we have to know what we define as transplant-associated thrombotic microangiopathy before we can target and treat it,” Li said. “Rather than blindly following an algorithm — such as to stop all calcineurin inhibitors regardless of the cause — we need to look harder to see what may be the underlying triggers for this disease.”
Regardless of cause, the most common treatment was calcineurin inhibitor cessation or switch (32%). Researchers did not observe an association between changes to calcineurin inhibitor therapy and thrombotic microangiopathy resolution (24% vs. 26) or 6-month OS (37% vs. 34%). The achievement of thrombotic microangiopathy resolution was associated with significantly improved survival (HR = 0.35; P < .01).
“Future studies should involve standardization of definitions for this disease and discovery of biomarkers that can be used to diagnose this disease,” Li said. – by Chuck Gormley
Reference:
Li A, et al. Abstract 666. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Li reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.