Abstract
Thrombotic microangiopathy (TMA) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT). The purpose of our study is to estimate the incidence, prevalence, and analyze the risk factors and outcome of TMA in children receiving HSCT. Patients under the age of 21 who underwent HSCT at one of the 42 Pediatric Health Information System (PHIS) hospitals from 2000–2012 were analyzed, including demographics, hospitalizations, TMA, and other HSCT-related complications. From 2000 to 2012, a total of 12,369 unique pediatric patients who received HSCT were identified. Among these, 93 (0.8%) children were identified to have the diagnosis of TMA. TMA was significantly associated with allogeneic HSCT, peripheral blood stem cell trasnplants (PBSCT), cytomegalovirus (CMV), human herpes virus 6 (HHV6), fungal infection, graft-versus-host disease (GVHD), and veno-occlusive disease (VOD) (p = 0.01). Multivariate logistic regression analysis of mortality showed only HHV6 was an independent risk factor associated with increased mortality in patients with TMA (hazard ratio: 2.86 [1.01, 8.39], p = 0.05). The prevalence of TMA in our study is 0.8% with a mortality in our pediatric TMA cohort of 30%, which is in contrast to the higher mortality reported in previously published, small-case series. HHV6 emerged as not only a risk factor for TMA but also as associated with increased mortality in these patients.
Highlights
Transplant-associated thrombotic microangiopathy (TA-Thrombotic microangiopathy (TMA)) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT)
While a few case studies of pediatric patients note that Transplant-associated thrombotic microangiopathy (TA-TMA) was preceded by a human herpes virus 6 (HHV6) infection, there is an ultimate lack of data regarding HHV6 association with TA-TMA [3,4]
The literature suggests a three-hit hypothesis, with the first hit being genetic factors, the second hit coming from conditioning regimens such as chemotherapy and/or radiation, and hit three occurring when the patient experiences other sources of endothelial injury, such as medication, graft-versushost disease (GVHD), or infection, such as with viral illnesses
Summary
Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT). As it is considered a part of the family of thrombotic endothelium disorders, the disease causes microangiopathic hemolytic anemia leading to microvascular thrombosis and fibrin deposition in the microvessels. Research shows that the disease is induced by endothelial cell injury, which could be the result of either infection, GVHD, chemotherapy, or radiation. We are currently working in the paradigm of a three-hit hypothesis, where patients with underlying genetic factors (Hit 1) that undergo conditioning regimens such as chemotherapy and/or radiation (Hit 2) and experience other potential sources of endothelial injury, such as infection, medication, or GVHD symptoms (Hit 3), are more likely to manifest the disease [2]. The purpose of our study is to estimate the incidence and prevalence of TA-TMA in children receiving HSCT and reveal other potential risk factors
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