Thrombotic microangiopathy with concomitant <scp>GI</scp> aGVHD after allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

Zhang, Xiaohui; Liu, Xiao; Wang, Qianming; He, Yun; Zhu, Xiaolu; Zhang, Jiamin; Han, Wei; Chen, Huan; Chen, Yuhong; Wang, Feng-Rong; Wang, Jing‐Zhi; Zhang, Yuanyuan; Mo, Xiao‐Dong; Chen, Yao; Wang, Yu; Fu, Hai-Xia; Chang, Ying‐Jun; Xu, Lei; Liu, Kai-Yan; Huang, Xiao‐Jun

doi:10.1111/ejh.12996

Cited by 11 publications

(7 citation statements)

References 60 publications

(144 reference statements)

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“…In our series, more than half of the patients who were diagnosed with TA-TMA with concomitant aGVHD died. This is also similar to previous reports from adults where Zhang et al 38 reported poor survival of 52% (n 5 50) among patients who developed TA-TMA vs 77% in patients who had only aGVHD (n 5 83) and 86.6% among patients who neither developed aGVHD nor TA-TMA and aGVHD (n 5 67) with higher nonrelapse mortality but low risk of relapse. Another group reported a drop in 90-day survival among patients with TA-TMA from 96% in patients with no documented driving factor to 50% in patients with concomitant GVHD.…”

Section: Discussionsupporting

confidence: 90%

“…Among the patient-derived risk factors, sex, and underlying disease did not influence the risk for TA-TMA, similar to data reported from previous studies. 16,35,38 On the contrary, others reported increased risk of TA-TMA among females more than males, whereas underlying disease had no impact. 21,39 In our cohort of patients, active comorbidity stood as a significant factor associated with TA-TMA.…”

Section: Discussionmentioning

confidence: 96%

“…A growing body of literature supports the role of endothelial dysfunction in the development of GVHD [53][54][55][56] with evidence of complement activation as a downstream effect of endothelial dysfunction. 57,58 Recent studies in adults showed a strong association between aGVHD grades III to IV and renal TA-TMA, 54 steroid refractory GVHD and TA-TMA, 58 and gastrointestinal aGVHD and TA-TMA 38 with dismal outcomes across most of the reports. In our series, more than half of the patients who were diagnosed with TA-TMA with concomitant aGVHD died.…”

Section: Discussionmentioning

confidence: 99%

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New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

Elfeky¹,

Lucchini

Lum

et al. 2020

Blood Advances

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This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation–based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

Elfeky¹,

Lucchini

Lum

et al. 2020

Blood Advances

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“…The gastrointestinal tract is frequently involved in a variety of posttransplant complications, with GVHD being one of the most common after allo-HSCT, and gastrointestinal tract involvement is seen in 74% of patients with aGVHD [45] and 30% of patients with cGVHD [46]. More than half of all patients with severe gastrointestinal GVHD are reported to experience GIB [47], and other complications, such as conditioning toxicity, infection and TMA, often affect the gut [48,49]. Thus, the causes resulting in the occurrence of GIB after HSCT vary, and the time of GIB onset is not always fixed.…”

Section: Discussionmentioning

confidence: 99%

Overt gastrointestinal bleeding following haploidentical haematopoietic stem cell transplantation: incidence, outcomes and predictive models

Sun

Xiao

et al. 2021

Bone Marrow Transplant

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“…Previous studies also reported adverse outcomes in TA-TMA patients with concomitant diffuse alveolar hemorrhage 11 and acute GVHD. 24 Considering the low response rate of current treatment strategies, 3,6 severe cases that require immediate intensification of support need to be identified at an earlier stage, ideally as soon as the diagnosis of TMA. However, most of the clinical risk factors were not readily applicable at the initial presentation of disease.…”

Section: Introductionmentioning

confidence: 99%

A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy

Zhao

et al. 2021

Blood Advances

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Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempt to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort according to the time of transplantation to perform external temporal validation. Patient age (OR 2.371, 95% CI 1.264-4.445), anemia (OR 2.836, 95% CI 1.566-5.138), severe thrombocytopenia (OR 3.871, 95% CI 2.156-6.950), elevated total bilirubin (OR 2.716, 95% CI 1.489-4.955) and proteinuria (OR 2.289, 95% CI 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was then constructed according to the regression coefficients. The validated c-statistics were 0.816 (95% CI 0.766-0.867) and 0.756 (95% CI 0.696-0.817) in the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.

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Thrombotic microangiopathy with concomitant GI aGVHD after allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

Abstract: Thrombotic microangiopathy with concomitant aGVHD is a significant complication after allo-HSCT, with a worse outcome, including significantly lower OS and higher NRM. There are specific risk factors associated with occurrence and mortality of this complication.

Cited by 11 publications

References 60 publications

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

Overt gastrointestinal bleeding following haploidentical haematopoietic stem cell transplantation: incidence, outcomes and predictive models

A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy

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