Transplant‐associated thrombotic microangiopathy: an unresolved complication of unrelated allogeneic transplant for hematologic diseases

Sakellari, Ioanna; Boussiou, Zoi; Batsis, Ioannis; Mallouri, Despina; Constantinou, Varnavas; Kaloyannidis, Kaloyannidis; Yannaki, Evangelia; Bamihas, Gerasimos; Anagnostopoulos, Achilles

doi:10.1002/hon.2346

Cited by 26 publications

(22 citation statements)

References 16 publications

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“…Except for pitfalls within the criteria, diverse patient populations and different diagnostic criteria are used among studies. Despite the wide range of TA‐TMA incidence described in the present literature (6%‐76%), our study is in line with previous studies by our group and others . Of note, TA‐TMA presented late post‐transplant (up to 721 days) in a number of our patients, suggesting that long‐term follow‐up is needed in all studies.…”

Section: Discussionsupporting

confidence: 91%

“…Classic hallmarks of the syndrome include microangiopathic hemolytic anemia in the absence of coagulopathy, hypertension accompanied by renal failure and central nervous system dysfunction such as seizure, stroke, or encephalopathy in a subset of patients. Cytopenias and organ dysfunction (especially kidneys, central nervous system, and liver) are relatively common after allogeneic HCT and may be initiated by drugs, infection, and graft‐vs‐host disease (GVHD), making recognition of TA‐TMA difficult . Since 2005, different consensus criteria have been proposed by the Blood and Marrow Transplants Clinical Trial Network (BMT‐CTN) and the International Working Group (IWG) and compared to one another .…”

Section: Introductionmentioning

confidence: 99%

“…Since 2005, different consensus criteria have been proposed by the Blood and Marrow Transplants Clinical Trial Network (BMT‐CTN) and the International Working Group (IWG) and compared to one another . However, their validation remains challenging in the absence of a gold standard for diagnosis, resulting to wide variations in estimates of incidence (6%‐76%) …”

Section: Introductionmentioning

confidence: 99%

“…Etiologic associations between TA‐TMA and calcineurin inhibitors, age, donor type, conditioning regimen, mTOR (mechanistic target of rapamycin) inhibitors, acute GVHD, and infections have been suggested . Although the role of clinical predictors in causing TA‐TMA remains unclear, further evaluation of clinical predictors in large cohorts may provide insight into earlier recognition of high‐risk patients and proper clinical management.…”

Section: Introductionmentioning

confidence: 99%

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Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Gavriilaki

Batsis

Mallouri

et al. 2018

Clinical Transplantation

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Renewed interest has emerged in transplant-associated thrombotic microangiopathy (TA-TMA) with novel prognostic, diagnostic, and treatment algorithms. We aimed to investigate the incidence, prognostic factors, morbidity, and mortality of TA-TMA in allogeneic hematopoietic cell transplantation (HCT) recipients. We enrolled consecutive HCT recipients (1990-2017). Among 758 patients, 116 (15.5%) were diagnosed with TA-TMA. In the multivariate analysis, TBI-based conditioning, viral infections, acute and chronic GVHD remained independent predictors of TA-TMA. With a median follow-up of 23 (range 0.1-329) months, TA-TMA resulted in significantly lower overall survival (OS). In the multivariate analysis, TA-TMA remained an independent predictor of OS, along with relapse, acute, and chronic GVHD. Among 116 TA-TMA patients, 70 developed renal (56) and/or neurologic (26) dysfunction that would be necessary for TA-TMA diagnosis according to the Bone Marrow Transplant Clinical Trials Network criteria. TA-TMA patients with renal dysfunction showed increased rates of acute GVHD, but no difference in OS compared to patients without renal dysfunction. However, neurologic dysfunction resulted in significantly lower OS. In conclusion, TA-TMA is associated with increased morbidity and mortality in allogeneic transplant recipients. Successful prevention and treatment strategies of infections and GVHD need to be timely employed to improve survival in this complex setting.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Gavriilaki

Batsis

Mallouri

et al. 2018

Clinical Transplantation

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“…1 TA-TMA diagnosis is often difficult and delayed since HCT recipients present with cytopenias and organ failure due to multiple triggers, including infections, graft-versus-host disease (GVHD) and toxicities. [2][3][4][5][6][7][8][9][10] In addition to difficulties in clinical presentation, current diagnostic criteria have been criticized for limited sensitivity, 11,12 highlighting that the cause of this clinical syndrome may be heterogeneous.…”

Section: Introductionmentioning

confidence: 99%

Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy

et al. 2020

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Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pretransplant genetic susceptibility is evident in adult TA-TMA and further investigated the association of TMA-associated variants with clinical outcomes. We studied 40 patients with TA-TMA, donors of 18 patients and 40 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pretransplant peripheral blood was sequenced for TMA-associated genes. Donors presented significantly lower frequency of rare variants and variants in exonic/splicing/untranslated region (UTR) regions, compared with TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13, CD46, CFH, and CFI. The majority of TA-TMA patients (31/40) presented with pathogenic or likely pathogenic variants. Patients refractory to conventional treatment (62%) and patients that succumbed to transplant-related mortality (65%) were significantly enriched for variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pretransplant genomic screening may be useful to intensify monitoring and early intervention in patients at high risk for TA-TMA.

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Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality

et al. 2019

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Transplant‐associated thrombotic microangiopathy: an unresolved complication of unrelated allogeneic transplant for hematologic diseases

Cited by 26 publications

References 16 publications

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Transplant‐associated thrombotic microangiopathy: Incidence, prognostic factors, morbidity, and mortality in allogeneic hematopoietic cell transplantation

Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy

Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality

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