Emerging Concepts in Hematopoietic Stem Cell Transplantation–Associated Renal Thrombotic Microangiopathy and Prospects for New Treatments

Wanchoo, Rimda; Bayer, Ruthee-Lu; Bassil, Claude; Jhaveri, Kenar D.

doi:10.1053/j.ajkd.2018.06.013

Cited by 41 publications

(32 citation statements)

References 73 publications

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“…Although the available evidence is still fragmentary, a cumulative number of studies have shown that complement can be activated in types of TMA other than primary aHUS. 7 In secondary HUS, the activated procoagulant and proinflammatory endothelial cell phenotype characteristic of TMA can induce a nonspecific activation of complement, and different pathways of complement activation have been reported [8][9][10][11] ( Supplementary Table S1 and Supplementary References for Table S1). Serum samples from patients with both primary and secondary HUS induce C5b-9 deposition on cultured microvascular endothelium, and this deposition normalized after eculizumab treatment.…”

mentioning

confidence: 99%

Complement inhibitors are useful in secondary hemolytic uremic syndromes

Caravaca-Fontán

Praga

2019

Kidney International

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mentioning

confidence: 99%

Complement inhibitors are useful in secondary hemolytic uremic syndromes

Caravaca-Fontán

Praga

2019

Kidney International

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“…29,30 On the other hand, the evidence is gathering in support of the association between chronic GVHD with TMA. 17,18 One strong piece of evidence comes from the kidney where TMA is found along with other lesions associated with chronic GVHD lesions. 17,18 Interestingly, none of these patients were being treated with CNI at the time of the TMA.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 One strong piece of evidence comes from the kidney where TMA is found along with other lesions associated with chronic GVHD lesions. 17,18 Interestingly, none of these patients were being treated with CNI at the time of the TMA. This strongly supports chronic GVHD as a risk factor for late TA-TMA.…”

Section: Discussionmentioning

confidence: 99%

“…16 More recently, TMA has also been suspected to be associated with chronic GVHD, and some authors have proposed the TMA in the kidney as an endothelial version of GVHD. 17,18 Although GVHD typically affects epithelial surfaces, several reports have studied the endothelial effects of both acute and chronic GVHD. [19][20][21] Chronic GVHD typically occurs after day 100 of HSCT suggesting there could be late occurrence of TA-TMA.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of late transplant‐associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation

et al. 2020

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Transplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, 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. Switching to MMF 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 multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.

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“…An increasingly recognized complication of HSCT is HSCTassociated thrombotic microangiopathy (HSCT-TMA) [103], which has some features in common with betterknown microangiopathic processes such as thrombotic Patients can present to the ICU with acute kidney injury and neurologic changes in addition to hemolytic anemia and thrombocytopenia [65,104]. Management is predominantly supportive, with blood pressure control, cessation of any possible pharmacologic instigators (tacrolimus or cyclosporine), and renal replacement therapy playing major roles.…”

Section: Thrombotic Microangiopathymentioning

confidence: 99%

ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

Stephens

2020

Evidence-Based Critical Care

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A 44 year-old woman with a history of acute myeloid leukemia (AML) underwent a non-myeloablative haploidentical peripheral blood hematopoietic stem cell transplant (HSCT) 10 days ago. She was admitted to the hospital with fevers to 39 °C. On examination, she is anxious-appearing, with a temperature of 38.9 °C, a heart rate of 120 beats/min, a respiratory rate of 28 breaths/min, a blood pressure of 98/64 mmHg, and an oxygen saturation of 94% on 4 L/min oxygen via nasal cannula. A tunneled central venous catheter is in situ in her right internal jugular vein. Her total white blood cell (WBC) count is <0.5 cells/mm 3 and platelet count is 8000 cells/mm 3 . A chest CT scan shows diffuse patchy bilateral infiltrates (Figure). She is started on empiric antibiotic coverage with piperacillin/tazobactam, and 3 L of crystalloid are administered. Several hours later, she is more hypotensive, with nadir systolic pressures of 80-88 mmHg, and is more hypoxic, now saturating 85% on 6 L/min nasal cannula oxygen. QuestionHow should this patient be managed?Answer Broad spectrum antibiotics and lung-protective respiratory support.All patients after HSCT are immunosuppressed, profoundly so in the early post-transplant period before engraftment has occurred. This patient is likely to have a pneumonia with secondary septic shock, but a central line-associated infection from her tunneled central line is possible, as are non-infectious complications of HSCT. Respiratory failure is the most frequent cause of intensive care unit (ICU) admission after HSCT, most frequently from an infectious cause. The patient was placed on high-flow nasal cannula (HFNC) for oxygenation support and started on a norepinephrine infusion for hemodynamic support. Antibacterial coverage was changed to meropenem, levofloxacin, and vancomycin, and voriconazole was added for antifungal coverage. Her central line was removed. Her respiratory status continued to decline, and endotracheal intubation and mechanical ventilation were required 24 h after admission. She was placed on volume assist-control with a tidal volume of 6 mL/kg predicted body weight, and bronchoscopy with bronchoalveolar lavage (BAL) was performed. The BAL fluid was initially bloody, but cleared with sequential aliquots. Microbiologic studies of the BAL fluid were positive for respiratory syncytial virus and Pseudomonas aeruginosa. She was maintained on low tidal-volume ventilation and vasopressors were weaned off. Her white blood cell count slowly began to recover, and her respiratory status began to improve. She was extubated on hospital day 12 and was discharged from the ICU on hospital day 14. Principles of ManagementHematopoietic stem cell transplant (HSCT) has become an essential therapeutic modality in the treatment of malignant and non-malignant hematologic disease. In 2016, more than 23,000 HSCTs were performed in the United States, including approximately 15,000 autologous HSCTs and more than 8500 allogeneic transplants [1]. Allogeneic transplants are associated with more morbidity and m...

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Emerging Concepts in Hematopoietic Stem Cell Transplantation–Associated Renal Thrombotic Microangiopathy and Prospects for New Treatments

Cited by 41 publications

References 73 publications

Complement inhibitors are useful in secondary hemolytic uremic syndromes

Complement inhibitors are useful in secondary hemolytic uremic syndromes

Characteristics of late transplant‐associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation

ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

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