Validation of Recently Proposed Consensus Criteria for Thrombotic Microangiopathy After Allogeneic Hematopoietic Stem-Cell Transplantation

Cho, Byung-Sik; Yahng, Seung‐Ah; Lee, Sung‐Eun; Eom, Ki‐Seong; Kim, Yoo-Jin; Kim, Heeje; Lee, Seok; Min, Chang‐Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong‐Wook; Min, Woo-Sung; Park, Chong-Won

doi:10.1097/tp.0b013e3181f24e8d

Cited by 249 publications

(260 citation statements)

References 21 publications

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“…1 The reported incidence of TA-TMA varies greatly from 0.5-63.6%, which is at least partly a consequence of the marked discrepancy in the definitions used and the lack of uniform criteria for diagnosis. 2 A generalized endothelial dysfunction, independent of ADAMTS-13 activity, appears to be the key event that represents the final common pathway of the disease, resulting in thrombosis and fibrin deposition in the microcirculation.…”

Section: Introductionmentioning

confidence: 99%

“…2 The exact pathophysiology of TA-TMA remains unclear, but a variety of potential risk factors have been suggested. 1,3,5,8,[10][11][12][13][14] The use of TAC plus SIR as GVHD prophylaxis has been associated with an increased incidence of TA-TMA, which ranges from 10.8-55%, the latter in patients who received BU plus CY as part of their conditioning regimen. [17][18][19]21,22 In a recent phase II multicenter prospective trial conducted by our group, including some of the patients in this study, no differences were observed in the incidence of TA-TMA when TAC/SIR was compared with patients included in a prior prospective trial using CYA-mycophenolate (the overall incidences of TA-TMA were 10% and 6%, respectively).…”

Section: Baseline Characteristics Of Patientsmentioning

confidence: 99%

“…[3][4][5][6] However, the exact pathophysiology of TA-TMA remains unclear. A variety of potential risk factors has been proposed, such as different conditioning regimens, [7][8][9][10][11] the development of acute GVHD, 1,3,8,[10][11][12][13][14] viral or fungal infections, 1,2 the use of unrelated donors, 11 HLA mismatch, 1 ABO incompatibility 10 and the use of calcineurin inhibitors (CYA and tacrolimus (TAC)) 15 or sirolimus (SIR) for GVHD prophylaxis. 16 The combination of TAC and SIR (TAC/SIR) in both solid organ transplantation and HSCT is associated with an increased risk of TA-TMA in some studies.…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Labrador

López-Corral

López‐Godino

et al. 2014

Bone Marrow Transplant

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Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n ¼ 68) or plus MTX (TAC/MTX) ± ATG (n ¼ 34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX ± ATG (7.4% vs 8.8%, P ¼ 0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC 425 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (Po0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.

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Section: Introductionmentioning

confidence: 99%

Section: Baseline Characteristics Of Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Labrador

López-Corral

López‐Godino

et al. 2014

Bone Marrow Transplant

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“…According to recent literature data [1,9] Due to non-availability of Defibrotide, a drug possibly effective in the treatment of TAM [10] and keeping in mind CMV reactivation and/or CSA as suspected causes of TAM we had no management option other than optimizing CMV treatment, decreasing CSA dose and introducing Mycophenolate mofetil for GVHD prophylaxis. These measures resulted in favourable outcome most probably because there was no associated GVHD.…”

Section: Discussionmentioning

confidence: 99%

Remission of Microangiopathy in Transplanted Thalassemic Child

Marwah

Soni

Faulkner³

et al. 2014

Indian J Hematol Blood Transfus

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Transplant associated thrombotic microangiopathy is a severe complication of Hematopoeitic stem cell transplantation. Although there is agreement in terms of diagnostic criteria, treatment options are not clarified yet. We present a patient aged 2.6 years who developed transplant associated thrombotic microangiopathy after allogeneic bone marrow transplantation and to discuss both risk factors and possible spontaneous remission of transplant associated thrombotic microangiopathy.

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“…Varying levels of awareness among institutions, diagnostic doubt and limited prospective data are reflected in the wide range of reported incidences of TA-TMA (from 0.5 to 76%). 64 TA-TMA is a member of the family of thrombotic microangiopathies, including, among others, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. 65 TA-TMA ensues when endothelial damage in the setting of HCT results in microangiopathic hemolytic anemia and platelet consumption, culminating in thrombosis and fibrin deposition in the microcirculation.…”

Section: Pathogenesismentioning

confidence: 99%

Acute kidney injury in HCT: an update

Lopes

Jorge

Neves

2016

Bone Marrow Transplant

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Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative hematopoietic cell transplantation (HCT); however, the pathogenesis and risk factors leading to AKI can differ between the two. The prognosis of AKI in patients receiving HCT is poor. In fact, AKI following HCT is associated not only with increased short-and long-term mortality, but also with progression to chronic kidney disease. Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis, as well as of the incidence, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and non-myeloablative regimens. INTRODUCTIONHematopoietic cell transplantation (HCT) is currently used to treat numerous malignant (for example, multiple myeloma, leukemias and lymphomas) and non-malignant hematological disorders (for example, aplastic anemia, b-thalassemia, immunodeficiency disorders and inborn errors of metabolism), as well as solid tumors (for example, breast cancer and neuroblastoma), which are in other instances incurable.The two major HCT procedures, taking into consideration the conditioning regimen used, are myeloablative autologous and allogeneic HCT and non-myeloablative allogeneic HCT. On the one hand, myeloablative HCT utilizes the maximally tolerated dose of TBI with or without chemotherapy, or with chemotherapy alone. On the other hand, non-myeloablative HCT depends more on donor cellular immune effects and less on the cytotoxic effects of the preparative regimen to control the underlying disease. 1,2 It ultimately uses a lower dose conditioning regimen and can thus be offered to older patients, to those debilitated by additional comorbidities, or to high-risk, heavily pretreated patients, who would not tolerate myeloablative HCT, resulting in a consequent decrease in regimen-related toxicity and treatment-related mortality. [3][4][5] Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative regimens; however, the pathogenesis and risk factors leading to AKI can differ between the two. In fact, AKI in patients receiving HCT is associated not only with increased short-and long-term mortality as compared with patients with no AKI, but also with a higher rate of progression to chronic kidney disease (CKD). Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis of AKI as well as of the incidence, risk factors, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and nonmyeloablative regimens.

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Validation of Recently Proposed Consensus Criteria for Thrombotic Microangiopathy After Allogeneic Hematopoietic Stem-Cell Transplantation

Abstract: Both proposed consensus criteria have major pitfalls in their use as uniformly accepted diagnostic criteria for TMA. The use of O-TMA as a broad definition for TMA and the grading system by the presence of renal involvement may be a counterproposal for future trials.

Cited by 249 publications

References 21 publications

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Remission of Microangiopathy in Transplanted Thalassemic Child

Acute kidney injury in HCT: an update

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