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

Abstract

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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“…Most of the patients received haploidentical stem cell transplantation. The conditional regimen for these patients was mainly a strategy of modified busulfan/cyclophosphamide and anti‐thymoglobulin (ATG), details were reported in our previously published articles 11–13 . The HLA‐matched recipients mostly received modified BU/CY regimen without ATG.…”

“…The source of hematopoietic stem cells was mostly peripheral blood stem cells and bone marrow stem cells, which were harvested in accordance with the protocol established by our institute 13 . GVHD prophylaxis strategy consists of short‐term MTX, mycophenolate and CsA 11,14 . Prophylaxis practices for GVHD and HZ remained consistent and comparable from 2012 to 2017.…”

“…13 GVHD prophylaxis strategy consists of short-term MTX, mycophenolate and CsA. 11,14 Prophylaxis practices for GVHD and HZ remained consistent and comparable from 2012 to 2017.…”

“…The conditional regimen for these patients was mainly a strategy of modified busulfan/cyclophosphamide and anti-thymoglobulin (ATG), details were reported in our previously published articles. [11][12][13] The HLA-matched recipients mostly received modified BU/CY regimen without ATG. A total body irradiation (TBI) based regimen was performed on patients who had a history of transplantation and other specific circumstances.…”

A systematic review of diagnostic, prognostic, and risk blood and urine biomarkers of transplant-associated thrombotic microangiopathy

“…Four studies reported prognostic implications of sC5b-9 including (1) values ≥ 244 ng/dl at the time of diagnosis ( 2 ); (2) a change in level of 1.8-fold from baseline to diagnosis ( 51 ); (3) an increase of a log at the time of TA-TMA ( 51 ); and (4) levels of sC5b-9 ≥300 ng/l and ANG-2 > 3000 pg/ml in patients with concurrent TA-TMA and GVHD ( 36 ). Markers of microangiopathy including decreased levels of haptoglobin ( 52 ), elevated levels of LDH ( 15 , 53 ), and scores that use laboratory values of microangiopathy, including BATAP (bilirubin, age, thrombocytopenia, anemia, proteinuria) ( 54 ) TMA index (LDH/platelets), and an EASIX score ( 55 ), all portended a poor prognosis. also portended a poor prognosis ( 14 ).…”