Toward Improving Diagnostic Criteria for TA-TMA: Interim Analysis of A Multi-Center Retrospective Review By The TA-TMA Working Group

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2022

DOI

10.1038/s41409-022-01815-2

Journal Title

Bone Marrow Transplantation

Department

Pediatrics

Abstract

Background: Current diagnostic criteria for transplant-associated thrombotic microangiopathy (TA-TMA) were developed by expert panel or single-institution chart review and have not been rigorously validated or updated in several years. Several complications after hematopoietic cell transplantation (HCT) may share elements of these criteria, in part leading to considerable variability in the reported incidence of TA-TMA. The TA-TMA Working Group is conducting a multi-national, multi-center retrospective chart review to better estimate the occurrence of patients meeting defined criteria for TA-TMA, with the aim of using these data to inform consensus diagnostic criteria. The first stage of this study involved identifying appropriate screening criteria for TA-TMA. Methods: A total of 12 centers retrospectively screened patients who received allogeneic HCT (alloHCT) between 2015 and 2017. The following five criteria were used to screen for TA-TMA: schistocytosis (>2 per high-power field); LDH level above ULN; doubling of baseline creatinine; platelet refractoriness (50% decrease in platelet count and/or platelet count less than individual center's transfusion threshold × 4 days despite transfusions); and decreased haptoglobin. Patients were considered to have possible TA-TMA if they met ≥3 criteria within a 10- day period during the first 12 months post-HCT. Patients who had a positive biopsy, were diagnosed with TA-TMA or aHUS, or had received eculizumab following alloHCT were considered to have definite TA-TMA. Patients whose underlying hematologic disease relapsed before or within 1 month of screening positive for TATMA were excluded. Results: This interim analysis evaluated 2992 patients (total 2997 adult and pediatric cases) from 8 US and EU centers who underwent alloHCT during the study period. Patient characteristics are summarized in Table 1. There were no notable differences in HCT characteristics across study sites. Among all cases, 21.7% (range, 4.9-56.4%) met ≥3 criteria for TA-TMA; 5.6% were categorized as “unknown” due to missing data for TA-TMA criteria There was wide variability among the centers for number of patients screened for TA-TMA. Conclusions: Variability in identified potential cases across centers demonstrates the challenges associated with diagnosing TA-TMA. These preliminary results of patients meeting ≥3 criteria for TA-TMA provide data toward better defining diagnostic criteria; the next step is to adjudicate these cases and develop criteria for TA-TMA. The TATMA Working Group will ultimately develop guidelines and recommendations for the screening and diagnosis of TA-TMA.

This document is currently not available here.

Share

COinS