Incidence, Risk Association and Outcomes of Adult Transplant Associated Thrombotic Microangiopathy By Applying Modified Jodele Criteria - a Single Center Experience

Introduction:

Transplant associated thrombotic microangiopathy (TA-TMA) is a well-recognized complication of allogeneic hematopoietic stem cell transplantation (HSCT) with the highest incidence being in the first hundred days after transplant. Incidence of and risk factors associated with TA-TMA are poorly studied due to previous lack of a clear definition of the condition. Following publication of the recent consensus paper (American Society for Transplantation and Cellular Therapy, European Society for Blood and Marrow Transplantation, Asia-Pacific Blood and Marrow Transplantation Group and Center for International Blood and Marrow Transplant Research) on defining criteria for TA-TMA, proposed as the modified Jodele criteria, we studied the incidence, risk factors and outcomes of this condition.

Objectives:

To define the incidence of TA-TMA in adult allogeneic HSCT patients at our institution in the first 100 days after transplant, using the modified Jodele criteria.

To define the incidence of high versus standard risk TA-TMA in adult allogeneic HSCT patients.

To assess risk factors associated with the development of TA-TMA.

Methods:

Retrospective chart review of all adult patients who underwent allogeneic HSCT between 4/2021 and 12/2023 at our institution.

Results:

During this period, 525 allogeneic HSCTs were performed at our institution, 92 (17.5%) of whom developed TA-TMA as defined by modified Jodele criteria, in the first 100 days after transplant.

In the TA-TMA cohort, 54.4% were male. The median age at diagnosis was 63 years. 89.13%, 9.8% and 1.1% patients underwent peripheral blood SCT, cord blood SCT and bone marrow SCT, respectively.

Of the risk factors assessed, the combination of a calcineurin inhibitor and mTor inhibitor (Rapamycin) for immune suppression was found to be a significant risk (OR 1.8456 (95% CI: 1.1670 to 2.9474, P=0.0090). The use of post-transplant Cytoxan for graft-versus-host-disease prophylaxis was not found to be a significant risk (OR 1.54 CI 0.9723 to 2.4393 P=0.0658). Conditioning regimen comprising of Melphalan, Fludarabine and TBI was also noted to be a significant risk factor (OR 2.4630 (95% CI: 1.4015 TO 4.3284, p=0.0017). Of the indications for transplant, MDS was noted to be a significant risk with an odds ratio of 6.1667 (95% CI: 3.3755 to 11.2659 P=< 0.0001).

Of the 92 patients who met criteria for TA-TMA, 83 (90%) met criteria for high-risk TA-TMA.

6-month post-transplant mortality in the TA-TMA cohort was noted to be 26% versus 7% in the non-TA-TMA cohort.

Conclusions:

The incidence of TA-TMA in adults in the first hundred days after allogeneic HSCT is significant and is associated with a high mortality rate. Immune suppression with calcineurin inhibitor-m-tor combination, melphalan-fludarabine -TBI conditioning are potential risk factors for the development of TA-TMA. However, concurrent GVHD and infections are likely to contribute significantly to the development of TA-TMA, and their role must be further defined by multivariate analyses.

A large percentage of patients with TA-TMA (90) meet criteria for high-risk TA-TMA.

Prospective studies will inform additional risk factors, and the role of disease directed therapy in high-risk TA-TMA.

Panch:Sanofi: Consultancy; Sobi: Consultancy.