Outcomes and Clinical Characteristics of Adult Patients with Transplant Associated Thrombotic Microangiopathy: A Single Center Experience

Background:

Transplant Associated Thrombotic Microangiopathy (TA-TMA) represents a significant cause of Non-Relapse Mortality (NRM) in patients undergoing Allogeneic Stem Cell Transplantation (SCT). While this complication has been well documented in the pediatric population, it remains underrecognized in the adult population.

Methods:

We conducted a retrospective study evaluating outcomes of consecutive adult patients (>18 y) undergoing SCT at O'Neal Comprehensive Cancer Center at UAB during 2019 and 2020 calendar years for any indication and including any conditioning regimen intensity. The likelihood of TA-TMA was adjudicated after retrospective chart review by investigators, using the recently published harmonization panel consensus criteria for diagnosis (Schoettler et al. TCT 2023). Relapsed patients were excluded from analysis.

Results:

85 consecutive patients were identified, 22 patients were excluded due to relapse, leaving 63 patients for primary analysis. Median age was 60 years old (range 22-74) , median BMI was 30.7 (range 19.74 - 45.71) and median HCT-CI score was 3 (range 0-8), 74.60% (47/63) patients were Non-Hispanic White (NHW), with the rest being African American (AA), 66.7% (42/63) were male and 95.2% (60/63) had a malignant indication, 55.6% patients received transplants from Matched Unrelated Donor (MUD), 15.9% from Matched Related Donor (MRD) 22.2% from Haploidentical (H) and 6.3% from Mismatched Unrelated Donor (mMUD), 76.2% of patients received reduced intensity or non-myeloablative (RIC/NMA) conditioning regimen. The rate of Grade II-IV aGVHD was 35% and of moderate-severe cGVHD was 33.3%. 30.2% (19) of patients met criteria for TA-TMA, 68.4% (13/19) were noted to have developed TA-TMA in the setting of either infection (7) or GVHD (6). Most common intervention was to either decrease immunosuppression or transition to another immunosuppressive agent (63.1%, 12/19), however, only in 2 patients was this done under clinical suspicion of TA-TMA. No patients received eculizumab or other complement inhibition. Median follow-up time was 45.3 months. AA ethnicity (p=0.045), use of TBI (p=0.033), development of post-SCT viral infection (p=0.01), use of renal replacement therapy after SCT (p=0.011), higher pre transplant serum creatinine (p=0.004) and platelet and red blood cell transfusion dependence (p<0.0001) were all associated with development of TA-TMA. Patients who developed TA-TMA had lower OS (23.34 vs 54.54 months, p<0.0001), however, no difference in OS was observed between AA and NHW patients (42.92 vs 45.83 months, p=0.87)

Conclusions:

TA-TMA represents an underrecognized source of morbidity and mortality among adult patients undergoing SCT, factors such as AA ethnicity, TBI use, post SCT viral infection, renal dysfunction and development of transfusion dependence were all associated with development of TA-TMA. Prospective evaluation of risk factors for TA-TMA and therapeutic strategies are highly needed. These findings have led to the development of TA-TMA screening guidelines for our institution.

Vasu:Alexion Inc: Other: Advisory Board; Lentigen/Miltenyi Biotec: Research Funding; Sanofi Inc: Research Funding.