Thrombotic thrombocytopenic purpura after allogeneic hematopoietic cell transplantation: A rare but fatal complication.

Abstract Introduction Thrombotic microangiopathy (TMA) is a common and potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The underlying mechanisms of TMA after transplantation can be diverse, but current knowledge regarding TMA after allo-HSCT has focused on transplant-associated thrombotic microangiopathy (TA-TMA), which is typically caused by abnormalities in the complement pathway. However, thrombotic thrombocytopenic purpura (TTP), another kind of TMA caused by severe ADAMTS13 deficiency, is rarely mentioned. According to the latest guideline, TTP is reported to be extremely rare in allo-HSCT recipients. Therefore, we conducted this observational study to analyze the clinical manifestations, laboratory profiles, and prognosis of posttransplant TTP and further compared TTP with high-risk TA-TMA to provide more clinical information for TTP and the differential diagnosis of TMA after transplantation. Methods This retrospective cohort study used a nested case‒control approach. TTP after allo-HSCT was diagnosed on the basis of clinical presentation (the presence of both thrombocytopenia and microangiopathic hemolytic anemia with schistocytes seen on blood smears) and severe ADAMTS13 deficiency (< 10%), and cases were matched to three high-risk TA-TMA controls according to the year of allo-HSCT (± 1 year). High-risk TA-TMAs were diagnosed according to the 2023 harmonizing definitions for the diagnostic criteria of TA-TMA. Results A total of 26 patients with TTP were identified, including 15 (57.7%) males and 11 (42.3%) females, and the median age at allo-HSCT was 32 years (interquartile range [IQR]: 23‒54 years). The most common primary disease was acute myeloid leukemia (38.5%), followed by myelodysplastic syndrome (30.8%) and acute lymphoblastic leukemia (19.2%). The median time of TTP onset was 66.0 days (IQR: 41.8–306.8 days) after allo-HSCT. Compared with the 78 high-risk TA-TMA controls, the TTP patients had significantly lower ADAMTS13 activity levels (4.0% vs. 55.5%, p < 0.0001), and the proportion of patients with ADAMTS13 antibodies was greater (53.8%vs. 0, p < 0.0001). Among TTP patients, the most common types of end-organ damage occurred in the kidneys (69.2%), gastrointestinal tract (65.4%), central nervous system (CNS) (50.0%), serous cavity (26.9%), cardiovascular system (22.5%), and lungs (11.5%). The gastrointestinal tract appeared to be the earliest involved organ (median [IQR]: 0.0 [-5.0‒6.0] days after TTP diagnosis), followed by the kidneys (3.5 [-4.3‒13.8] days), cardiovascular system (7.5 [-7.0‒23.3] days), CNS (8.0 [4.0‒22.0] days), serous cavity (9.0 [-5.0‒14.0] days) and lungs (23.0 days). Compared with high-risk TA-TMA patients, TTP patients had greater proportions of CNS (50.0% vs. 19.2%, p = 0.002) and gastrointestinal dysfunction (65.4% vs. 32.1%, p = 0.003), and CNS dysfunction manifested later (8.0 days [IQR: 4.0‒22.0 days] vs. -1.0 days [IQR: -3.0‒4.0 days] since the diagnosis of TMA, p = 0.008). After the last follow-up, TTP patients had a significantly lower OS rate than high-risk TA-TMA patients did (26.9% vs. 48.7%, log rank p = 0.026). Most deaths (78.9%) among TTP patients occurred within 2 months after the onset of TTP; on this basis, the TTP patients could be divided into a high-risk group (aged > 40 years at the time of TTP diagnosis) and a low-risk group (aged < 40 years), with 2-month OS rates of 0% and 78.6%, respectively (log rank p < 0.0001). Additionally, patients with and without cardiovascular and pulmonary manifestations had 2-month OS rates of 0% and 57.9% (log rank p = 0.0098), respectively. Notably, different OS rate between the two risk groups could be partially explained by the higher incidence of cardiovascular and pulmonary manifestations in the high-risk group compared with the low-risk group (50.0% vs. 7.1%, p = 0.0026). Conclusions This is the first report focusing on TTP after allo-HSCT. Compared with high-risk TA-TMA patients, TTP patients had greater proportions of CNS and gastrointestinal dysfunction. Moreover, TTP patients had a significantly lower OS rate than high-risk TA-TMA patients did. Age > 40 years at the time of TTP diagnosis was considered to indicate high-risk TTP after allo-HSCT and was significantly associated with a poor prognosis. The results of this study indicate that mechanism-based TMA classification has practical clinical significance.