Refractory secondary thrombotic microangiopathy in two systemic disorders with remission after autologous haematopoietic stem cell transplantation: a case series

Abstract Background Secondary thrombotic microangiopathy (TMA) may complicate catastrophic antiphospholipid syndrome (CAPS) and monoclonal gammopathy-associated disorders. In refractory disease, conventional haematological markers may not reflect ongoing organ injury, and evidence supporting autologous haematopoietic stem cell transplantation (AHSCT) is limited. Case presentation Patient A was a 15-year-old girl with systemic lupus erythematosus and antiphospholipid syndrome who subsequently developed CAPS with multiorgan involvement and dialysis-dependent kidney failure. Intensive immunosuppression, plasma exchange, anticoagulation, and complement inhibition achieved partial clinical and haematological control, but serious cardiac and cerebrovascular events occurred thereafter, accompanied only by transient changes in platelet count and lactate dehydrogenase. Following AHSCT in 2018, relevant autoantibodies became negative, and no clinical recurrence of systemic lupus erythematosus, antiphospholipid syndrome, or TMA occurred during more than 8 years of follow-up; she subsequently underwent successful kidney transplantation. Patient B was a 37-year-old man with an IgG-lambda monoclonal protein, plasmacytomas, features of Castleman disease, and a POEMS syndrome-like phenotype without polyneuropathy. Serial kidney biopsies demonstrated progressive kidney-limited TMA despite normal systemic haemolysis markers and treatment with ravulizumab and clone-directed therapy. Kidney, constitutional, ophthalmological, and cardiac manifestations progressed. Eight months after AHSCT in 2025, symptoms and inflammatory markers improved, estimated glomerular filtration rate increased from 35 to 70 mL/min/1.73 m², urinary protein-to-creatinine ratio decreased from 2.05 to 1.17 g/g, and the monoclonal protein decreased from 4.6 to 2.0 g/L. Conclusions These cases illustrate that organ injury in secondary TMA may progress despite partial systemic response and without persistent abnormalities in conventional haematological markers. Assessment should therefore integrate organ-specific trajectories with systemic disease activity, with targeted reassessment when clinical findings and laboratory markers are discordant. Clinical improvement followed AHSCT in both patients, including durable remission in Patient A. Together with previous reports, these observations support considering AHSCT as a therapeutic option in selected patients with severe secondary TMA associated with a potentially transplant-responsive autoimmune or clonal disorder. Although published experience has predominantly involved treatment-refractory disease, this does not establish that AHSCT should be confined to rescue therapy; its optimal timing remains unknown. These observations do not establish the magnitude of any treatment effect or a routine organ-surveillance protocol.