Immunoadsorption and autologous transplantation for life-threatening primary antiphospholipid syndrome

Anne Angelillo-Scherrer, Behrouz Mansouri Taleghani, Frauke Förger, Gabriela M. Baerlocher, Thomas Pabst, Alexander Pöllinger, Yara Banz, Thomas Geiser, Johanna A. Kremer Hovinga and Alicia Rovó

Article Figures & Data


  • Figure 1.

    Diffuse alveolar hemorrhage. (A) The contrast-enhanced thoracic-computer tomography shows widespread patchy ground glass opacification and, in part, a faint “crazy paving” pattern. The contrast between the ground glass areas caused by diffuse alveolar hemorrhage and the air containing bronchi render the bronchi more prominent (dark bronchus sign). There were no signs of pulmonary embolism nor signs of active bronchial artery bleeding. (B) Images of cytological bronchoalveolar lavage specimens. (Upper) Routine Papanicolaou staining shows macrophages (50%-60%) and a significant number of neutrophils, as well as lymphocytes. Almost all macrophages contain a brown-yellow pigment in the cytoplasm. (Lower) Prussian blue staining shows an area with more prominent macrophages, of which most stain intensely blue, denoting iron, reflecting severe intra-alveolar hemorrhage (∼95% of the total macrophage population were hemosiderin-laden macrophages, Golde score 250). Magnification, 40×.

  • Figure 2.

    Major events in the clinical course and laboratory results. Shown are the antiphospholipid immunoglobulin G antibody titers (blue line: anticardiolipin; red line: anti-β2-glycoprotein 1) and apheresis cycles. The arrows indicate events and points of intervention. The variation in the anticardiolipin and anti-β2-glycoprotein 1 immunoglobulin G antibody titers until day 315 reflects management with immunoadsorption. Dosages of administered therapy are as follow. Corticosteroids: day 0 to day 79: methylprednisolone boluses (500 mg daily IV) for 3 days followed by prednisone 1 mg/kg daily; day 101 to day 444: methylprednisolone boluses (1000 mg daily IV) for 3 days, followed by prednisone 1 mg/kg per day tapering and withdraw. Rituximab: 375 mg/m2 weekly for 4 weeks. Cyclophosphamide: pulses 750 mg/m2 every 3 weeks. Mycophenolate mofetil: 1 g daily for 1 week, followed by 1 g twice daily. Pravastatin: 40 mg daily. Bortezomib: 1.3 mg/m2 every 72 hours × 5 doses. Peripheral blood stem cell mobilization: cyclophosphamide: 2 g/m2 given IV and granulocyte colony-stimulating factor (filgrastim) at 10 µg per kilogram of body weight administered subcutaneously daily beginning 3 days later. Peripheral blood stem cell collection was performed 10 days after the initiation of the mobilization. The time interval between the apheresis collection of peripheral blood stem cells and the start of the conditioning regimen was 3 days. Conditioning regimen: From day −5 to day −2 (ie, from 5 days to 2 days before transplantation), the patient received a conditioning regimen consisting of cyclophosphamide 50 mg per kilogram of body weight per day given IV on days −5, −4, −3, and −2 (total dose, 200 mg/kg) and equine anti-thymocyte globulin (ATGAM Pfizer) 30 mg per kilogram of body weight given IV on days −4, −3, and −2 (total dose, 90 mg/kg body weight). Immunoadsorption: a total of 12 treatment cycles (4-9 treatments/cycle) were performed. The duration of each treatment was 225-300 minutes. CU, chemiluminescent units; MMF, mycophenolate mofetil; Ritux, rituximab.