Thrombotic thrombocytopenic purpura (TTP) may rarely complicate Allo-SCT.1, 2 First-line therapy of TTP is plasma exchange.3 However, other therapeutic approaches, such as steroids, i.v. high-dose Ig and vincristine, are still used. Despite anecdotally, recently, the anti-CD20 monoclonal antibody rituximab has been reported to successfully cure SCT-associated thrombotic microangiopathy.4, 5, 6, 7
Here, we report our experience on the use of rituximab in two patients with TTP developed after Allo-SCT. Two female patients were scheduled to receive Allo-SCT for their acute leukemia (Table 1). At days +74 and +26 after stem cell infusion, respectively, blood chemistry exams revealed hemolysis: anemia, high-unconjugated bilirubin and lactate dehydrogenase (LDH), low haptoglobin level and reticulocytosis with morphological evidence of schistocytes on peripheral blood films. Clotting parameters were normal and both direct and indirect antiglobulin tests were found negative. ADAMTS13 levels were found low in both patients. All these features were retained consistent with the diagnosis of TTP. CsA was discontinued and patients were treated with methyl-prednisolone, plasmapheresis with plasma exchange, defibrotide, and high-dose Ig without any benefit. Rituximab was then given at 375 mg/m2 weekly for three and two doses, respectively. We observed a slow but constant increase of plt count with amelioration of hemolytic laboratory parameters. As shown in Figure 1, in the case A complete blood cell count returned rapidly to normal values after the third dose. Rituximab was given monthly at the same dosage as maintenance therapy for four consecutive times. The patient died of bronchopneumonia 10 months later. In contrast, despite plt count and Hb level increased along with LDH level reduction, patient B died because of hepatic and renal failure due to acute GVHD at +51 days after Allo-SCT.
SCT-associated TTP is probably due to endothelial injury and is defined as a condition in which are seen the simultaneous occurrence of laboratory findings of hemolysis with schistocytes on the blood film, need for packed red cell transfusions, de novo or prolonged thrombocytopenia caused by consumption in absence of positive laboratory tests of disseminated intravascular coagulation.1, 2 The consensus on specific and standardized therapies for SCT-associated TTP is far from uniform. Results of plasma exchange are poor compared with those obtained in the novo TTP and mortality rate of patients treated with this modality still remains high (>80%).8
There is increasing evidence that the use of the chimeric monoclonal antibody against CD20 antigen rituximab has a role in the treatment of thrombotic microangiopathy complicating Allo-SCT such as TTP. In fact, very recently, anecdotal cases have been published on the use of rituximab in these cases. Only seven patients with thrombotic microangiopathy complicating Allo-SCT treated with rituximab have been reported to date. The present report, along with previously published experiences, suggests a role of B lymphocytes in the pathogenesis of Allo-SCT-associated TTP and supports further the use of rituximab in the management of this often life-threatening and severe complication. However, because of the limited number of cases treated, further studies need to be performed before drawing any definite conclusions.
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Carella, A., D'Arena, G., Greco, M. et al. Rituximab for allo-SCT-associated thrombotic thrombocytopenic purpura. Bone Marrow Transplant 41, 1063–1065 (2008). https://doi.org/10.1038/bmt.2008.25
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