FP799EFFICIENCY OF RITUXIMAB THERAPY IN CHILDREN WITH RENAL THROMBOTIC MICROANGIOPATHY ASSOCIATED WITH HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract

Introduction and Aims: Hematopoietic stem cell transplantation (HSCT) related thrombotic microangiopathy (TMA) occurs in 10-20% of transplant recipients. It is a challenging post-transplant complication associated with long term morbidity. Since the underling mechanisms for HSCT-TMA is complex and not well understood, the current treatment strategy is suboptimal. Method(s): Wepresent the successful treatment of HSCT-TMA with Rituximab. Result(s): Five-year old boy with aplastic anemia presented with blood hypertension, progressed Coombs negative anemia (reduction of hemoglobin from 103 to 85 g/l) and renal dysfunction (proteinuria 0,3 g/day, decease of eGRR from 104 to 74 ml/min/1,73m2)on 4mo after allogenic ABO-compatibility HSCT (TCR ab/CD19 depletion). Conditioning regimen included Fludarabine, Cyclophosphamide, Thymoglobuline; the boy consistently received graft-versus-host disease (GVHD) prophylaxis with Cyclosporine (2 mg/kg/d from-7day; acute nephrotoxicity on day +30), Methotrexate (7,5 mg/m2/week from +31day; leucopeniaon day +77), Mycophenolate mofetil (750 mg/m2/d; from +78 day to +136 day; anemia), the standard infection prophylaxis; considering low serum IgG level (2,5-4,6 g/l) he received IVIG (0,5 g/kg/2 week). There were no obvious signs of acute and chronic GVHD in the patient. Laboratory investigation revealed: red cell fragmentation (6-8%, N<2%), decreased haptoglobin (0,2 mg/l, N=0,3-2 mg/l) and vitamin B12 level (107 ng/l, N=150-400), normal levels of blood platelet, homocysteine and folate, normal blood lactate dehydrogenase (233-322 U/l) and C3, C4 activity; blood tests for Aspergillus, Cytomegalovirus (CMV), BK-virus and bone marrow test for Parvo-19, CMV were negative. The patient had severe proteinuria (4,4g/m2/day), normal urine sediment and kidney US. A renal biopsy showed mesan-gial proliferation, diffuse enlargement of subendothelial space with fibrin deposition, capillary lumen narrowing typical for TMA. Treatment with Prednisone (1mg/kg/day) during 4week was ineffective.Treatment with Rituximab 375 mg/m2/week @4led to the normalization of blood pressure, hemoglobin's level, complete disappearance of proteinuria (at 3 months from therapy) and partial recovery of renal function (eGFR 87 ml/min). Conclusion(s): Our clinicalcase demonstrates that HSCT-TMA primarily limited to the renal microvasculature and manifested by blood hypertension and renal dysfunction. The development of disease in the absence of main risk factors for HSCT-TMA such as donor/recipient ABO-incompatibility, high-intensity myeloablative conditioning regimen, GVHD, current therapy with calcineurin inhibitor, and the absence of thrombocytopenia and increased blood LDH activity throughout the period of patient's observation were the peculiarities of the case. We suppose that laboratory screening for HSCT-TMA would beperformedinall HSCT-patients, kidneybiopsy should be considered in uncertain cases in patient with unexplained renal dysfunction. We assume that the efficiency of Rituximab therapy can prove the immune mechanism (subacute renal GVHD?) of HSCT-TMA in our case.* We are grateful to E.Stolyarevich and P. Povilaitite for their assistance with the histology.