GRAFT FAILURE AFTER DENGUE FEVER INFECCION AND PSEUDO-THROMBOTIC MICROANGIOPATHY DUE TO SEVERE VITAMIN B12 DEFICIENCY IN A HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE REPORT

Abstract

Introduction: Allogeneic hematopoietic stem cell transplantation is an effective treatment for malignant hematopoietic diseases and the only curative option for Myelofibrosis (MF). Although most patients achieve rapid and stable hematopoietic recovery after allo-HSCT, graft failure remains a life-threatening complication and etiology is complex and usually multifactorial. Graft failure, including graft rejection and poor graft function, is defined as the failure to surpass a threshold Absolute Neutrophil Count (ANC) of 0.5×109/L after allo-HSCT. Case report: We report a 69-year-old male recipient of HLA-matched female sibling donor HSCT due to a high-risk primary MF, with reduced-intensity conditioning and GVHD prophylaxis consisting of post-transplantation cyclophosphamide and cyclosporine. Engraftment occurred on D+17, full donor chimerism was achieved and immunosuppression was tapered and suspended on D+78. One week later, the patient presented at the emergency room with fever, retro-orbital and lower limb pain and was diagnosed with severe dengue fever and pancytopenia required blood transfusion and other supportive treatment such as epoetin alfa, granulocyte colony-stimulating factorand thrombopoietin receptor agonist, leading to full cytopenia recovery. At that time, chimerism analysis was 94% and bone marrow revaluation revealed a grade 2 fibrosis with multilineage dysplasia. On D+162, a sudden worsening of all hematological parameters, appearance of schistocytes in peripheral blood, increase in lactic dehydrogenase, reduction in haptoglobin and normal reticulocyte count, in the absence of infections and negative antiglobulin testing, raised the fear of thrombotic microangiopathy but low level of measured vitamin B12 level and partial improvement after supplementation raised the hypothesis of pseudomicroangiopathy. Unfortunately chimerism confirmed graft failure only showing host autologous hematopoiesis. Conclusion: Graft failure and poor graft function can result in significant morbidity and mortality after allo HSCT. These two entities are discriminated in terms of donor chimerism. Use of toxic drugs, presence of GVHD, vitamin deficiency and viral infections must be assessed before the diagnosis. Erythropoietin, growth factor support or thrombopoietin receptor agonists may be useful. Also CD34+ stem cell infusion without conditioning regimen may be useful for poor graft function and a second allogeneic stem cell transplantation may be feasible after GF in first allo HSCT.