Autoimmune cytopenias complicating hematopoietic cell transplantation

Abstract

Immune cytopenias after allogeneic hematopoietic cell transplantation are rare, albeit increasingly recognized, complications. Autoimmune diseases are serious complications of HCT and include immune-mediated cytopenias i.e. autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia. Severe cytopenia is usually defined by decreases of hemoglobin concentration below 7 g/dL, of platelet count below 20 G/L, or of absolute granulocyte count below 0.5 G/L, and it is mediated by the presence of auto-antibodies. ITP occurring in combination with AIHA is known as Evans syndrome. Immune dysregulation is caused by impaired immune reconstitution and/or loss of self-tolerance. Primary risk factors of autoimmune cytopenias include: peripheral blood or cord blood as a stem cell source, unrelated HCT, non-malignant disease, use of alemtuzumab, acute/chronic graft-versus-host disease (GvHD), cytomegalovirus reactivation, infections, and, in pediatric settings, conditioning omitting total body irradiation. Diagnosis of autoimmune cytopenia is challenging due to a broad differential diagnosis: primary or secondary graft failure, infections, GvHD, disease relapse, drug-induced side effects, transplant-associated thrombotic microangiopathy, ABO-incompatibility, or disseminated intravascular coagulation. Treatment should be tailored to the individual patient, and ranges from watchful waiting to aggressive management in life-threatening situations. Apart from specific treatment adjusted for specific cytopenia, supportive care should include transfusions of leukocyte-reduced and irradiated red blood cell concentrates or pathogen-reduced platelet concentrates; treatment of infections and GvHD; modification of immunosuppression; and supplementation with microelements. Autoimmune cytopenias are usually highly resistant to standard therapy and are associated with increased risks of high morbidity and mortality, particularly when coexisting with other post-transplant complications.