Javier El-Bietar

T-cell therapies for Epstein-Barr virus-associated lymphomas.

Epstein-Barr virus (EBV)-associated lymphomas represent a broad spectrum of diseases and can be characterized by their pattern of viral latency. These pathologies display the importance of healthy T cell–mediated control of the EBV-infected B cells. Burkitts lymphoma is the least immunogenic and has a type I latency pattern. Hodgkins and a variety of non-Hodgkins lymphomas exhibit antigens of type II latency. Posttransplant lymphoproliferative disease in the solid organ and hematopoietic stem cell transplant setting as well as lymphomas arising in primary immunodeficiency patients are tumors with type III latency. This last group expresses all 9 latent proteins and is the most immunogenic. T-cell approaches including donor lymphocyte infusions and the adoptive transfer of EBV-specific cytotoxic T lymphocytes can be used to treat these diseases. The authors describe the biology of these EBV-associated lymphomas and review the methodology and outcomes of existing T cell–based therapies as well as strategies to improve their efficacy.

Complications of Transplant for Nonmalignant Disorders: Autoimmune Cytopenias, Opportunistic Infections, and PTLD

Advances in supportive care have led to significant improvements in hematopoietic cell transplant (HCT) outcomes over the last decade. Although children with acute leukemia previously had rates of 1-year transplant-related mortality (TRM) following unrelated donor HCT approaching 40%, in a more recent era, these rates have fallen bymore than half to approximately 15% [1]. This has led to significantly more alternative donor HCTs being performed for a wide variety of nonmalignant diseases, including primary immunodeficiencies (of T cells and/or phagocytes), hemoglobinopathies, bone marrow failure syndromes, and metabolic syndromes. Unlike a typical patient with leukemia, who enters HCT having received months of immunosuppressive chemotherapy, many patients with a nonmalignant disorder will begin the conditioning regimen with a fully intact immune system. This places those patients at very high risk for graft rejection, which forces transplant physicians to employ preparative regimens that are highly immunoablative. Even patients who enter HCT with defective immune systems, such as those with severe aplastic anemia or hemophagocytic lymphohistiocytosis, tend to require significant immunoablation because of an underlying disposition toward attacking bone marrow elements such as transplanted hematopoietic stem cells. This increased pre-HCT immunoablation often leads to delays in post-HCT immune reconstitution, which in turn is associated with significant complica-

Restrictive Palivizumab Use Does Not Lead to Increased Morbidity and Mortality in Pediatric Hematopoietic Stem Cell Transplantation Patients

Respiratory syncytial virus (RSV) is a common cause of infection in immunocompromised patients and can lead to significant morbidity and mortality in pediatric hematopoietic stem cell transplantation (HSCT) patients and patients with a primary immune deficiency (PID). Palivizumab is a humanized monoclonal antibody that targets the F glycoprotein on the surface of the RSV virus, preventing RSV replication. Palivizumab was initially licensed for the prevention of RSV infections in children at high risk of severe disease. Since licensure, the American Academy of Pediatrics (AAP) has issued guidelines to help ensure appropriate use of palivizumab in pediatric patients. In the 2014 edition of the guidelines, the AAP recognizes that severe and fatal disease secondary to RSV can be seen in patients receiving chemotherapy or patients who are immunocompromised because of other conditions. However, they recognize that no large clinical trials exist to support the use of palivizumab, and efficacy and safety data in this population are limited. Despite this, the AAP recommends considering prophylaxis for children younger than 24 months who are profoundly immunocompromised during the RSV season. Because of the high cost of palivizumab, the uncertainty of its efficacy as prophylaxis in hospitalized pediatric HSCT and PID patients, and secondary to recent data from our center that suggested immunocompromised patients diagnosed with RSV did not have worse outcomes, we implemented very restrictive criteria for the use of palivizumab in the 2015 to 2016 RSV season in our pediatric HSCT population. Despite these strict criteria, there was no change in the number of patients developing RSV during this season compared with previous seasons, and there was no change in RSV course in those patients developing RSV compared with previous seasons. Restricted use also resulted in a significant dose and cost savings. Based on our experience, we recommend only administering prophylaxis palivizumab to the youngest and most high-risk HSCT patients during the RSV season.