Foiling IL-6 to treat B-lymphoproliferative disorder

Approximately 21 000 solid organ transplantations are performed annually in the United States. These transplantations offer hope to those about to die of a failing heart, a hepatitis C–ravaged liver, or severe chronic obstructive pulmonary disease, or they improve the quality of life for those on chronic dialysis. But the dark side of solid organ transplantation is the need for long-term immunosuppression to prevent organ rejection. This results in a substantial risk of Epstein-Barr virus–driven B-lymphoproliferative disorder (BLPD), ranging from approximately 1% in kidney-transplant recipients to 5% in heart-transplant recipients, and possibly higher in lung-transplant recipients. Treatment of BLPD has been challenging. Unlike patients with other types of aggressive non-Hodgkin lymphoma, patients with BLPD can be cured by resection of localized disease (often pulmonary nodules). Interferon alpha, multiagent systemic chemotherapy, or rituximab can also be curative. Haddad and colleagues (page 1590) used the observation that IL-6 is a growth factor for EBV-infected B lymphocytes to design a novel treatment approach for these patients. They treated 12 solid organ–transplant recipients who developed BLPD, with an anti–IL-6 monoclonal antibody. After daily injections of the anti–IL-6 monoclonal antibody for 15 days, 5 patients achieved a complete response and 3 patients achieved a partial response. No major toxicity was observed, and the remissions were durable in most patients. How will anti–IL-6 therapy fit into the panoply of treatments for B-lymphoproliferative disorder? This will require further study and larger numbers of patients.