Key Points A subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

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Hepatitis is a rare complication of herpes simplex virus (HSV), often leading to acute liver failure (ALF), liver transplantation (LT), and/or death. Our aim was to identify variables associated with either survival or progression (death/LT), based on an analysis of cases in the literature and our institution. A total of 137 cases (132 literature, 5 institutional) of HSV hepatitis were identified. The main features at clinical presentation were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients. Most cases (58%) were first diagnosed at autopsy and the diagnosis was suspected clinically prior to tissue confirmation in only 23%. Overall, 74% of cases progressed to death or LT, with 51% in acyclovirtreated patients as compared to 88% in the untreated subjects (P ϭ 0.03). Variables on presentation associated with death or need for LT compared to spontaneous survival: male gender, age Ͼ40 yr, immunocompromised state, ALT Ͼ5,000 U/L, platelet count Ͻ75 ϫ 10 3 /L, coagulopathy, encephalopathy, and absence of antiviral therapy. In conclusion, HSV hepatitis has a high mortality and is often clinically unsuspected. Patients who are male, older, immunocompromised, and/or presenting with significant liver dysfunction are more likely to progress to death and should thus be evaluated for LT early. Based on the frequent delay in HSV diagnosis, low risk-benefit ratio, and significantly improved outcomes, empiric acyclovir therapy for patients presenting with ALF of unknown etiology is recommended until HSV hepatitis is excluded.

A B S T R A C T PurposeAdult post-transplantation lymphoproliferative disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. MethodsWe examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). ResultsEighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P Ͻ .0001) and 33% (P ϭ .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P ϭ .01; OS, 3.61; P ϭ .04), bone marrow involvement (PFS, 2.95; P ϭ .03; OS, 3.14; P ϭ .03), and hypoalbuminemia (PFS, 2.96; P ϭ .05; OS, 3.64; P ϭ .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, Ն 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P Ͻ .0001). ConclusionThis large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.