Predicting the prognosis of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) has been a moving target over the last several years. While earlier prognostic models relied mainly on such clinical variables as age, stage of disease, and performance status, it has become evident from gene-expression microarray studies that DLBCL is a heterogeneous disease in terms of molecular pathogenesis and cell of origin. Despite providing considerable insight into disease biology, these techniques are not widely available and are, at least at present, not applicable to routine clinical practice. Furthermore, older prognostic models need to be revalidated and modified as improved therapeutic options become available. In this review, we discuss pertinent studies on individual biomarkers and pattern-based biomarker models, with an emphasis on markers evaluated in patients treated with rituximab-containing chemotherapy. We also discuss recent and ongoing therapeutic trials using drugs that target molecular markers and pathways involved in the pathogenesis of DLBCL or those that adversely influence prognosis. The ultimate goal of these efforts is to refine prognostication of DLBCL using widely available, reproducible, and consistently predictive biomarker models applicable to currently used chemoimmunotherapy, and to create a pathophysiologically based framework for the rational design of individually tailored therapy.

The frequency and clinical significance of secondary thrombocytopenia following initial engraftment in autologous hematopoietic progenitor cell transplantation (HPCT) is unknown. An institutional review board approved retrospective study of thrombopoiesis was performed in 359 patients transplanted with autologous blood (97%) or marrow (3%) who achieved platelet engraftment to >50,000/microL. Idiopathic secondary posttransplant thrombocytopenia (ISPT) was defined as >50% decline in blood platelets to <100,000/microL in the absence of relapse or sepsis. ISPT occurred at a median of day +35 posttransplant in 17% of patients. Patients with ISPT had similar initial platelet engraftment (median 17 days) versus non-ISPT patients (18 days; P=NS) and recovered platelet counts (median 123,00 K/microL) by day 110 posttransplant. Four factors were independently associated with post-transplant death in a multivariate model: disease status at transplant; the number of prior chemotherapy regimens, failure to achieve a platelet count of >150,000/microL posttransplant, and the occurrence of ISPT. A prognostic score was developed based upon the occurrence of ISPT and posttransplant platelet counts of <150,000/microL. Survival of patients with both factors (n=25) was poor (15% alive at 5 years); patients with 1 factor (n=145) had 49% 5-year survival; patients with 0 factors (n=189) had 72% 5-year survival. Patients who failed to achieve a platelet count of >150,000/microL received significantly fewer CD34+ cells/kg (P<.001), whereas patients with ISPT received fewer CD34+CD38- cells/kg (P=.0006). The kinetics of posttransplant thrombopoiesis is an independent prognostic factor for long-term survival following autologous HPC. ISPT and lower initial posttransplant platelet counts reflect poor engraftment with long-term and short-term repopulating CD34+ hematopoietic stem cells, respectively, and are associated with an increased risk of death from disease relapse.

No abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal condition characterized by excessive immune activation. HLH can occur as a familial or sporadic acquired disorder. Acquired HLH is more frequently found in adults and is commonly secondary to infections, malignancies, or autoimmune diseases. Diagnosing HLH is challenging because of the rare occurrence, variable presentation, and nonspecific findings of this disorder. Diagnosis of HLH can be based on the diagnostic criteria which were used in the HLH-2004 trial. Given the rarity of this disease, protocols for its treatment have developed slowly, and obtaining adequate short-term and long-term control of the disease continues to be a challenge. Conventional induction therapy for HLH is dexamethasone and etoposide (VP-16), followed by or with cyclosporine. Intrathecal methotrexate ± hydrocortisone is given to those with central nervous system disease. We are reporting a patient who was diagnosed with Epstein-Barr virus (EBV) related HLH. He achieved complete remission with rituximab alone. To our knowledge, this is the first case of an adult patient with EBV related HLH who went into remission with rituximab therapy alone, without using the conventional chemotherapy.