Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. The majority of patients benefit from chemo-immunotherapy; however, 30 to 40% relapse after first-line treatment, and 10% are refractory to first-line treatment. This variability in outcome has led to the identification of prognostic factors to stratify patients based on their risk of relapse. The five-factor international prognostic index (IPI) was formulated for such risk stratification more than 20 years ago, based on clinical information obtained from patients with aggressive lymphomas treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like chemotherapy. The addition of rituximab to CHOP chemotherapy led to improved outcomes, diminishing the discriminatory capacity of IPI amongst risk groups. Efforts to enhance the prognostic model by adding or defining new factors have only led to minor improvements without the ability to identify patients at risk of an inferior outcome.

Intravascular B cell lymphoma (IVBCL) is notoriously difficult to diagnose as the clinical manifestations are protean, and the patterns seen with routine labs and imaging are non-specific. Furthermore, the disease follows an aggressive course and is often fatal within a matter of weeks to months from symptom onset, unless recognized and treated appropriately. This has historically meant that diagnosis was made at autopsy for many patients. Over the past few decades, however, scientific and clinical literature have slowly accumulated to better characterize and raise clinical awareness of this disease. In this paper, we will review the characteristics that make this diagnosis challenging, and then discuss new and emerging diagnostic avenues.

Flavopiridol (FVP; alvocidib), an FDA-approved orphan drug, has been studied in clinical trials under both single treatment and combination scenarios; several singleagent Phase I and Phase II clinical trials against leukemia, lymphomas, and solid tumors are active. To date, there have been more than 50 clinical trials involving FVP in the United States. Unfortunately, almost half of patients on FVP clinical trials showed serious adverse effects, implicating appropriate dosages need to be found and an alternative way to circumvent the toxicity of FVP with synergistic agents.

Approximately 20% of adult patients with Burkitt's lymphoma (BL) have relapsed/refractory disease, which is characterized by poor overall survival (OS) and virtually no therapeutic options after failure of two lines of chemotherapy, due in part to the peculiarities of tumor cell biology. Improved treatment strategies are an unmet need for these patients. There have been individual attempts to use chimeric antigen receptor (CAR)-T therapy in this patient population using anti-CD19, CD20, and CD22 cells.