Anaplastic Large Cell Lymphoma: Contemporary Concepts and Optimal Management

Anaplastic Large Cell Lymphomas (ALCL) are clinically aggressive and pathologically distinct lymphoid neoplasms that originate from a mature post-thymic T-cell. The contemporary World Health Organization (WHO) Classification of Haematologic Malignancies recognizes two distinct subtypes of systemic ALCL: Anaplastic Lymphoma Kinase (ALK)-negative, and ALK-positive. An additional unique subtype of ALCL is known to arise after prolonged exposure to breast implants, known as Breast Implant Associated ALCL (BIALCL). While histologic features of ALCL subtypes have significant overlap, genomic studies suggest the unique pathophysiology and molecular events of tumorigenesis. As a group, ALCLs are rare among non-Hodgkin lymphomas comprising 1–3% overall. There seems to be age and geographic predilection with ALK-positive ALCL affecting younger individuals and being diagnosed more frequently in North America than Europe. Both subtypes are quite uncommon in Hispanic and Asian populations. ALK-positive ALCL patients have a better overall prognosis than those with ALK-negative ALCL, and clinical features at presentation (i.e., International Prognostic Index, IPI) define the outcome in both subtypes. Molecular events affecting DUSP22 and TP63 have been reported to predict survival outcomes as well, with former being favorable, and the latter an unfavorable prognostic marker. Multiagent CHOP-like chemotherapy remains a standard of care for newly diagnosed ALCL patients treated with curative intent and provide a chance of cure for the majority of ALK-positive ALCL patients, and at least half of the ALK-negative ALCL patients. The role of consolidative high-dose therapy and autologous hematopoietic stem cell transplantation remains unclear. Novel targeted agents are actively being investigated for their role in initial therapy. New immunoconjugates, targeted kinase inhibitors, and transgenic autologous T-cells are being studied in patients with relapsed and refractory disease. This review will discuss contemporary concepts in pathogenesis and management of systemic ALCL. The biology and management of primary cutaneous ALCL will be discussed elsewhere.