Lymphoblastic lymphoma (LBL) is a rare disease, comprising about 2% of all non-Hodgkin lymphomas (NHLs) in adults.[1] It is a highly aggressive subtype of lymphoma, most commonly of precursor T-cell origin, occurring most frequently in adolescents and young adults, with male predominance and frequent mediastinal, bone marrow, and central nervous system (CNS) involvement. The pathologic characteristics of LBL at the morphologic, phenotypic, and genetic levels are identical to acute lymphoblastic leukemia (ALL), and the World Health Organization Classification of Lymphoid Neoplasms has unified these entities as precursor T-cell or B-cell lymphoblastic leukemia/lymphoma.[2]
Treatment approaches to LBL in adults have developed separately from those for adult ALL. Patients with predominantly nodal disease at presentation have been designated as having LBL, whereas those with disease primarily in the marrow or peripheral blood have been classified as having ALL. This distinction has varied in the published literature and, coupled with the rarity of LBL, this has meant that optimal treatment approaches for adults with LBL have been difficult to determine. There has been a recent trend toward including patients with LBL on protocols designed for ALL, but emerging data from gene-expression profiling studies point to differences between precursor T-cell and B-cell disease with predominant nodal vs predominant marrow involvement, particularly for genes involved in interactions between malignant cells and the microenvironment.[3] Differences in T-cell receptor genotypes have also been reported between cases designated as LBL vs ALL.[4] As a result, the clinical distinction between these two entities still has relevance, and treatment approaches specific to LBL continue to be investigated.
Treatment
Lymphoblastic lymphoma is a clinically aggressive disease. It typically presents as widely disseminated disease, with frequent bone marrow involvement, bulky mediastinal disease, and a 5% to 10% incidence of CNS involvement at presentation, usually involving the leptomeninges. It is characterized by a high response rate to initial chemotherapy, but with a tendency toward early relapse with the CNS as a common relapse site. Currently used treatment regimens are therefore characterized by relatively intensive induction therapy, the prevention of CNS relapse, and the use of various types of postinduction therapy aimed at reducing the risk for subsequent relapse. Some regimens have included radiation therapy to the mediastinum for patients with high tumor burden at this site.
‘Standard Dose’ Chemotherapy and Chemoradiotherapy Regimens
Early chemotherapy trials adopted regimens designed for less aggressive subtypes of NHL, with poor results.[5‑9] For example, a study of 95 adult and pediatric patients treated with various NHL protocols without CNS treatment or prophylaxis reported a complete response rate of only 24%, with fewer than 10% of patients free of disease at 5 years.[5]
