The majority of lymphomas that occur in children and adolescents are non-Hodgkin lymphomas and, among them, approximately 25% to 35% are lymphoblastic lymphomas (LBLs). T cell lymphoblastic lymphomas (T-LBLs) are the most predominant type and account for an estimated 80% of cases; precursor B cell lymphoblastic lymphomas (pB-LBLs) represent the remaining 20%.

Treatment outcomes for patients with LBL have improved over the years. Current event-free (EFS) and overall survival (OS) rates for children with LBL exceed 80%. However, treatment can result in significant morbidity and late effects, particularly in patients with T-LBL and large mediastinal tumors. In addition, prognosis remains poor for those with refractory or relapsed disease. A review article published in the British Journal of Haematology discussed recent advances and challenges in treating pediatric LBL, as well as ongoing and future efforts to optimize therapy and develop novel targeted treatment approaches.

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Current Limitations

One of the most pressing challenges for improving outcomes is the need for “clear prognostic factors so that we can better risk stratify patients,” coauthor Michelle Hermiston, MD, PhD, associate professor in the department of pediatrics at the University of California in San Francisco, told Hematology Advisor. “The outcomes for patients with relapsed or refractory disease are dismal, making this largely a disease of one chance.”

She pointed out that it would be helpful to identify children, adolescents, and young adults with high-risk disease at diagnosis so they could receive novel treatments to improve their outcomes. “Novel approaches to therapy are also desperately needed as we are likely at, or close to, the ceiling in terms of toxicity of standard chemotherapies,” Dr Hermiston explained.

She added, “Better prognostic factors for patients with favorable disease are also needed. With cure rates this high, we are likely overtreating a significant number of children who would be cured with less intensive therapy. Being able to identify these distinct populations is a gap in the field.”

The median age of diagnosis for T-LBL is approximately 9 years of age, and men are affected 2 to 5 times more frequently than women. Although T-LBL can arise in any lymph node of the body, the mediastinum and cervical nodes are involved in most patients; in adolescents and young adults, presentation with an anterior mediastinal mass arising from the thymus is common.

In contrast, most precursor B lineage malignancies present as B-lymphoblastic leukemia (B-ALL), and B-ALL/LBL primarily occurs in young children under the age 6 years. Similar to T-LBL, B-ALL/LBL is more likely to occur in males, but in contrast to T-LBL, where patients generally present with high-stage disease, most patients with pB-LBL present with lower-stage disease. The disease presents most commonly at osteolytic bone lesions and skin or subcutaneous lesions but can also present as mediastinal or pleura disease, isolated bone marrow disease, or visceral disease.

Treatment

ALL-type treatment regimens are usually the front-line treatment and have achieved EFS rates of 75% to 90%. These regimens trace back to either the LSA2L2 protocol established at the Memorial Sloan Kettering Cancer Center in New York, New York, or the NHL-Berlin-Franklin-Munster (BFM) protocol that demonstrated the first durable cure rates in children with LBL. Nearly all treatment regimens for LBL in the United States and in western Europe use one of these early protocols as a “backbone.” Data on pediatric LBL in Asian studies are limited.