Risk of Subsequent Malignant Neoplasms Is Low in Children With Hodgkin Lymphoma

A study published in Blood suggests that children and adolescents with intermediate-risk Hodgkin lymphoma have a relatively low cumulative risk of developing subsequent malignant neoplasms (SMNs), but radiation therapy appears to increase the risk of SMNs in these patients. The findings were published by Lisa Giulino-Roth, MD, of the Weill Cornell Medical College in New York, and colleagues from the Children’s Oncology Group.

In this analysis, researchers studied a group of 1,734 children, adolescents, and young adults who received a new diagnosis of intermediate-risk Hodgkin lymphoma between 2002 and 2009 who participated in the Children’s Oncology Group phase III study AHOD0031.

This trial evaluated a response-adapted therapeutic approach designed to mitigate long-term toxicities in Hodgkin lymphoma, while ensuring the maintenance of high cure rates. All eligible participants were treated with response-based therapy consisting of four cycles of a chemotherapy backbone comprising doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Treatment was administered with or without field radiation therapy.

Patients who were determined to have a rapid early response after two cycles of ABVE-PC and a complete response following four cycles were randomized to receive 21 Gy involved field radiation therapy (IFRT) or no further therapy. In contrast, patients with a slow early response to two cycles of ABVE-PC received a total of four cycles of ABVE-PC, with or without an additional two cycles of dexamethasone, etoposide, cisplatin, cytarabine (DECA). All patients with a slow early response received IFRT.

There were no differences in baseline clinical or demographic characteristics between patients with or without subsequent malignant neoplasms (SMN), but radiation therapy, non-white race, and B symptoms were associated with a higher SMN risk.

The researchers performed an assessment of SMNs at a median follow up of 7.3 years, as well as event-free survival (EFS) and overall survival (OS).

At time of diagnosis, the mean age of the overall cohort was 14.5±3.4 years. The estimated 10-year EFS was 81.5% and the 10-year OS was 96.1%.

A total of 17 patients developed an SMN during follow-up (1%), while the remaining 1,694 patients had no SMN. Across the entire cohort, the 10-year cumulative incidence of SMN was 1.3%. SMNs included:

  • acute myeloid leukemia (AML; n=3)
  • solid tumors (n=11)
  • non-Hodgkin lymphoma (n=3)

There were no differences between patients with versus without SMN at baseline in terms of clinical or demographic characteristics, the authors noted. “Of note, none of the patients with therapy-related AML in our cohort received DECA, which is relevant as excess risk for leukemia has been reported following treatment with etoposide and cisplatin,” they added.

As seen in the TABLE, the standardized incidence ratio for any SMN was 9.5, with a corresponding absolute excess risk of 1.2 per 1,000 person-years.

Researchers reported that the cumulative incidence of SMNs was significantly higher in patients who were treated with radiation therapy (p=0.037).

Other factors associated with SMN risk in a multivariate analysis included:

  • race (Asian vs. white: hazard ratio [HR] = 7.8; Black vs. white: HR=0.8; p=0.028)
  • B symptoms (HR=3.1; p=0.027)
  • receipt of radiation therapy (HR=8.6; p=0.040)

“The reasons for these associations, other than treatment with radiation therapy, remain unclear and these associations have not previously been noted,” the authors concluded, adding that the relatively short follow-up period was a limitation of this study. “Further follow-up with this cohort and in other cohorts is required to further evaluate these associations.”

Study authors report no relevant conflicts of interest.


Giulino-Roth L, Pei Q, Buxton A, et al. Subsequent malignant neoplasms among children with Hodgkin lymphoma: A report from the Children’s Oncology Group. Blood. 2020 December 11. [Epub ahead of print]