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Second malignancy after childhood NHL
A
B
Figure 3. Estimated cumula- tive incidence of second malig- nant neoplasms (SML) 20 years after non-Hodgkin lym- phoma (NHL)-diagnosis in 3,590 NHL-patients <15 years of age, treated in one of the consecutive NHL-BFM studies NHL-BFM-81, through EURO- LB-02/B-NHL-04 according to
(A) Cumulative incidence of all SMN. (B) Cumulative incidence without basal-cell carcinoma (BCC). AML/MDS: acute myeloid leukemia/myelodys- plastic syndrome; SE: standard error, SLM: second lymphoid
the type of SMN.
malignancy.
risk factors for the development of AML/MDS, a diagno- sis of LBL (HR 12.0, 95%CI: 3.8-37.0, P<0.001), CNS-involvement (HR 5.2, 95%CI: 1.5-18.5, P=0.01) and a known CPC (HR 8.8, 95%CI: 1.2-67.3, P=0.04) showed a significant association.
Outcome after SMN
Survival at 10 years after diagnosis of the SMN was 47%, SE=6.4. The worst prognosis carrying AML/MDS with a 10-year survival of 26.5%, SE=11.6 was followed by CNS-malignancy with a 10-year survival of 43.6%, SE=15.5. Patients with solid secondary tumors outside the CNS had a 10-year survival of 50.8%, SE=13.0 and patients with second lymphoid malignancy 57.8%, SE=13.3, respectively. Patients with known CPC had a survival of only 11.1%, SE=10.5. Nine patients (six with known CPC) with SMN developed a third malignant neo- plasm (Tables 3 and 4).
Discussion
We presented the incidence and types of SMN as well as risk factors for the development of SMN in the to date largest cohort of patients who were treated for NHL as
children according to subtype-specific BFM-type therapy regimens with stable cumulative drug doses over the analysis period. The estimated 20-year cumulative inci- dence of SMN of 5.3±0.7% (4.8±0.7% without basal-cell carcinomas), among 3,590 patients is comparable to the one reported by Leung et al.10 in a cohort of 497 children with NHL (4.8±1.3% at 20 years). An analysis of 456 French and British 3-year survivors of pediatric NHL showed 25-year cumulative incidence of solid SMN of 10%, and a relative risk of 12%.1 The CCSS group report- ed a 20-year cumulative incidence of SMN of 3% (SIR of 3.9) in 1,082 5-year survivors of pediatric NHL.9 Since this study focused on solid-tumor SMN most of the AML/MDS that occured within 5 years of first NHL-diag- nosis and all secondary lymphomas were not included which explains the somewhat lower cumulative inci- dence compared to our study. In an updated CCSS-report from 2010, a 30-year cumulative incidence of 5.8% and SIR of 4.1% was reported for the same cohort of patients.8 The observation of an increasing cumulative incidence with longer observation time is reflected in our study by the missing plateau for secondary carcinomas after NHL-therapy.
Analyses in the US Surveillance, Epidemiology, and End Results (SEER) program showed a 5.3-fold elevated risk
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