Late mortality, secondary malignancy and hospitalisation in teenage and young adult survivors of Hodgkin lymphoma: report of the Childhood/Adolescent/Young Adult Cancer Survivors Research Program and the BC Cancer Agency Centre for Lymphoid Cancer

Abstract

Late complications affecting Hodgkin lymphoma (HL) survivors are well described in paediatric and adult-based publications. This study determined the late morbidity and mortality risk for 442 teenage and young adult (TYAs) 5-year HL survivors, diagnosed at 15-24 years of age between 1970 and 1999, identified from the British Columbia Cancer Registry. Treatment details were abstracted from charts. Survivors and a matched comparison cohort were linked to provincial administrative health datasets until December 2006 and regression analysis was performed, providing risk ratios regarding mortality, secondary malignancy and morbidity causing hospitalisation. Sixty (13·6%) survivors experienced late mortality with excess deaths from secondary cancer [standardised mortality ratio (SMR) 18·6; 95% confidence interval (CI) 11-29·4] and non-malignant disease (SMR 3·6; 95% CI 2·2-5·5). Excess secondary cancers (standardised incidence ratio 7·8; 95% CI 5·6-10·5) were associated with radiotherapy [Hazard ratio (HR) 2·7; 95% CI 1-7·7] and female gender (HR 1·8; 95% CI 1-3·4). Of 281 survivors treated between 1981 and 1999, 143 (51%) had morbidity resulting in hospitalisation (relative risk 1·45; 95% CI 1·22-1·73). Hospitalisation significantly increased with combined modality therapy, chemotherapy alone and recent treatment era. TYA HL survivors have excess risk of mortality and secondary malignancy continuing 30 years from diagnosis. Radiotherapy is associated with secondary malignancy and current response-adapted protocols attempt to minimise exposure, but late morbidity causing hospitalisation remains significant.

Hodgkin lymphoma in children, adolescents and young adults – a comparative study of clinical presentation and treatment outcome

“…Since OS did not differ between the groups with the available follow-up time, this study calls for the need of investigating the occurrence of late effects, such as hospitalization [21], secondary AML [22], breast cancer and other secondary malignancies [23,24] heart and lung diseases [25], future fertility [26] and the risk of sick leave and disability pension [27] between children and adults receiving different treatment concepts.…”

Long-term hospitalisation rates among 5-year survivors of Hodgkin lymphoma in adolescence or young adulthood: A nationwide cohort study

“…One other study has done so18 but, as it was based on only 281 individuals, it was unable to provide risk estimates with any precision. Several studies of cause‐specific mortality in survivors of Hodgkin lymphoma diagnosed in childhood or early adult life have been carried out,19, 20, 21 and the risk of hospitalisation among survivors of all types of cancer diagnosed in adolescence and young adulthood has been studied in other populations 22, 23, 24, 25.…”

“…2 and 3). Several other studies have reported increases in incidence or mortality from infections either in survivors of Hodgkin lymphoma,9, 18 or in broader groups of cancers diagnosed in teenagers and young adults22, 24, 25 but none of these studies has revealed the extent of the disease burden from infections, as they have all considered only infections classified in Chapter II of the ICD, rather than bringing together all infections irrespective of where they appear in the ICD.…”

Multiple primary tumours: challenges and approaches, a review

“…9 Secondary malignancies are one of the most relevant causes for mortality in Hodgkin's lymphoma survivors. 27 Secondary leukaemia and myelodysplastic syndromes are associated with combination chemotherapy, especially etoposide in a dose-dependent manner. Etoposide-related leukaemia is distinguished from other forms of leukaemia that can be induced by alkylating agents by characteristics such as a shorter time from the end of treatment to development of leukaemia and evidence of translocation 11q23 or 21q22.…”