Risk of second primary cancer after Hodgkin's disease in patients in the British National Lymphoma Investigation: relationships to host factors, histology and stage of Hodgkin's disease, and splenectomy

Abstract

Summary The risks of second primary cancer were analysed in 2846 patients with Hodgkin's disease treated within the British National Lymphoma Investigation during 1970-87. The relative risk (RR) of leukaemia was significantly greater in women (RR = 30.1; 95% confidence limits (CL) 13.0-59.5) than in men (RR = 10.9; 95% CL 4.7-21.5), and showed a significant trend of greater risk with younger age at first treatment (P<0.001). The relative risk of solid cancers was similar between the sexes, but again significantly greater at young than at older ages of first treatment (P<0.01). Non-Hodgkin's lyrrphoma relative risks, although not related to sex or age, were significantly related to histology of the o;:iginal Hodgkin's disease, and were greatest after lymphocyte predominant Hodgkin's disease (RR = 55.6; 95% CL 18.0 -129.7). The relative risk of second cancers did not vary significantly according to whether or not splenectomy had been performed. Leukaemia risk was non-significantly greater after splenectomy than with no splenectomy, which accorded with previous evidence of a modest increased risk associated with this operation.If the greater relative risk of solid second cancers after treatment at young than at older ages persists with longer follow-up, the incidence rates of these second primaries in patients treated young for Hodgkin's disease will become very substantial as they age. This emphasises the need to maintain long-term follow-up surveillance of young Hodgkin's disease patients apparently cured of their disease, and to continue to develop new less carcinogenic treatment regimes.An increased risk of second cancers after modern intensive treatment for Hodgkin's disease is well established (Kaldor et al., 1987). After radiotherapy there are raised risks of several solid tumours (Boivin & O'Brien, 1988), and probably also of leukaemia (Boivin et al., 1984; Tucker et al., 1988;Van Leeuwen et al., 1989). After chemotherapy, a very high risk of acute or non-lymphocytic leukaemia has been shown (Pedersen-Bjergaard et al., 1987; Tucker et al., 1988), and in a recent study we found solid cancer risk also to be increased (Swerdlow et al., 1992). The risks of these second primary malignancies in relation to host factors, and subtype and stage of Hodgkin's disease, are unclear. Investigation of this needs data sets with large numbers of patients, and the results which have been published have been inconsistent (Tucker et al., 1988; Van der Velden et al., 1988;Kaldor et al., 1990;Henry-Amar et al., 1990). We present here analyses of these factors in data from the British National Lymphoma Investigation (BNLI), a long-established, large clinical collaborative investigation whose files have detailed treatment data and virtually complete follow-up information. Materials and methodsThe BNLI is a collaborative group of over 60 participating centres in the UK, which has collected detailed data on the diagnosis, therapy and follow-up of lymphoma patients treated at the centres since 1970. Most of the patients were in rand...

Second malignancy in patients with Hodgkin's disease treated at the Royal Marsden Hospital

“…The decrease in relative risk of second cancers overall with increasing age at first treatment accords with several previous reports (Glicksman et al, 1982;Sont et al, 1992;Abrahamsen et al, 1993;Swerdlow et al, 1993). For leukaemia, previous studies (Glicksman et al, 1982;van der Velden et al, 1988;Abrahamsen et al, 1993;Swerdlow et al, 1993) agree with the present analyses that relative risks diminish beyond middle age, and this has been the case in analyses where ANLL or AML were analysed separately (Glicksman et al, 1982;van der Velden et al, 1988), but results have been variable with regard to the trend in risks at younger ages of first treatment.…”

“…Careful clinical surveillance to detect breast cancers early is needed in women treated young with mantle radiotherapy. The only previous data on relative risks by age at first treatment for solid cancers more generally appear to be those from the BNLI (Swerdlow et al, 1993), which showed a significant trend of increasing relative risk with decreasing age (although less steep than in the present study) for non-lung solid cancers, and a nonsignificant trend in the same direction (except that no cases occurred under age 25) for lung cancer. The sole previous analyses by attained age appear to be those on breast cancer risk by Hancock et al (1993).…”

“…For leukaemia, previous studies (Glicksman et al, 1982;van der Velden et al, 1988;Abrahamsen et al, 1993;Swerdlow et al, 1993) agree with the present analyses that relative risks diminish beyond middle age, and this has been the case in analyses where ANLL or AML were analysed separately (Glicksman et al, 1982;van der Velden et al, 1988), but results have been variable with regard to the trend in risks at younger ages of first treatment.…”

Late effects of treatment for early-stage Hodgkin's disease

“…Although the AR increased with age, because malignancy is more common with increasing age, the relative risk of developing a second malignancy was greater in younger patients in this study, as has been reported by others (Henry-Amar, 1992;Swerdlow et al, 1992). Splenectomy has been reported as a risk factor for second malignancy in some studies (van Leeuwen et al, 1994) but not others (Valagussa et al, 1986;Swerdlow et al, 1993). The IDHD reported a relative risk of 1.3 for development of acute leukaemia (P < 0.05) and 1.4 for non-Hodgkin's lymphoma (P < 0.1).…”

High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin’s disease is unlikely to be associated with a major increased risk of secondary MDS/AML

“…Most of these studies have not included patients with uniform diagnoses and comparisons with similar patients not receiving high-dose therapy have not been made. This latter point is of great importance as secondary leukaemia is a well documented complication of standard dose chemotherapy for lymphoma, especially Hodgkin's disease (Tucker et al, 1988;Devereux et al, 1990;Swerdlow et al, 1993). A number of risk factors have been identified in the literature.…”