Total late effect burden in long-term lymphoma survivors after high-dose therapy with autologous stem-cell transplant and its effect on health-related quality of life

Abstract

Lymphoma survivors after high-dose therapy with autologous stem-cell transplant (HDT-ASCT) are at risk of several late effects, which might impair their health-related quality of life (HRQoL). We assessed the total late effect burden in this population, and how it affects HRQoL. All lymphoma survivors treated with HDT-ASCT as adults in Norway between 1987 and 2008 were identified, and 271 (68%) attended both a comprehensive clinical assessment and completed a questionnaire. Severity of 45 conditions in 12 organ-system categories were graded as mild, moderate, severe or life-threatening, according to a modified version of CTCAEv4.03. At a median of 8 years after HDT-ASCT, 98% of survivors had at least one moderate or more severe late effect and 56% had severe or life-threatening late effects. Fourteen percent had low, 39% medium and 47% high late effect burden, defined as having moderate or more severe late effects in 0-1, 2-3 and >3 organsystems, respectively. Female sex, increasing age, B-symptoms at diagnosis and >1 treatment line prior to HDT-ASCT were independently associated with having high late effect burden. The survivors had significantly poorer physical and mental HRQoL assessed by the Short Form-36 compared to age- and sex-matched controls. The prevalence of poor physical and mental HRQoL increased with higher late effect burden (both P<0.001), and the low burden group had better physical HRQoL than controls (P<0.001). In conclusion, lymphoma survivors after HDT-ASCT have impaired HRQoL, seemingly driven by a high late effect burden. This highlights the importance of prevention, regular assessments for early detection and treatment of late effects and modifiable risk factors.

Figure 1.

Maximum grade late effect per survivor for each organ-system category and for any organ system. Blue: grade 1 (mild/asymptomatic), green: grade 2 (moderate), orange: grade 3 (severe), red: grade 4 (life-threatening)

Figure 2.

Number of organ-system categories with grade 2 or higher late effects per survivor. Green (0-1 organ system): low late effect burden (n=37); orange (2-3 organ systems): medium late effect burden (n=105); red (>3 organ systems): high late effect burden (n=129).

Figure 3.

Health-related quality of life and its association with late effect burden. (A) Mean physical composite scale (PCS) scores. (B) Percentage with poor physical health-related quality of life (HRQoL) (PCS score <40). (C) Mean mental composite scale (MCS) scores. (D) Percentage with poor mental HRQoL (MCS score <40), (E) Mean Short Form-36 domain scores for controls (gray) compared with all survivors (blue) and survivors with low late effect burden (green): grade 2 or more severe late effects in 0-1 organ-system categories, medium late effect burden (orange): grade 2 or more severe late effects in 2-3 organ-systems and high late effect burden (red): grade 2 or more severe late effects in >3 organ systems. PF: physical functioning; RP: role physical; BP: bodily pain; GH: general health; SF: social functioning; VT: vitality; RE: role emotional; MH: mental health, PCS: physical composite score, MCS: mental composite score. Statistically significant differences compared to controls denoted as *P<0.05, **P<0.01 and ***P<0.001.