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• W3036355966 abstract "The evidence that all-trans retinoic acid (ATRA) is highly effective in the induction of blast differentiation and its subsequent use in clinical practice induced a dramatic improvement in the outcome of acute promyelocytic leukaemia (APL), especially when associated with standard chemotherapy.1, 2 Further advances have been made in the treatment of this disease with more recent arsenic trioxide (ATO)-based regimens.3, 4 To illustrate, a recent update of the APL0406 Italian–German randomized trial showed that disease free survival at 72 months was 96·6% and 79·8% for patients treated with ATRA–ATO and ATRA chemotherapy, respectively.5 Given the notable therapeutic advances in this area, the number of APL survivors has substantially increased in recent years.6 However, little is known about the late effects of treatments and impact on patients’ health-related quality of life (HRQOL). We aimed to examine long-term functional aspects and symptom burden, by age at diagnosis (<30 vs. ≥30 years) in APL patients. This age cut-off was based on previous AML studies indicating better clinical outcomes for younger patients compared to their older counterparts.7 We also investigated whether the impact of comorbidities on HRQOL outcomes varies by age at diagnosis. Analysis is based on 244 adult APL patients previously treated with ATRA plus chemotherapy with a median time from diagnosis of 14·3 years, who were originally enrolled in two clinical trials by the Italian Group for Adult Haematological Diseases (GIMEMA), i.e. AIDA 2000 and AIDA 0493; details on study sample and long-term generic HRQOL outcomes have been previously reported.8 The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 module (EORTC QLQ-C30)9 and the Self-administered Comorbidity Questionnaire (SCQ)10 instruments were used. For each EORTC QLQ-C30 scale, we estimated the adjusted mean differences between younger and older APL survivors as the coefficient of a binary indicator indicating patient's age at diagnosis (older vs. younger), in a linear regression model including the following key confounders: sex, number of comorbidities (<2 vs. ≥2), education (low vs. higher), living arrangements (living alone vs. living with someone) and risk at diagnosis (low/intermediate vs. high). We also assessed HRQOL clinical relevance using previously published thresholds.11 The majority of patients (51·4%) were intermediate risk at the time of diagnosis, with a prevalence of female sex (52·9%). Median age at diagnosis was 23 years (range: 5–29 years) and 44 years (range: 30–75 years) for younger and older APL survivors, respectively. Table I reports adjusted mean score differences of the EORTC QLQ-C30 scales of patients by age at diagnosis (<30 vs. ≥30 years) defined, for the purpose of this work, as younger (n = 59) and older APL survivors (n = 185). The largest difference, both statistically and clinically relevant, was found for cognitive functioning (a mean score difference of −8·53, P = 0·002), and favoured younger patients. No other statistically significant differences were found between groups. Figure 1 depicts functional and global QoL scales (Fig 1A) as well as symptoms (Fig 1B) by age group categories. The differences in means scores between patients with low versus high comorbidity burden varied by age and were generally larger in older APL survivors. The largest difference was found for the global QoL scale. In younger APL patients, the mean score difference between those with low and high comorbidity burden was Δ = 7·6. Conversely, in older APL survivors, the mean global QoL score difference between those with low or high comorbidity burden was Δ = 14·9. Further results are reported in Fig 1. We observed that, even when adjusting for key potential confounders, younger APL survivors reported better cognitive functioning than older patients. A recent large European study,12 using the EORTC QLQ-C30 questionnaire in the general population, found worse cognitive functioning in younger versus older individuals, therefore providing support that our finding of a better cognitive functioning in younger APL survivors does not reflect differences typically seen in the general population. The presence of cognitive deficits in cancer survivors has recently been highlighted as a major issue deserving more attention by the scientific community; however, most of the empirical evidence in this area stem from studies conducted in patients with solid tumours.13 Indeed, in 2016 a review by Williams et al.14 on chemotherapy-related cognitive impairments in patients with haematological malignancies found very few studies, none of which reported empirical data for APL patients. As compared to the other subtypes of AML, the median age of appearance of APL is usually low. Our results seem to corroborate the importance of the age cut-off used by Pemmaraju et al.7: 51% of patients out of 3 922 adult AML patients were APL with a better outcome compared to older patients. Our analysis also indicates that the impact of comorbidities may be generally lower in younger patients, in particular with regard to global health status/QoL. Longitudinal follow-up of APL patients after standard chemotherapy is usually performed for 48 months after the end of maintenance therapy and our results emphasize the need to prolong the clinical follow-up while discontinuing the molecular evaluation of residual disease. Our study has limitations inherent to its cross-sectional design and also, we observe that a more in-depth evaluation of cognitive functioning using other measures or batteries of neuropsychological tests could have provided further insights. In conclusion, our data suggest that APL patients diagnosed at an earlier age (i.e. <30 years) report better long-term cognitive functioning than those diagnosed at 30 years or older. Further research is needed to better understand the role of age at the time of APL diagnosis in determining long-term patient outcomes. EB: Consultancy: Amgen, Celgene, outside the submitted work. MB: Honoraria by Novartis, Pfizer, Incyte, Celgene, outside the submitted work. FE: personal fees from Bristol-Myers Squibb, Amgen, Orsenix, Incyte and Takeda; grants from Amgen, outside the submitted work. FR: Advisory Board: Amgen, Novartis and Argenx; institutional fees from Amgen and Novartis, outside the submitted work. ML: Travel grant: Gilead sci; Advisory Boards: Novartis, Gilead sci, MSD, Sanofi, Daiichi Sankyo, Abbvie, outside the submitted work. MV: personal fees from Jazz Healthcare Italy SRL, Amgen, Millennium Pharmaceuticals Inc., Celgene, Janssen, Novartis and Incyte, outside the submitted work. MB and FE designed the study and wrote the manuscript. FC, performed statistical analysis. All authors interpreted the data, read, commented on, and approved the final version of the manuscript." @default.
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• W3036355966 date "2020-06-18" @default.
• W3036355966 modified "2023-10-18" @default.
• W3036355966 title "Younger age at diagnosis of acute promyelocytic leukaemia is associated with better long‐term cognitive functioning" @default.
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• W3036355966 doi "https://doi.org/10.1111/bjh.16877" @default.
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