Jarfelt M, Kujacic V, Holmgren D, Bjarnason R, Lannering B
Department of Pediatrics, Division of Haematology and Oncology, Cardiovascular Institute, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Pediatr Blood Cancer. 2007 Nov;49(6):835-40. doi: 10.1002/pbc.21289.
Anthracyclines (AC) have contributed significantly to increased survival rate in acute lymphoblastic leukemia (ALL), although the use of these drugs is limited due to cardiotoxicity. The aim was to evaluate heart muscle function in asymptomatic adult survivors of ALL treated in early childhood in relation to the combined effects of AC and other potential cardiotoxic factors.
Twenty-three young adult ALL survivors who had all received treatment with median 120 (120-400) mg AC/m(2) before the onset of puberty were examined median 21 years after remission and compared with 12 healthy controls. Basal echocardiography including two-dimensional (2D) M-mode and Doppler examination was performed, followed by a maximal exercise stress test and stress echocardiography immediately after stress test and after 5 min recovery.
We found significant differences in systolic function between patients and controls at maximal exercise despite absence of reported symptoms from the patients. The most marked difference was in ejection fraction at stress 59.5% (32.6-81.1) and 77.3% (66.2-85.3), respectively (P < 0.00006). Ten out of 23 patients reduced their ejection fraction at stress compared with at rest; this was not found in any of the controls. Cardiovascular risk factors such as GH deficiency and a high proportion of trunk fat did not have an impact on cardiac function.
With very long follow up in a homogenous cohort of ALL survivors, we found subclinical cardiac dysfunction with exercise stress echocardiography even after low doses of AC.
蒽环类药物(AC)对提高急性淋巴细胞白血病(ALL)的生存率有显著贡献,尽管由于心脏毒性,这些药物的使用受到限制。本研究旨在评估儿童期早期接受治疗的无症状ALL成年幸存者的心肌功能,以探讨AC与其他潜在心脏毒性因素的联合作用。
23名年轻的ALL成年幸存者在青春期前均接受了中位剂量为120(120 - 400)mg AC/m²的治疗,在缓解后中位21年接受检查,并与12名健康对照者进行比较。进行了包括二维(2D)M型和多普勒检查的基础超声心动图检查,随后进行最大运动负荷试验以及负荷试验后立即和恢复5分钟后的负荷超声心动图检查。
尽管患者未报告有症状,但我们发现患者与对照组在最大运动时的收缩功能存在显著差异。最明显的差异在于负荷时的射血分数,患者组为59.5%(32.6 - 81.1),对照组为77.3%(66.2 - 85.3)(P < 0.00006)。23名患者中有10名在负荷时的射血分数较静息时降低,而对照组中未发现这种情况。生长激素缺乏和躯干脂肪比例高等心血管危险因素对心脏功能没有影响。
在一组同质的ALL幸存者中进行了非常长期的随访,我们发现即使在低剂量AC治疗后,运动负荷超声心动图检查仍显示有亚临床心脏功能障碍。