Sameer Sameer, N Prabhu, Kuppusamy Saranya, Adole Prashant S, Kayal Smita
Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND.
Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND.
Cureus. 2024 Feb 27;16(2):e55108. doi: 10.7759/cureus.55108. eCollection 2024 Feb.
Acute lymphoblastic leukemia (ALL) is a malignant uncontrolled overproduction of immature lymphoid cells in blood and bone marrow. The primary treatment of ALL is chemotherapy. Chemotherapy can have myriad systemic side effects, notably cardiovascular derangement. Autonomic derangement occurrence in cancer patients signifies cardiovascular risk in them and is a determinant of cardiovascular morbidity and mortality. Elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) levels implicated in the regulation of inflammation indicate endothelial dysfunction. High levels of high-sensitivity C-reactive protein (hsCRP) can be indicative of low-grade inflammation. Hence, in this study the cardiac autonomic function and endothelial and inflammatory biomarker levels in adult patients with ALL were assessed immediately and three months after chemotherapy.
In this longitudinal study, 30 ALL patients (23 males, seven females) aged between 18 to 50 years, who had completed chemotherapy regimens, and 30 age and gender-matched healthy participants (controls) were recruited. Cardiac autonomic function tests (short-term heart rate variability (HRV), 30:15 ratio, synaptic excitation and inhibition (E/I) ratio, diastolic blood pressure (DBP) response to isometric hand grip), endothelial markers (sVCAM-1 and sICAM-1), and inflammatory marker (hsCRP) were assessed immediately and at three months after chemotherapy.
Magnitudes of time domain and frequency domain indices, conventional autonomic function test indices, and biomarkers were deranged in ALL patients immediately after chemotherapy. After three months, cardiac autonomic function parameters were found to improve in the form of increased root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of the interbeat intervals of normal sinus beats (SDNN), total power, high-frequency (HF)nu, and decreased low-frequency(LF)nu & LF-HF ratio. Endothelial (sVCAM-1) and inflammatory markers (hsCRP) were lower in the patient group as compared to the controls immediately after chemotherapy. Three months after chemotherapy, the levels of endothelial and inflammatory markers did not show much change.
In this study, we found ALL patients showed higher sympathetic drive, decreased parasympathetic modulation, and sympathovagal imbalance immediately after chemotherapy as compared to the controls, indicating cardiovascular risk. After three months, improvement in cardiovascular autonomic function was observed. ALL itself is a state of inflammation with elevated endothelial and inflammatory markers; thus, the decreased endothelial and inflammatory markers could be attributed to the immediate effect of chemotherapy.
急性淋巴细胞白血病（ALL）是一种血液和骨髓中未成熟淋巴细胞恶性失控过度增殖的疾病。ALL的主要治疗方法是化疗。化疗会产生众多全身副作用，尤其是心血管紊乱。癌症患者出现自主神经紊乱表明他们存在心血管风险，并且是心血管发病和死亡的一个决定因素。可溶性血管细胞黏附分子-1（sVCAM-1）和可溶性细胞间黏附分子-1（sICAM-1）水平升高与炎症调节有关，提示内皮功能障碍。高敏C反应蛋白（hsCRP）水平升高可表明存在低度炎症。因此，在本研究中，对成年ALL患者化疗后即刻及化疗后三个月的心脏自主神经功能以及内皮和炎症生物标志物水平进行了评估。
在这项纵向研究中，招募了30名年龄在18至50岁之间、已完成化疗方案的ALL患者（23名男性，7名女性）以及30名年龄和性别匹配的健康参与者（对照组）。在化疗后即刻及化疗后三个月评估心脏自主神经功能测试（短期心率变异性（HRV）、30:15比值、交感神经兴奋和抑制（E/I）比值、等长握力时的舒张压（DBP）反应）、内皮标志物（sVCAM-1和sICAM-1）以及炎症标志物（hsCRP）。
化疗后即刻，ALL患者的时域和频域指标、传统自主神经功能测试指标以及生物标志物均出现紊乱。三个月后，发现心脏自主神经功能参数有所改善，表现为正常心跳间连续差值的均方根（RMSSD）、正常窦性心律搏动间期的标准差（SDNN）、总功率、高频（HF）nu增加，低频（LF）nu及LF-HF比值降低。化疗后即刻，患者组的内皮标志物（sVCAM-1）和炎症标志物（hsCRP）低于对照组。化疗三个月后，内皮和炎症标志物水平变化不大。
在本研究中，我们发现与对照组相比，ALL患者化疗后即刻表现出更高的交感神经驱动、副交感神经调节降低以及交感迷走神经失衡，提示存在心血管风险。三个月后，观察到心血管自主神经功能有所改善。ALL本身是一种内皮和炎症标志物升高的炎症状态；因此，内皮和炎症标志物降低可能归因于化疗的即刻效应。
