To the Editor:

There has been a rapid global response in vaccine development since declaration of the COVID-19 pandemic in March 2020. Data are beginning to emerge establishing the safety, tolerability, immunogenicity and efficacy of COVID-19 vaccines in children and adolescents.^{1, 2} While children and adolescents infected with SARS-CoV-2 suffer from milder illness than adults, those with underlying health co-morbidities, including cancer, can suffer from severe disease.^{3, 4} Minimizing risk of exposure remains important in reducing the risk of SARS-CoV-2 infection in children with cancer,⁵ however vaccination is emerging as a critical strategy for prevention of infection, reducing severity of disease and contributing to herd immunity.

Currently, there is widespread recommendation for patients with cancer to receive COVID-19 vaccination,⁶ supported by a prospective observational study in adults with cancer that identified safety and immunogenicity following BNT162b2 vaccination.⁷ Although inferior to healthy controls, rates of seroconversion were better following an early second vaccine boost on day 21 and for patients with solid tumors compared to those with hematological cancers. The latter is supported by a recent study, which identified a blunted and heterogeneous antibody response to BNT162b2 vaccination in adults with hematological malignancies.⁸

There is a paucity of data regarding COVID-19 vaccination in children with cancer; however, these findings have been mirrored by studies of inactivated influenza and pneumococcal vaccination, which reflect that children with cancer are able to mount protective immune responses to vaccination, and that the extent of response is modulated by a variety of factors that can include the number of doses received, whether treatment is being delivered for a solid or hematological malignancy and lymphocyte count at the time of vaccination.^9-11 Given that the patterns of response are reflective of host immunity, similar outcomes are likely to be found following COVID-19 vaccination in children with cancer, suggesting that optimization of outcome could be achieved by timing immunization at the furthest point from the immunosuppressing effect of cytotoxic treatment during a given cycle. In addition, a specific consideration to vaccination of children with acute lymphoblastic leukemia is the presence of polyethylene glycol (PEG) as a stabilizing component of mRNA COVID-19 vaccines, necessitating the development and validation of strategies to mitigate risk for children with a prior history of hypersensitivity to PEG-asparaginase.¹²

The COVID-19 and Cancer Taskforce have identified that on an international scale, there has been little planning for the systematic collection of data from patients with cancer receiving COVID-19 vaccines.¹³ As COVID-19 vaccines become licensed for use in children and adolescents, there is a need to develop clinical trials in children with cancer to provide best evidence. However, given that access to trials will not be universal and the length of time required to conduct a trial, it will be essential for global collation of data for children with cancer who are vaccinated outside of a clinical trial setting. This should include a minimum clinical dataset, with reporting of safety data, including adverse events such as myocarditis and pericarditis,¹⁴ and history of COVID-19 infection prior to and postvaccination. This could be best facilitated by platforms such as the Global COVID-19 Observatory and Resource Center for Childhood Cancer, which continues to provide an invaluable resource on COVID-19 for health care professionals treating children withcancer.³

致编辑：

自 2020 年 3 月宣布 COVID-19 大流行以来，全球对疫苗开发做出了迅速反应。数据开始出现，确定 COVID-19 疫苗在儿童和青少年中的安全性、耐受性、免疫原性和有效性。^{1, 2}虽然感染 SARS-CoV-2 的儿童和青少年的病情较成人轻，但患有包括癌症在内的潜在健康并发症的儿童和青少年可能会患上严重的疾病。^{3, 4}最大限度地降低接触风险对于降低癌症儿童感染 SARS-CoV-2 的风险仍然很重要，⁵然而，疫苗接种正在成为预防感染、降低疾病严重程度和促进群体免疫的关键策略。

目前，普遍建议癌症患者接种 COVID-19，6^得到一项针对癌症成人的前瞻性观察研究的支持，该研究确定了 BNT162b2 疫苗接种后的安全性和免疫原性。⁷虽然不如健康对照组，但在第 21 天早期进行第二次疫苗加强后，与患有血液系统癌症的患者相比，实体瘤患者的血清转化率更高。后者得到了最近一项研究的支持，该研究确定了患有血液系统恶性肿瘤的成人对 BNT162b2 疫苗接种的抗体反应迟钝和异质。⁸

缺乏关于癌症儿童 COVID-19 疫苗接种的数据；然而，这些发现在灭活流感和肺炎球菌疫苗的研究中得到了反映，这反映了患有癌症的儿童能够对疫苗接种产生保护性免疫反应，并且反应程度受多种因素的调节，包括数量接受的剂量，无论是针对实体瘤还是恶性血液病进行治疗，以及接种疫苗时的淋巴细胞计数。^9-11鉴于反应模式反映了宿主免疫，在癌症儿童接种 COVID-19 疫苗后可能会发现类似的结果，这表明可以通过在距离细胞毒的免疫抑制作用最远的点进行定时免疫来优化结果在给定的周期内进行治疗。此外，对患有急性淋巴细胞白血病的儿童进行疫苗接种的一个具体考虑是聚乙二醇 (PEG) 作为 mRNA COVID-19 疫苗的稳定成分的存在，因此需要制定和验证降低既往病史儿童风险的策略对 PEG-天冬酰胺酶过敏。¹²

COVID-19 和癌症工作组已经确定，在国际范围内，几乎没有计划系统地收集接受 COVID-19 疫苗的癌症患者的数据。¹³随着 COVID-19 疫苗获准用于儿童和青少年，有必要在患有癌症的儿童中开展临床试验以提供最佳证据。然而，鉴于获得试验的机会并不普遍，并且进行试验所需的时间很长，因此对于在临床试验环境之外接种疫苗的癌症儿童的数据进行全球整理至关重要。这应包括一个最低限度的临床数据集，并报告安全性数据，包括心肌炎和心包炎等不良事件，¹⁴以及接种疫苗前后的 COVID-19 感染史。全球 COVID-19 观察站和儿童癌症资源中心等平台可以最好地促进这一点，该中心继续为治疗儿童癌症的医疗保健专业人员提供有关 COVID-19 的宝贵资源。³