In the United States, cancer is a significant challenge for children, being the second-leading cause of death for those aged 1 to 14 years.1 Leukemia is the second-leading cause of cancer-related death among children and young adults younger than 20 years, accounting for 24.7% of all cancer-related mortalities.2 However, there is a powerful story of hope and resilience behind these numbers. Despite the daunting statistic that 1 in 257 children will be diagnosed with cancer before they turn 20, advancements in medical treatments and supportive care have dramatically improved survival rates.1
For example, for more than 50 years, pediatric acute lymphoblastic leukemia (ALL) has shown steady outcome improvements, ranging from a 3-year survival in 1975 of ∼59% and a 5-year survival in 2020 of ∼90%.3 Indeed, multidrug chemotherapy-based regimens and various forms of supportive care have rendered all forms of ALL (B-cell [B-ALL] and T-cell [T-ALL] immunophenotypes) treatable. But the emergence of side effects associated with usual care can substantially impact patient quality of life.
Chemotherapy-resistant diseases and adverse effects, such as myelosuppression and secondary malignancies, highlight the importance of developing more effective and less harmful treatment options, along with supportive, individualized care plans that optimize treatment and manage side effects as well as long-term sequelae.4
Treatment for ALL, the most prevalent type of childhood cancer, is typically divided into remission induction, consolidation/intensification, and maintenance phases. It is also guided by prognostic factors and minimal residual disease (MRD) monitoring to tailor treatment intensity and improve outcomes.5-7 Prognostic factors, such as age at diagnosis, initial white blood cell count, ALL subtype, sex, chromosomal abnormalities, and response to initial treatment, help determine treatment intensity.6,7 In addition, MRD monitoring is crucial for assessing treatment effectiveness and relapse risk, with recent advancements such as the ALLIUM tool enhancing risk stratification.7
Overall, intensification of treatment for the population at high risk of a relapse and the avoidance of treatment-related toxicity in the low-risk population are guiding principles informed by landmark clinical trials.8 Although definitions for relapse or remission were not standardized across clinical trials, it appears that ALL returns in approximately 15% of young patients.9,10 One study emphasized that cranial radiotherapy for pediatric patients with T-ALL and central nervous system (CNS) relapse had limited benefit.11 Although radiation-free, contemporary, optimized chemotherapy-based regimens can provide excellent control of systemic and CNS leukemia, it can also be neurotoxic in ≤12% of pediatric ALL cases. These side effects can be as varied as the inciting agents.12 Another treatment for pediatric patients with high-risk or relapsed ALL, allogeneic hematopoietic stem cell transplantation (HSCT), remains a crucial treatment option, but it is associated with more side effects than chemotherapy and immunotherapy.13
Plateauing survival rates and the dismal outcomes for pediatric patients with relapsed or refractory ALL (survival rates are ~50% in B-ALL, and often <20% in T-ALL) compel the search for novel therapies.14 Targeted therapies, including tyrosine kinase inhibitors (TKIs), CAR T-cell therapies, and antibody–drug conjugates (ADCs), hold promise as next-generation agents that can overcome some of the limitations of standard care. A landmark trial involving a TKI, imatinib mesylate, showed that its addition to intensive chemotherapy resulted in outcomes similar to those achieved with HSCT in pediatric patients with Philadelphia chromosome–positive ALL.14 Furthermore, the global phase 2 ELIANA trial (ClinicalTrials.gov identifier NCT02435849) showed that CAR T-cell therapy with tisagenlecleucel achieved an overall remission rate of 81% in pediatric and young adult patients with relapsed/refractory B-ALL, with 59% of responders remaining relapse-free at 12 months.15 Two other randomized controlled trials confirmed the benefit of the bispecific T-cell engager immunotherapy, blinatumomab, in pediatric patients with high-risk first relapse of B-ALL with chemotherapy-responsive disease, and the findings suggest that blinatumomab provides a more effective and potentially less hazardous treatment.16,17 In addition, studies on inotuzumab ozogamicin, an ADC, have shown promising outcomes. A phase 2 study reported an overall response rate (ORR) of 81.5% in pediatric patients with relapsed or refractory B-ALL, with 81.8% achieving MRD negativity. Another study by the Children’s Oncology Group (COG) found an ORR of 58.3% in heavily pretreated patients.14
Targeted therapies have the potential to revolutionize care and replace some standard treatments. However, they are not without their own toxicities, necessitating the development of personalized survivorship care plans (SCPs) that consider pediatric patient and/or family/caregiver perspectives.
More than 90% of pediatric patients with ALL are cured, but 20% will develop at least 1 chronic health condition 20 to 25 years after diagnosis.18,19 The severity of these effects will depend on, among other factors, the type and duration of treatment, gender, the age at treatment, and overall health. Long-term effects are issues that persist after treatment, such as infertility and fatigue, whereas later effects, like heart disease or secondary cancers, may not appear until years later.20 That is why contemporary antileukemic regimens seek to stratify treatment more optimally, reserving more intensive and toxic treatment for those children who need it most, while avoiding it in those with a good prognosis.18,19
Nevertheless, for 1 out of every 4 child, adolescent, and young adult cancer survivors, therapy-related complications will be severe or life-threatening.21 Fortunately, several collaborative groups, including the COG, the Pan-European Network for Care of Survivors, and the International Guideline Harmonization Group, have developed guidelines for long-term follow-up.
The COG Long-Term Follow-Up Guidelines, first developed in 2003 and updated every 5 years, provide risk-based, exposure-related clinical practice guidelines for screening and managing late effects. The latest version (6.0), released in October 2023, focuses on survivors who have completed cancer therapy for 2 or more years. It includes recommendations for periodic evaluation, health counseling, and early identification of late effects. The guidelines are based on 165 therapeutic exposures, detailing specific chemotherapy agents, doses, and radiotherapy sites. It also includes recommendations for long-term surveillance posttreatment with targeted therapies such as TKIs.22,23 Although cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and abnormal liver function tests are some of the known toxicities associated with immunotherapies, their associations with long-term or late effects among pediatric cancer survivors will likely be included in future guidelines as more information becomes available.24,25
Approximately 1 in 530 US adults between the ages of 20 and 39 years are survivors of childhood cancer. Their quality of life and those of others who have experienced pediatric cancer is contingent on effective survivorship care, which presumes a patient’s knowledge of their own diagnosis and treatment. But many survivors were treated at a young age, which means that they may only have vague recollections about treatment details. Some may also suffer from neurocognitive impairments related to treatment or have psychological trauma impacting their recollections of treatment.26-28 In addition, only 35% of adult survivors of childhood cancer understood that posttreatment serious health issues were related to curative regimens given earlier in life.29
SCPs bridge the gap between lack of survivor knowledge of need for survivorship care and transition from treatment to posttreatment. The Passport of Care is a web-based communication tool between survivors, specialist, and primary-care healthcare professionals and is meant for clinicians taking care of survivors at COG-affiliated clinics. This individualized SCP contains a treatment summary, potential late effects, associated risk factors, and screening recommendations. The Figure provides considerations for setting up a pediatric SCP.21,26,27
Compared with younger counterparts, older patients (>18 years) have also been found to carry wallet-sized SCP cards at a greater frequency and have more confidence in understanding its content.29 Additionally, families feel positive about SCPs and believe that they provide important information on healthcare after cancer. Features enabling the updating of SCPs may also reverse waning interest from families with the passage of time.30
Nurses often dedicate a significant amount of time as the primary personnel responsible for inputting SCP content.31 They have to monitor survivors’ health and coordinate care among various healthcare professionals to ensure continuity and comprehensiveness in follow-up.32
Furthermore, as health educators, they provide essential information to survivors and families about potential late effects of treatment and ongoing health management.33 However, as the focus of most SCPs remains on acute treatment phases, long-term survivorship needs remain inadequately addressed. Together with the evolving landscape of pediatric cancer care, there remains a need for ongoing adaptation and training of these healthcare professionals to meet the complex needs of survivors effectively.
In conclusion, while advancements in pediatric oncology have significantly improved survival rates for the most common childhood cancer, ALL, the long-term and late effects of treatment continue to pose substantial risks to survivors’ quality of life. The integration of targeted therapies and immunotherapies offers promising avenues to enhance treatment efficacy and mitigate adverse effects.
Once cured, the transition to life after treatment for childhood cancer survivors is not without health-related perils, some of which may not be known to them. Comprehensive SCPs are essential in bridging the gap between survivors’ lack of knowledge about the need for ongoing care and ensuring effective management of long-term health issues. Collaborative guidelines provide a framework for risk-based, exposure-related follow-up care, emphasizing early identification and management of late effects.
Nurses and healthcare professionals play a critical role in implementing and updating SCPs, ensuring continuity and comprehensiveness in follow-up care. As pediatric oncology evolves, so must the strategies for long-term care, necessitating ongoing adaptation and training of healthcare professionals to meet the complex needs of survivors. Shifting the focus from merely achieving remission to ensuring long-term health and quality of life for childhood cancer survivors is essential in future-proofing pediatric oncology and supporting the well-being of survivors throughout their lives.
Zeena Nackerdien, PhD, is a scientist and medical writer at Montefiore Medical Center’s Department of Nursing in Bronx, NY.
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