Identifying Pediatric Patients with Sickle Cell Disease at High Risk of Experiencing Chronic Pain after HSCT

Introduction: Currently, hematopoietic stem cell transplantation (HSCT) stands at the forefront of curative therapies for sickle cell disease (SCD), significantly improving the quality of life for patients. Unfortunately, chronic pain remains a burden for many sickle cell patients, leading to frequent emergency department visits, costly medication use, lengthy hospitalizations, and the need for expensive diagnostic tests. While HSCT can often alleviate the need for opioids, there remains a subset of patients who continue to suffer from chronic pain post-HSCT¹. Studies have shown that a variety of genetic and environmental factors, including trauma, infection, and emotional stress, can contribute to this ongoing pain^2-4.

To ensure optimal outcomes post-HSCT, our institution thoroughly explores several areas prior to the procedure including cardiac health, psychosocial circumstances and respiratory health. However, we have identified a variability among patients with SCD particularly those with chronic pain who are at higher risk of experiencing pain during and after the HSCT with increased severity. This results in longer hospital stays and poorer pain control during and after hospitalization. Our goal is to streamline care for these pediatric patients and optimize pain control during hospitalization, thus reducing the length of hospitalization.

To achieve this goal, we aim to create a checklist in partnership with our referring institutions to identify patients who are more likely to suffer from chronic pain prior to HSCT hospitalization. By identifying and addressing pain-prone phenotypes and risk factors pre-HSCT, we aim to improve outcomes and ensure the best possible care for these vulnerable patients.

Methods: This was an IRB-approved retrospective medical record review of 89 subjects who underwent HSCT for SCD, ages 0-21 years of age, at Childrens National Hospital between 10/10/1996-3/31/2023. We performed multiple generalized linear regression analysis to identify and quantify risk factors associated with the risk of developing chronic pain after HSCT, the risk of requiring physical therapy (PT) after HSCT and the changes in the post-HSCT pain score using R version 4.3.1.

Results: Patients with a pre-HSCT pain score of 0 have lower odds of chronic pain post-HSCT compared to those with a pre-HSCT pain score > 0 (OR = 0.1 (0.0,0.6), p value = 0.02). Patients with any psychiatric diagnosis (depression, anxiety, and/or ADHD) have higher odds of chronic pain post-HSCT compared to those without (OR = 22.0 (1.7,645.8), p value = 0.03). Patients with a matched related donor (MRD) donor type have lower odds of requiring PT post-HSCT (OR = 0.1 (0.0,0.2), p value = <0.01). Patients who had one pain admission per year preceding HSCT, have a rate ratio of 1.7 (1.0,2.9), in comparison to those without any painadmissions, for having post-HSCT pain scores > 0 (p value = 0.4). Patients who had two or more pain admissions per year preceding HSCT have a rate ratio of 2.1 (1.4,3.2) for having post-HSCT pain scores >0 (p value <0.01) when compared to patients without pain admission preceding HSCT. For every one unit increase in the pre-pain score of the patient, the odds of maximum pain score > 0 increases by 230% (p value = 0.03). For every one year increase in the patient's age, the odds of post-HSCT pain score being greater than 0 increased by 12%, with a confidence interval from 0% to 28% (p value = 0.1).

Conclusions:

Based on our study of pediatric patients with SCD undergoing HSCT, several key findings emerged. Patients with no pre-HSCT pain score had significantly lower odds of chronic pain post-HSCT compared to those with a pre-existing pain score>0. Conversely, psychiatric diagnoses increased the likelihood of chronic pain post-HSCT, with notably higher odds observed for patients with depression, anxiety, or ADHD. Having a MRD was associated with reduced odds of needing physical therapy post-HSCT. Patients with a history of frequent pain admissions prior to HSCT also had higher rates of post-HSCT pain. Additionally, older age slightly increased the likelihood of post-HSCT pain. These findings underscore the importance of assessing and managing pre-HSCT pain levels, addressing psychiatric comorbidities, and tailoring interventions based on donor type and patient age to optimize pain management and recovery outcomes in pediatric HSCT recipients with SCD.