Pain and opioid use after reversal of sickle cell disease following HLA-matched sibling haematopoietic stem cell transplant
The burden of pain varies among patients with sickle cell disease (SCD). Chronic pain, resulting from multiple aetiologies, is common in SCD. The Analgesic, Anaesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (ACTTION-AAPT) criteria have recently described subcategories of chronic SCD pain (Dampier et al, 2017). Haematopoietic stem cell transplant (HSCT) is the most accessible curative therapy for SCD resulting in disease-free survival in over 85% (Hsieh et al, 2014; Gluckman et al, 2017). After successful HSCT (as defined by haematological parameters), most patients are weaned off opioids; however, a subgroup of patients continues to experience pain that requires opioid treatment.
We determined the prevalence and correlates of pain requiring continued opioid treatment at 12 months after successful non-myeloablative human leucocyte antigen-matched sibling allogeneic HSCT in a cohort of SCD patients (Fig 1) (Hsieh et al, 2014). The Institutional Review Board of the National Institutes of Health approved the protocol. All participants provided informed consent. Detailed data on the clinical course, pain, opioid use and laboratory values were prospectively collected within 3 months prior to HSCT and at 12 months post-HSCT (n = 35). Patient Reported Outcomes Measurement Information System (PROMIS) measures were also prospectively collected at the same time points in a subgroup of these patients (n = 20). The PROMIS domains assessed included pain intensity, pain impact, anxiety, depression, satisfaction with social role, physical function, fatigue and sleep disturbance (Cella et al, 2007; Keller et al, 2017). All PROMIS raw data were converted to T-scores.
Opioid use pre- and post-HSCT by AAPT pain categories. *3 patients in acute episodic pain group had not reported using opioids. **1 patient in acute episodic pain group was on long acting opioids intermittently. AAPT, ACTTION-American Pain Society Pain Taxonomy diagnostic criteria for chronic SCD pain; AAPT subtype 1, Chronic SCD pain without contributory disease complications was used if there was no evidence of contributory SCD complications based on either clinical signs (e.g., presence of leg ulcers) or test results (e.g., imaging abnormalities); AAPT subtype 2, Chronic SCD pain with contributory disease complications was used if there was evidence of contributory SCD complications based on clinical signs or test results; AAPT subtype 3, Chronic SCD pain with mixed pain types was used if there was evidence of contributory SCD complications (e.g., avascular necrosis) based on clinical signs or test results and there was also pain occurring in unrelated sites (e.g., arms, back, chest, or abdominal pain); HSCT, hematopoietic stem cell transplant; LA Opioids, Long acting opioids; SA Opioids, Short acting opioids; SCD, sickle cell disease.
Based on pain history pre-HSCT, patients reporting chronic pain were classified using AAPT guidelines (Dampier et al, 2017) into one of following three chronic pain subtypes: (i) AAPT subtype 1 – chronic pain without contributory SCD complications (e.g. avascular necrosis or leg ulcers), (ii) AAPT subtype 2 – chronic pain with evidence of contributory SCD complications based on clinical signs or test results (iii) AAPT subtype 3 – chronic pain with mixed pain types if there was evidence of contributory SCD complications and also pain in unrelated sites (e.g. arms, back, chest or abdominal pain). Patients who only experienced acute episodic pain were grouped separately (Episodic pain only) (Fig 1). Non-parametric statistical analysis was performed using IBM SPSS Statistics (IBM Corp. Released 2013. IBM SPSS Statistics for windows, version 24 0. Armonk, NY: IBM Corp). Given the limited sample size, descriptive statistics were reported primarily. When direct statistical comparisons were required, Independent samples Mann-Whitney U or Chi-squared Tests were used.
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