Chronic Severe Pain and Use of Prescription Pain Medications in Older Survivors of Hematologic Malignancies (HM) Several Years after Treatment with Blood or Marrow Transplantation (BMT): A Report from BMTSS
Authors: Farrukh Naveed , Hageman Lindsey , Chen Yanjun , Wu Jessica , Ness Emily , Francisco Liton F. , Parman Mariel , Landier Wendy , Arora Mukta , Armenian Saro H. , Williams Grant R , Bhatia Smita 
Published: October 2019

Abstract
Background: BMT is increasingly offered to older patients with HM. The high burden of comorbidity in older BMT survivors places them at a higher risk for chronic severe pain - an issue that has not been comprehensively evaluated. We used BMTSS to investigate the prevalence and predictors of chronic severe pain several years after BMT. We examined the impact of pain on physical performance and frailty and also examined the relation between chronic severe pain and use of prescription pain medications and opioids in this population.
Methods: The cohort included 601 HM patients who had received a BMT at age ≥60y at one of 3 transplant centers between 1974 and 2014 and had survived ≥2y after BMT; 183 unaffected siblings also participated. Self-reported domains included sociodemographics, chronic GvHD, physical performance, frailty, and medication use. Clinical information obtained from institutional databases included primary HM diagnosis, donor source, and conditioning regimen. Study participants completed a detailed questionnaire that examined pain in the following 3 domains: moderate-to-severe bodily pain, prolonged pain, and moderate-to-extreme pain interference; these 3 domains were used to create a composite variable, wherein presence of ≥1 domain was indicative of "chronic severe pain". An adjusted multivariable logistic regression model for chronic severe pain was used to compare BMT survivors to siblings. Analyses restricted to BMT survivors were stratified by donor type.
Results: Survey participation rates were 62.7% and 60%, for the BMT survivors and siblings, respectively. Median age at study participation was 69.8y (61-89) for BMT survivors and 68.9y (65-80) for siblings. Median time from BMT was 5.0y (2-17) for BMT survivors. Chronic severe pain: Overall, 39.4% of the BMT survivors reported chronic severe pain; multivariable analysis revealed a 2.5-fold greater odds of BMT survivors reporting chronic severe pain (95%CI, 1.7-3.8, p <0.0001) when compared with siblings. Domain-specific prevalence and magnitude of risk of pain are shown in Fig 1. Among allogeneic BMT recipients, survivors with lower education (<high school: OR=5.2, 95%CI: 1.5-18.3, p=0.01; ref grp: >college) and lower income (<$50k: OR=6.0, 95%CI, 1.7-20.8, p=0.005; $50k-<$100k: OR=3.8, 95%CI, 1.3-11.4, p=0.02; ref group: ≥$100k) had higher odds of reporting chronic severe pain; presence of active chronic GvHD was associated with 2.3-fold higher odds, but did not reach statistical significance (p=0.1). Among autologous BMT recipients, lower income (<$50k: OR=2.2, 95%CI, 1.1-4.4, p=0.02) was associated with higher odds of reporting chronic severe pain. Pain and physical performance/frailty: Allogeneic and autologous BMT recipients with chronic severe pain were at a 2.7-fold (95%CI, 1.2-6.0, p=0.02) and 3.0-fold (95%CI, 1.9-4.9, p<0.0001) higher odds of reporting impaired physical performance, respectively, when compared to those without pain. Allogeneic and autologous BMT recipients with chronic severe pain were at 8.2-fold (95%CI, 2.4-27.6, p=0.0007) and 7.5-fold (95%CI, 3.3-16.8, p<0.0001) higher odds, respectively of having frailty when compared to those without pain. Use of prescription pain medications and opioids: Overall, 17.8% of BMT survivors reported using prescription pain medications, and 6.5% reported using opioids; those with chronic severe pain were at a 2.5-fold higher odds of using prescription pain meds (95%CI, 1.6-3.8, p<0.0001) and at a 6.0-fold higher odds of using opioids (95%CI, 2.8-12.9, p <0.0001), when compared with those without pain.
Conclusions: Nearly 40% of older BMT survivors followed for a median of 5y after BMT, report chronic severe pain. BMT survivors are at a 2.5-fold higher odds of reporting chronic severe, life-interfering pain as compared with siblings. Chronic severe pain is associated with impaired physical performance and frailty. Finally, nearly 18% of long-term BMT survivors report use of prescription medications and 6.5% are using opioids. This study draws attention to the vulnerability of older BMT survivors and provides evidence for the need to develop effective strategies to address the underlying causes of pain.

Disclosures
No relevant conflicts of interest to declare.