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Chronic opioid use can be reduced or discontinued after haematopoietic stem cell transplantation for sickle cell disease

Pain is a complex experience for individuals with sickle cell disease (SCD). Acute vaso-occlusive crises (VOCs) cause nociceptive pain. Chronic neuropathic, post-stroke or avascular necrosis (AVN)-related pain may complicate the pain experience. Chronic opioid use may be fraught with opioidinduced hyperalgesia, tolerance, opioid use disorder, constipation, endocrine changes and sedation. Allogeneic haematopoietic stem cell transplantation (HSCT) is an effective treatment for SCD that can lead to long-term correction of haemolysis and anaemia. It offers a unique model to evaluate the aetiologies of pain in SCD, as the sickling of deoxygenated erythrocytes is eliminated. Thus, HSCT provides the opportunity to better understand opioid use patterns and to find optimal tapering strategies. We retrospectively investigated opioid tapering patterns in adults with SCD (aged ≥18 years) undergoing successful HSCT at the University of Illinois Hospital and Health Sciences System between 2012 and 2018. Opioid prescribing records 1 year before and several years after HSCT were obtained from a Cerner-embedded pharmacy prescription reporting system. Patient data were collected from the electronic medical records. Oral opioid medication doses were converted to oral morphine equivalents (OME). A total of 37 patients with SCD underwent HSCT and achieved stable long-term engraftment, defined as ≥20% donor myeloid chimerism at 2-years after HSCT. In all, 15 patients received routine care at other institutions before or after HSCT without obtainable opioid information. Of the 22 patients with opioid records available, five (23%) were not taking opioids before HSCT and this proportion increased to 77% by the last year of follow-up (median length 37 months; P = 0 0007). Among the 17 patients who required opioids before HSCT, the median (interquartile range [IQR]) age was 31 (25–37) years at transplantation, and 71% were males. Seven patients underwent HSCT using a haploidentical related donor and 10 from a human leucocyte antigen (HLA)-matched related donor. Only one patient in the haploidentical group and none in the fully matched group developed chronic graft-versus-host disease. The median (IQR) opioid dose at 1 year before HSCT was 9 (2– 52) mg OME/day, which decreased to 5 (0 7–54), 0 3 (0–55), and 0 (0–7) mg OME/day during the first, second and last year of follow-up after HSCT (P = 0 028, Fig 1). In all, 12 patients (71%) were successfully tapered off opioids, defined as no opioid use for 12 consecutive months. The five patients not weaned off opioids had significantly higher opioid use in the year before HSCT than the 12 that were off opioids (59 vs. 2 1 mg OME/day, P = 0 02). History of AVN, socioeconomic status as measured by area deprivation index (ADI) score, and pre-HSCT haemoglobin and white blood cell count were comparable between the two groups (Table I). The Centers for Disease Control and Prevention (CDC) recommends extra caution for opioid doses of ≥50 mg OME/ day. In all, 11 of the 12 patients who used <50 mg OME/ day before HSCT were tapered off opioids, whereas one of five patients using ≥50 mg OME/day was tapered off opioids (P = 0 010). Four patients who used >25 mg OME/day before HSCT were subsequently tapered off opioids. Subject #1 had a history of bilateral hip AVN and was taking 147 mg OME/day before HSCT. His opioid usage gradually declined to 72 mg OME/day over 5 years. This was followed by a rapid naltrexone-facilitated detox procedure in an acute facility and a dose of long-acting injectable naltrexone upon discharge from the programme. Subsequently, he received three doses of long-acting intramuscular naltrexone injections from the addiction psychiatry service, and no longer required opioids. Subject #2 was taking 34 mg OME/day before HSCT for acute VOC and AVN in the right elbow and left knee. His pain improved post-HSCT after two orthopaedic surgeries followed by physical therapy. He slowly tapered off his Fig 1. Opioid dose pattern before and after haematopoietic stem cell transplantation. The y-axis is a square-root scale. The data were compared using a repeated-measures analysis of variance. correspondence