GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis.

PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, cancer treatment may have to be interrupted or delayed. In this study, we looked beyond OM's known risk factors of renal function and melphalan dose with a genome-wide association study (GWAS) to evaluate whether genetic variants in conjunction with clinical risk factors influence predisposition for OM. METHODS: Genotyping was performed using Illumina HumanOmni1-Quad v1.0 BeadChip and further assessed for data quality. We tested 892,589 germline single-nucleotide polymorphisms (SNPs) for association with OM among 972 Caucasian patients treated with high-dose melphalan and ASCT in Total Therapy clinical trials (TT2, TT3, TT4) for newly diagnosed MM. Statistical analyses included t tests, stepwise regression modeling, and logistic regression modeling to find baseline clinical factors and genotypes associated with OM. RESULTS: We found that 353 (36.3 %) patients had grades 2-4 OM. Type of treatment protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were associated with grades 2-4 OM. The addition of these SNPs increased sensitivity in detecting grades 2-4 OM cases to 52 %. CONCLUSIONS: These SNPs may be important for their roles in inflammatory pathways, epithelial healing, and chemotherapy detoxification.

Sleep measured by polysomnography in patients receiving high-dose chemotherapy for multiple myeloma prior to stem cell transplantation.

PURPOSE/OBJECTIVES: To describe the objective sleep of patients receiving chemotherapy for multiple myeloma (MM) prior to stem cell transplantation. DESIGN: A descriptive study with repeated measures. SETTING: An international referral center in an urban area of the southern United States. SAMPLE: A convenience sample of a subset of 12 patients with MM, recruited from a randomized, controlled trial. METHODS: Objective sleep was assessed using two nights of polysomnography, one obtained before and one after a second cycle of high-dose chemotherapy prior to stem cell transplantation. Demographic and clinical data were obtained through a retrospective chart review. MAIN RESEARCH VARIABLES: Objective sleep including sleep characteristics, sleep-related respiratory events, and periodic limb movements (PLMs) of sleep. FINDINGS: Sleep was characterized by a relatively short sleep time, excessive time spent awake after the onset of sleep, and poor sleep efficiency (objective sleep quality). Patients spent more than the expected percent of time in non-rapid eye movement sleep and less in rapid eye movement sleep. Arterial oxyhemoglobin saturation nadirs reflected episodes of low arterial oxygen saturation. PLMs during sleep were in the mildly elevated range. CONCLUSIONS: Findings suggest that patients had poor sleep efficiency (objective sleep quality) and were slightly better sleepers after receiving a second cycle of high-dose chemotherapy. A number of patients also demonstrated obstructive sleep apnea and frequent PLMs. IMPLICATIONS FOR NURSING: Findings support the need for additional investigation of sleep in patients with MM, particularly poor sleep efficiency and PLMs. Improving sleep may improve quality of life by decreasing associated symptoms such as pain, fatigue, and depression. KNOWLEDGE TRANSLATION: Oncology nurses should consider assessing patients with MM for insomnia symptoms, excessive daytime sleepiness, obstructive sleep apnea, and a history of jerking or kicking their legs when asleep. Those symptoms may suggest the need for additional investigation of a possible sleep disorder, which may negatively influence mood and function.