The Effect of Pre-Transplant Psychological Well-Being on Hematological Reconstitution Following Autologous Stem Cell Transplantation in Multiple Myeloma Patients
Authors: Bilgin Bilge , Gunduz Mehmet , Duman Berker , Sahin Ugur , Kumbasar Hakan , Topcuoglu Pervin , Gurman Gunhan , Beksac Meral 
Published: October 2019

Abstract
Introduction and aim: High dose chemotherapy (HDC) combined with autologous stem-cell transplantation (ASCT) is an important treatment modality in multiple myeloma (MM) and may cause a serious emotional burden on patients. Pre-transplant anxiety and depression have been shown to exert an unfavourable effect on immunologic reconstitution. This study aims to investigate whether there is any relation between pre-transplant psychological well-being and engraftment kinetics following ASCT for MM.
Methods: Thirty-eight adult MM patients scheduled for ASCT between July 2014 and June 2015 were included in this study. The study was approved by the local ethical committee. Sociodemographic data form and Hospital Anxiety and Depression Scale (HADS) were completed by the patients following written informed consent during the week before ASCT. The engraftment days were determined by routine daily complete blood count monitorization. All statistical analyses were performed by using SPSS v17.0 software package. The relation between anxiety and depression scores and the times to neutrophil and platelet engraftment was analysed by using the Mann Whitney U-test. Pearson correlation analysis was performed for investigating the relationship between continuous variables. p<0.05 was accepted as statistically significant in all analyses.
Results: Twenty four patients (63%) were male and the mean age was 56.7±7.4 years. Twenty seven patients (71.1%) underwent ASCT after the first line chemotherapy and the rest received more than one line of chemotherapy before the ASCT. According to the cut-off points of HADS, 34% of the patients had depression and 8% had anxiety. The median time to platelet engraftment was 11.5 (10-16) days and the median time to neutrophil engraftment was 12 (8-23) days. The neutrophil engraftment was significantly delayed among patients with depression (p=0.02) [Table 1]. The time to platelet engraftment tended to be longer among patients with anxiety. However, the relationship was not statistically significant (p=0.05). Neutrophil engraftment of depressive patients who underwent ASCT after the first line chemotherapy took significantly longer time, whereas the delay did not reach significance among depressive patients who had received more than one line of chemotherapy prior to ASCT (p=0.04, p=0.4, respectively). The anxiety scores and the time to platelet and neutrophil engraftment correlated positively (r=0.46, p=0.004 and r=0.65, p<0.001, respectively). A significant relation was not found between the amount of infused CD34+ cells and the number G-CSF doses, and the time to engraftment.
Table 1. Depression P Anxiety P - + - + Median (min, max) time to neutrophil engraftment (days) 11 (10-14) 12 (11-16) 0.02 11 (10-16) 12 (11-13) 0.67 Median (min, max) time to platelet engraftment (days) 12 (8-23) 12 (8-23) 0.97 11.5 (8-23) 18 (12-23) 0.05 Median (min, max) CD34 content infused (106/kg) 4.5 (3.26-8.15) 4.68 (2.90-7.89) 0.98 4.62 (3.26-8.15) 4.14 (2.90-5.91) 0.61
Conclusion: Emotional stress is known to exert negative effects on immune system. These are thought to be related with the increased production of cortisol, catecholamines and other neuropeptides. There is data on depression to cause increased levels of pro-inflammatory cytokines. According to a newly published meta-analyses, serum IL-6 and C-reactive protein levels are higher in depressive patients when compared to non-depressive patients. Our findings preoccupied that the engraftment periods were delayed in depressive patients. This effect of depression seemed to be more important among patients who underwent ASCT after one line of chemotherapy. The structural changes in the bone marrow and the treatment toxicities might exert a more deleterious effect than depression among patients who had received more than one line of chemotherapy before the ASCT. It is difficult to explain the delay in platelet engraftment among patients with anxiety. Depression causes changes in serotonine (5-HT) metabolism and its receptors, and it is known that changes in 5-HT metabolism have effects on platelet functions. In our study 3/5 of the depressed patients were using antidepressants. However, in this small series the possible positive effect of antidepressant use could not be analyzed. To our knowledge this is the first study analyzing the role of physchological well being on hematological recovery among myeloma patients.

Disclosures
Beksac: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.