Neurobiology of multiple myeloma and its therapeutical use – results of the pilot study with a control arm

Česká verzia

Authors: P. Kotouček ¹; R. Enright ²; S. Gregor Sorgerová ³; Ľ. Hunáková ⁴; V. Chlebcová ³; D. Cholujová ⁵; J. Jakubíková ⁵; B. Mravec ^6,7; E. Naništová ³; Ľ. Paneková ³; J. Sedlák ^5,8
Authors place of work: Haematology Department, Broomfield Hospital, MSE NHS FT, Chelmsford, UK ¹; Department of Educational Psychology, University Wisconsin-Madison, Madison, and International Forgiveness Institute, Madison, Wisconsin, USA ²; Ústav klinickej psychológie, Fakulta psychológie, Paneurópska vysoká škola, Bratislava, Slovenská republika ³; Imunologický ústav, Lekárska fakulta, Univerzita Komenského, Bratislava, Slovenská republika ⁴; Biomedicínske centrum, Ústav experimentálnej onkológie, Slovenská akadémia vied, v. v. i., Bratislava, Slovenská republika ⁵; Fyziologický ústav, Lekárska fakulta, Univerzita Komenského, Bratislava, Slovenská republika ⁶; Biomedicínske centrum, Ústav experimentálnej endokrinológie, Slovenská akadémia vied, v. v. i., Bratislava, Slovenská republika ⁷; Nadácia Výskum Rakoviny, Bratislava, Slovenská republika ⁸
Published in the journal: Klin Onkol 2023; 37(4): 287-299
Category: Original Articles

Summary

Background: Myeloma cells, occupying a bone marrow niche, are influenced not only by neighbouring stroma cells but also by signals from the axons of sympathetic nervous system. The nervous system is directly involved in the process of myeloma progression. Among other cancers, patients with myeloma suffer the most difficult distress generating intensive adrenergic signals, causing its further progression. There is a question arising from these facts regarding whether psychological interventions, modulating a function of the nervous system, can further improve outcomes of myeloma treatments. We focus on interactions between myeloma cells and the nervous system.

Patients and methods: Twelve patients with monoclonal gamapathy of indetermined significance (MGUS) or myeloma have participated in this study; eight in the interventional arm with the intervention of forgiveness therapy and four in the control arm. The patients were in various phases of their treatment, from active observation to immuno-chemotherapy and autologous stem cell transplant. Two major types of parameters were measured during the intervention: parameters of the activity of the disease (MGUS or myeloma) and psycho-neuro-immunological parameters of the patient, such as psychological depression, anxiety, and anger by the validated test PROMIS), as well as activity of the autonomic nervous system by heart rate variability, and immune profile by flow cytometry of peripheral blood.

Results: Patients who completed the forgiveness intervention showed improvement of depression, anxiety, and anger measured by PROMIS above population average, significant expansion of physiological plasma cells CD138+38+ (P = 0.04), B memory lymphocytes CD27+ (P = 0.02), and dendritic plasmacytoid cells CD123+ (P = 0.03). Parameters of heart rate variability such as parasympatic nervous system (PNS) index, sympatic nervous system (SNS) index, stress index, standard deviation of NN intervals (SDNN) and root mean square of the successive differences (RMSSD) had improved in a majority of patients.

Conclusion: An intervention centered on forgiveness therapy was able to improve distress, reduce adrenergic signals in the autonomic nervous system, and restore parameters of the immune profile of patients with plasma cell dyscrasia who suffered from chronic stress caused by repressed anger and unforgiveness. Integrative treatment of myeloma can improve the quality of life of patients and thus affect the efficiency of immuno-chemotherapy. New randomised trials are warranted to test the integrative treatment of myeloma that might be able to improve overall survival.

Keywords:

Multiple myeloma – Sympathetic nervous system – neurobiology of cancer – forgiveness therapy

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