Date Published: July 20, 2017
Publisher: Public Library of Science
Author(s): Saskia Persoon, Mai J. M. ChinAPaw, Laurien M. Buffart, Roberto D. K. Liu, Pierre Wijermans, Harry R. Koene, Monique C. Minnema, Pieternella J. Lugtenburg, Erik W. A. Marijt, Johannes Brug, Frans Nollet, Marie José Kersten, M Consuelo del Cañizo.
This single blind, multicenter randomized controlled trial aimed to evaluate the effectiveness of a supervised high intensity exercise program on physical fitness and fatigue in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation.
109 patients were randomly assigned to the 18-week exercise intervention or the usual care control group. The primary outcomes included physical fitness (VO2peak and Wpeak determined using a cardiopulmonary exercise test; grip strength and the 30s chair stand test) and fatigue (Multidimensional Fatigue Inventory) and were assessed prior to randomization and after completion of the intervention or at similar time points for the control group. Multivariable multilevel linear regression analyses were performed to assess intervention effects.
Patients in the intervention group attended 86% of the prescribed exercise sessions. Of the patients in the control group, 47% reported ≥10 physiotherapy sessions, which most likely included supervised exercise, suggesting a high rate of contamination. Median improvements in physical fitness ranged between 16 and 25% in the intervention group and between 12 and 19% in the control group. Fatigue decreased in both groups. There were no significant differences between the intervention and control group.
We found no significant beneficial effects of the supervised high intensity exercise program on physical fitness and fatigue when compared to usual care. We hypothesized that the lack of significant intervention effects may relate to suboptimal timing of intervention delivery, contamination in the control group and/or suboptimal compliance to the prescribed exercise intervention.
Netherlands Trial Register—NTR2341.
High dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) improves the outcome of patients with multiple myeloma or lymphoma . Nevertheless, this treatment may negatively impact the patient’s health-related quality of life (HRQoL) [2, 3]. Among Dutch patients, the most frequently reported long-term difficulties were problems with physical fitness and fatigue . An effective additional treatment for these problems could significantly improve the HRQoL of patients treated with auto-SCT.
The EXIST study was a multicenter, prospective, single blind RCT. The study was registered at the Netherlands Trial Register (NTR2341; 27 may 2010) and approved by the Medical Ethics Committee of the Academic Medical Center (AMC; 25 June 2010) and by the boards of the Antoni van Leeuwenhoek Hospital (Amsterdam), St. Antonius Hospital (Nieuwegein), Haga Teaching Hospital (Den Haag), University Medical Center (Utrecht), Isala (Zwolle), Erasmus MC/Daniel den Hoed (Rotterdam), VU University Medical Center (Amsterdam) and Leiden University Medical Center (Leiden). The trial protocol and the CONSORT checklist are available as supplementary information (S1 Protocol and S1 Checklist) and details of the study design have been published previously [18, 19]. The authors certify that all ongoing and related trials for this intervention have been registered.
Between March 2011 and February 2014, 469 patients were screened for eligibility of whom 150 (32%) were not eligible, 113 (24%) declined to participate, 97 (21%) did not participate for unknown reasons, and 109 patients (23%) participated (Fig 1). The median age of the participants was 55 years (range 19–67; Table 1). One patient in the control group received radiation treatment during the study, and at follow-up eight patients (16%) in the intervention and six patients (13%) in the control group received maintenance therapy. Except for the larger proportion of patients with a high education level in the control group (44 vs 28%), the baseline characteristics were well balanced.
In this single blind, multicenter RCT in patients recently treated with auto-SCT we found no significant favorable effects of a supervised high intensity exercise program on physical fitness, fatigue, body composition, HRQoL, distress or physical activity compared to usual care.