MPN-FIT: a randomized controlled pilot trial of supervised exercise in myeloproliferative neoplasms

Key Points

• •A structured, home-based exercise intervention in MPN was feasible, well accepted, and showed initial benefits on disease-related markers.
• •Physical activity is a potentially safe and accessible adjunct to standard treatments in this population, warranting further study.

Visual Abstract

Abstract

Myeloproliferative neoplasms (MPN) are associated with a high symptom burden and impaired quality of life (QoL), often unaided by available treatments. Physical activity has demonstrated benefits in other cancers; however, its potential has yet to be explored in MPN. This randomized controlled trial aimed to evaluate the feasibility, acceptability, and efficacy of a supervised exercise program for patients with MPN based on longitudinal assessment of symptom burden, QoL, and clinical/inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, ferritin, lactate dehydrogenase [LDH], and serum cytokines). Patients with MPN (n = 55) were randomized 3:2 to a 12-week home-based exercise intervention (flexibility/resistance/aerobics) supervised by a kinesiologist vs waitlist control. Measures included patient-reported outcome questionnaires, peripheral blood sampling, and postintervention interviews with participants. Forty-seven patients completed the trial (FIT group, n = 26; control group, n = 21). Median age was 66 years (range, 27-86), and 60% were female. All feasibility benchmarks were met, with 88% of participants satisfied and 92% with intent to continue an exercise program on a regular basis. A significant reduction in LDH was observed in FIT patients compared with controls (−14.5 U/L vs +4.0 U/L; P = .03). Patients interviewed described positive effects of the intervention on symptoms and would unanimously recommend the program to others with MPN. In this pilot study, supervised exercise was feasible, acceptable, and showed potential benefits on inflammatory/disease markers.

Introduction

Myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are chronic blood cancers associated with a high symptom burden.1, 2, 3 With no definitive pharmacological cure and stem cell transplant being an option for only a minority of cases, patients face lifelong symptoms that lead to psychological distress and impaired quality of life (QoL).^4,5 Available pharmacological agents, including Janus kinase inhibitors, provide partial symptom relief^6,7 but may be associated with significant toxicities such as infections and cytopenias.⁸ Despite treatment, many patients continue to experience significant symptom burden^9,10 and both disease- and therapy-related events have been linked to reduced life expectancy.¹¹ Suboptimal drug efficacy and the sustained risk of toxicity underscore the need to explore complementary, better tolerated approaches to improve disease management and QoL among patients with MPN.

Physical activity is gaining interest as a nonpharmacological therapeutic modality to improve cancer outcomes and is recognized for its impact on immune function (eg, enhanced immunosurveillance, reduced systemic inflammation), known to be impaired in MPN.12, 13, 14 Exercise interventions have shown benefits in reducing disease-related symptoms and improving QoL in a number of hematological malignancies.¹⁵ Aerobic-based exercise trials in lymphoma cohorts have led to improvements in drug-related side effects, fatigue, and physical condition,16, 17, 18 whereas programs in acute myeloid leukemia have demonstrated positive trends in QoL.¹⁹

Despite this, parallel research in MPN remains limited. Observational studies have linked higher physical activity levels to lower symptom burden and improved QoL in patients with MPN.^20,21 An exploratory trial showed improvements in physical capacity after an interdisciplinary exercise program,²² and a randomized trial of online yoga demonstrated benefits on sleep, pain, anxiety, and depression.²³ Although promising, these studies were either observational or limited to activity subtype (eg, yoga practice). Notably, no previous work has explored associations between aerobic exercise and inflammatory biomarkers, some of which are known to have prognostic value in MPN.²⁴ This highlights the need for prospective trials investigating feasibility, clinical impact, and patient experience vis-à-vis a structured exercise program in MPN.

The primary objectives of this study were to (1) assess the feasibility of an individualized 12-week, home-based exercise intervention in patients with MPN; (2) evaluate effects on symptom burden, QoL, and biomarkers; and (3) explore acceptability and facilitators/barriers to exercise as a symptom management tool.

Methods

Study design, setting, and participants

This multimethods, multicentric, randomized controlled trial (RCT) recruited patients from 2 university-affiliated hospitals in Montreal, Canada. All patients provided written informed consent, and the study was approved by the institutional research ethics boards at the Maisonneuve-Rosemont Hospital and Jewish General Hospital.

Study participants were recruited between March and August 2024 from the Quebec MPN registry, a pan-provincial research-based registry actively enrolling patients since 2015.²⁵ Potentially eligible registry patients were consecutively identified by treating hematologists, and were contacted by telephone by a research coordinator (M.O.) to assess interest, screen for eligibility, and obtain consent. Inclusion criteria consisted of (1) adult patients with a diagnosis of PV, ET, or MF based on World Health Organization fifth edition²⁶ or International Consensus Classification (ICC)²⁷ criteria; (2) ability to engage in light to moderate exercise (screened with the physical activity readiness questionnaire²⁸); (3) access to an electronic device with internet for kinesiologist meetings; and (4) ability to read and understand English or French. Patients were excluded if they already engaged in >150 minutes per week of moderate-intensity exercise (or 75 minutes per week of high-intensity exercise); had absolute or relative contraindications to moderate-intensity exercise²⁹; or had a history of syncope or recurrent falls within the past 3 months. MPN subtype-specific risk scores were calculated using conventional models for PV,³⁰ International Prognostic Score for ET,³¹ and dynamic or classical International Prognostic Scoring Systems for MF.^32,33

Randomization

Participants were randomized 3:2 to the exercise intervention (FIT group) or a waitlist control group, based on previous experience and anticipating loss at follow-up in intervention group.²³ Randomization was performed (Excel script) by a member of the research team with no previous contact with participants, in block sizes of 5 to allow matching between groups in each cohort. If a participant was assigned to the FIT group, contact details were sent to the kinesiologist to arrange the first group coaching session. Participants and study personnel were not blinded to the intervention.

Intervention description

Patients randomized to the FIT group received a 12-week home-based personalized physical activity intervention developed by a certified kinesiologist. The intervention included a 30-minute routine combining flexibility, balance, resistance, and aerobic exercises, to be performed 2 to 3 times per week. Participants were also encouraged to progressively increase their moderate-intensity aerobic activity, with the goal of reaching a total of 150 to 300 minutes per week.^29,34 The exercise prescription was tailored to the patient’s baseline activity level, physical condition, and preferences. At week 1, FIT group patients attended a 1-hour small-group online coaching session (4-10 participants) led by the kinesiologist, during which they received instructions and guidance on execution of the exercise routine. The routine featured 3 aerobic exercises (military walks, skip kicks, jumping jacks), 5 resistance exercises (squats, push-ups, hip raise rotations, bicep curls, sit-ups), and 5 flexibility exercises (targeting the gluteal muscles, lower back and hamstrings, pectoralis, rhomboids, and calf muscles), with alternatives provided to accommodate different fitness levels and ensure safe implementation. Strategies were offered to help participants increase their weekly moderate-intensity exercise. Individual follow-up meetings with the kinesiologist were held at week 4 to provide support and adapt the program as needed, with additional follow-up via email at week 8 to monitor progress. Participants could also contact the kinesiologist at any time by email if changes to the exercise prescription were required.

Patients assigned to the control group were instructed to maintain their baseline physical activity level for 12 weeks, after which they were offered an optional exercise program, representative of what FIT group participants were prescribed (as a recommendation only).

Data collection

Demographic and clinical variables

Clinical data were extracted from medical records by retrospective chart review. Demographic data (self-reported) were extracted from the baseline questionnaires included in the study protocol.

Exercise adherence and safety

Participants chose between a paper-based journal or digital application (Hexfit) for activity logging. Hexfit is a digital platform designed for personalized exercise program development and delivery, enabling physical activity tracking by health professionals (eg, kinesiologists, nutritionists). All participants were instructed to record the type, duration, and intensity of all physical activity sessions performed during the study. Intensity was rated on a Borg CR-10 scale, wherein a rating of 4 to 6 corresponded to moderate-intensity exercise.³⁵ Data on baseline weekly physical activity levels were self-reported.

Feasibility

Consistent with the guidelines of Bowen et al,³⁶ acceptability was defined as ≥70% of participants reporting satisfaction with the program and ≥70% with intent to continue, assessed using a 2-item 5-point Likert scale postintervention questionnaire. A score of >2.5 was considered a positive rating. Recruitment feasibility was set at a 100% enrollment rate within 6 months.

QoL and symptom burden

Patient-reported outcomes (PROs) were assessed in all study participants at baseline (week 1), midpoint (week 6), and after intervention (week 12). We used the validated, multifactor MPN symptom assessment form (MPN-SAF), the National Institutes of Health PROs measurement information system (NIH PROMIS), and the female sexual function index (FSFI)/male sexual health questionnaire (MSHQ) scales. MPN-SAF measures included total symptom score and a single-item MPN-SAF fatigue (question number 1 on MPN-SAF). NIH PROMIS measures included the pain intensity short form 3a (3 items), emotional distress-anxiety short form 8a (8 items), emotional distress-depression short form 8a (8 items), sleep disturbance short form 8a (8 items), and global health (10 items). The FSFI measures (19 items) included total score, and 6 domain scores of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain). The MSHQ measures (18 items) included total score, and 3 scales of sexual function (ejaculation, erection, and satisfaction). These scales have been validated and are reliable for use in patients with cancer.^1,37, 38, 39, 40

Clinical/inflammatory variables

Peripheral blood samples were collected at baseline and within 1 week after intervention to assess disease-related biomarkers, including complete blood count, lactate dehydrogenase (LDH), C-reactive protein (CRP), erythrocyte sedimentation rate, and serum ferritin. Within the FIT group, cytokine level profiling was also performed for 30 cytokines and chemokines of interest (supplemental Table 1). A multiplex bead-based Luminex technology was used (Invitrogen, Carlsbad, CA). Samples were handled at 4°C and stored at −80°C until analysis. Plasma fractions were analyzed in duplicate using a Luminex analyzer (Luminex Corporation, Austin, TX), and data were analyzed using ProcartaPlex analysis software application (Thermo Fisher Connect).

Perceived experience

After intervention, individual interviews with FIT patients were conducted by members of the research team. Interviews were audio-recorded, lasting ∼30 minutes, and were conducted using a semistructured scripted format based on previous literature41, 42, 43 (supplemental Table 2), with additional prompts as needed. Topics discussed included the participant’s motivations, perceived experiences of the intervention, its impact on symptom burden and QoL, perceived barriers and facilitators to implementation, and the likelihood of maintaining physical activity after intervention.

Statistical analysis

Quantitative data

Descriptive statistics were used to summarize clinical/demographic characteristics and physical activity data, with continuous variables being summarized as median (range/interquartile range [IQR]) and categorical variables, as frequency (percentage).

Feasibility outcome measures, as previously defined, were calculated as percentages and compared with benchmark values (defined in “Feasibility”).

Changes in PRO scores (MPN-SAF, NIH PROMIS, FSFI/MSHQ) were compared for each domain at each time point between cohorts. Effect sizes were generated for all PRO domains calculated as a mean difference between FIT and control groups divided by pooled standard deviation, interpreted per Cohen d (0.2, small; 0.5, moderate; 0.8, large).

Normality assumptions for continuous variable distributions were checked using the Shapiro-Wilk test. Differences in distributions between groups were compared using the independent samples t test for normally distributed data or the Mann-Whitney U test for nonparametric distributions for continuous variables and the χ² test for categorical variables. Within the FIT group, cytokine levels at baseline and after intervention were compared using the Wilcoxon signed-rank test. Significance threshold was set at P value <.05, except within the cytokine assay, for which the Bonferroni correction was applied to account for multiple comparisons. Conventional statistics were used (JMP Pro 18.1.2; SAS Institute, Cary, NC). Data were analyzed per protocol.

Qualitative data

Semistructured interviews were transcribed verbatim. Iterative data analysis included data condensation/presentation and development and verification of findings.^44,45 Results were identified related to activity experience and activity barriers/facilitators (QDA Miner software version 5.0.28). Study quality was ensured per criteria of internal credibility and validity (crossjudge validation between members), procedural accountability (documentation of research process), and external transferability/validity (detailed description of context).^44,45

Results

Participant characteristics

A total of 107 individuals were approached for participation; 33 declined before eligibility screening, most commonly citing lack of time. The remaining 74 patients consented to screening, of whom 19 were excluded for not meeting eligibility criteria. A total of 55 patients with MPN were randomized, and 47 participants completed the trial (FIT, n = 26; control, n = 21). The Figure 1 CONSORT (Consolidated Standards of Reporting Trials) flow diagram details the participants’ flow through the study. Baseline characteristics were similar between groups (Table 1). The median age was 66 years (range, 27-86), and most participants were female (60%), White (87%), and had attained at least a college-level education (72%). The distribution of MPN subtypes was 49% ET, 32% PV, and 19% MF (P = 1.0). Most patients harbored a JAK2V617F (Janus kinase 2 V617F mutation) driver mutation (79%), followed by CALR (calreticulin; 17%; P = .5). Nearly half of the cohort (49%) was classified as having high-risk disease per International Prognostic Score for ET, dynamic or classical International Prognostic Scoring Systems for MF, or conventional model (age/leukocyte count/thrombosis for PV), and 30% had splenomegaly at baseline. Most patients were on active antiplatelet therapy (75%) and cytoreductive treatment (77%) at the time of study.

Figure 1.

CONSORT flow diagram. PAR-Q+, physical activity readiness questionnaire.

Table 1.

Participant baseline demographic and clinical characteristics

	Control (n = 21 [45%])	FIT (n = 26 [55%])	Total (N = 47)	P value
	n (%)/median (range)
Hospital center
JGH	2 (10)	4 (15)	6 (13)	.6
MRH	19 (90)	22 (85)	41 (87)
Age (y)	67 (34-86)	61 (27-78)	66 (27-86)	.5
Sex
Female	12 (57)	16 (62)	28 (60)	.8
Male	9 (43)	10 (38)	19 (40)
Ethnicity
White	18 (86)	23 (88)	41 (87)	.8
Non-White/mixed race	3 (14)	3 (12)	6 (13)
Education
Below college	7 (33)	6 (23)	13 (28)	.4
College or university	14 (67)	20 (77)	34 (72)
Employment status
Currently employed	13 (62)	13 (50)	26 (55)	.4
Not employed	8 (38)	13 (50)	21 (45)
Marital status
Married/living with a partner	16 (76)	21 (81)	37 (79)	.7
Other status	5 (24)	5 (19)	10 (21)
Comorbidities
Active smoking	2 (10)	1 (4)	3 (6)	.4
Dyslipidemia	9 (43)	9 (35)	18 (38)	.6
Hypertension	8 (38)	7 (27)	15 (32)	.4
History of depression/anxiety	3 (14)	5 (19)	8 (17)	.7
MPN subtype
ET	10 (48)	13 (50)	23 (49)	1.0
PV	7 (33)	8 (31)	15 (32)
MF	4 (19)	5 (19)	9 (19)
Driver mutation
JAK2V617F	18 (86)	19 (73)	37 (79)	.5
CALR	2 (10)	6 (23)	8 (17)
TN	1 (5)	1 (4)	2 (4)
Risk category∗
High	13 (62)	10 (38)	23 (49)	.3
Intermediate	2 (10)	4 (15)	6 (13)
Low	6 (29)	12 (46)	18 (38)
Age at diagnosis (y)	59 (28-73)	54.5 (17-68)	56 (17-73)	.8
Splenomegaly†	5 (24)	9 (36)	14 (30)	.4
Concurrent therapy
Antiplatelet therapy	14 (67)	21 (81)	25 (75)	.3
Anticoagulation therapy	3 (14)	3 (12)	6 (13)	.8
Cytoreductive agent	17 (81)	19 (73)	36 (77)	.5
Hydroxyurea	12 (57)	10 (38)	22 (47)
Ruxolitinib	2 (10)	3 (11)	5 (11)
Interferon	1 (5)	4 (15)	5 (11)
Anagrelide	1 (5)	0	1 (2)
Combination	1 (5)	2 (8)	3 (6)
History of bleeding/thrombosis
Venous thromboembolism	1 (5)	4 (15)	5 (11)	.2
Arterial thromboembolism	7 (33)	5 (19)	12 (26)	.3
Major bleeding event	3 (14)	1 (4)	4 (9)	.2

DIPSS, dynamic International Prognostic Scoring System; IPSET, International Prognostic Score for ET; IPSS, International Prognostic Scoring System; JGH, Jewish General Hospital; MRH, Maisonneuve-Rosemont Hospital; TN, triple negative.

^∗Per conventional risk models for PV,³⁰ ET (IPSET), and MF (IPSS/DIPSS).

^†Number of evaluable participants was 46.

Feasibility, adherence, and PROs

All predefined feasibility criteria were met: patient enrollment was completed within 6 months, 80% of FIT patients were satisfied with the intervention, and 92% had the intention to continue physical activity after study.

At baseline, median weekly moderate-intensity exercise duration was 0 (IQR, 0-0). Over the course of the study, FIT group participants reported significantly greater engagement in physical activity than the control group, including higher weekly moderate-intensity exercise duration (P < .001) and higher exercise intensity (P < .001; Table 2). Within the FIT group, participants completed a median of 20 FIT exercise routine sessions (IQR, 12-24), with a median session duration of 30 minutes (IQR, 23-36). Median adherence to the prescribed physical activity regimen (target frequency: 2 sessions per week) was 81% (IQR, 50%-100%; Table 3). No significant differences in adherence (P = .56) or exercise duration (P = .84) were observed between MPN subtypes (PV/ET vs MF). No adverse events or safety concerns were reported in either study group.

Table 2.

Comparison of exercise metrics logged between groups

	Control (n = 19)	FIT (n = 24)	P value
	Median (IQR)
Total exercise duration (min)	120 (0-1950)	1280 (509-2380)	.02
Weekly moderate-intensity exercise duration, RPE 4-6 (min)	0 (0-40)	58 (19-141)	<.001
Exercise intensity (RPE scale)	2 (0-4)	5 (4-5)	<.001

RPE, rate of perceived exertion (Borg CR-10 scale).

Bolded numbers are statistically significant.

Table 3.

FIT program participation metrics

	FIT (n = 24)
	Median (IQR)
Duration of FIT program (min)	30 (23-36)
Program adherence (%)	81 (50-100)
No. of FIT program sessions	20 (12-24)

Clinical/inflammatory biomarkers

Postintervention variations from baseline in biological parameters are shown in Table 4. Analyses revealed a significant reduction in LDH levels in the FIT group (−14.5 U/L vs +4.0 U/L; P = .03; Table 4). No other significant differences in markers were observed between groups over the 12-week intervention period.

Table 4.

Variations in hematological and inflammatory parameters before/after exercise intervention (FIT) vs control

	Control (n = 20)	FIT (n = 26)	P value
	Median (IQR)
Hemoglobin (g/dL)
Week 1	134.00 (121.00-141.00)	134.50 (124.00-144.00)	.90
Change at week 12	5.00 (1.25-6.75)	1.50 (−7.25 to 6.00)	.20
Hematocrit (%)
Week 1	39.85 (35.92-41.57)	39.70 (37.22-41.75)	.83
Change at week 12	1.15 (0.13-2.15)	0.25 (−1.27 to 1.70)	.13
Leukocytes (×109/L)
Week 1	5.35 (4.72-7.55)	6.90 (5.48-9.70)	.05
Change at week 12	0.45 (−0.38 to 0.70)	0.00 (−1.00 to 0.70)	.24
Neutrophils (×109/L)
Week 1	3.50 (2.80-4.98)	4.75 (3.55-6.80)	.04
Change at week 12	0.20 (−0.22 to 0.82)	0.15 (−0.58 to 0.45)	.37
Lymphocytes (×109/L)
Week 1	1.40 (1.02-1.68)	1.35 (1.00-1.70)	.84
Change at week 12	0.05 (−0.08 to 0.28)	0.00 (−0.22 to 0.20)	.33
Platelets (×109/L)
Week 1	358.50 (264.00-492.75)	396.00 (316.75-545.75)	.27
Change at week 12	3.50 (−32.00 to 34.00)	11.5 (−49.00 to 63.75)	.62
LDH∗(U/L)
Week 1	215.00 (173.00-262.75)	251.00 (186.50-543.50)	.07
Change at week 12	4.00 (−5.75 to 13.75)	−14.50 (−32.00 to −0.75)	.03
CRP†(mg/L)
Week 1	0.90 (0.18-2.90)	1.30 (0.00-1.95)	.59
Change at week 12	0.00 (−0.70 to 0.75)	0.00 (−0.30 to 0.90)	.76
ESR†(mm/h)
Week 1	8.00 (4.25-20.00)	10.00 (5.50-16.50)	.83
Change at week 12	−0.50 (−4.00 to 1.00)	0.00 (−4.00 to 3.00)	.77
Ferritin (μmol/L)
Week 1	73.60 (43.52-212.58)	67.75 (35.00-124.60)	.49
Change at week 12	1.90 (−17.78 to 9.95)	1.90 (−13.40 to 19.05)	.67

ESR, erythrocyte sedimentation rate.

^∗Number of evaluable participants was 44.

^†Number of evaluable participants was 45.

Within the FIT group, cytokine analyses demonstrated a consistent postintervention downward trend across all measured cytokines (supplemental Table 1). At the raw P value <.05 level, several cytokines showed significant reductions after intervention, including interferon gamma (IFN-γ; P = .01), eotaxin (P = .02), interleukin-1 (IL-1) receptor antagonist (P = .02), and interferon gamma-induced protein 10 (CXCL10; IP-10) (P = .006). None of these associations remained statistically significant after correcting for multiple comparisons.

PROs

Most FIT participants (54%-70%) demonstrated an improvement in PROs after intervention. A significant increase in QoL (domain of global physical health; P = .03) was observed in a subset of those presenting with baseline elevated symptom burden (MPN-SAF score of >20). Greater improvements in symptom burden (MPN-SAF) were observed in participants with longer average session duration (P = .016) and higher weekly moderate-intensity exercise duration (P = .049). Higher cumulative exercise frequency was also associated with greater reductions in fatigue (P = .043). No other meaningful effect sizes were observed between-group comparisons across PROs. A detailed summary of PRO results can be found in supplemental Table 3.

Qualitative findings

Of participants in the FIT group, 19 (73%) were invited to participate in semistructured interviews, selected to be representative of diversity in age, sex, and disease subtype.

Expectations of the program

Many patients expressed how this program was the trigger that “jumpstarted” a regular physical activity routine; this was the key motivator they had been seeking.

Perceived benefits of the FIT intervention

Benefits were perceived by patients with respect to the physical, psychological, and social aspects of their experience with MPN.

Patients described an exclusively positive impact of the program on disease-related (eg, night sweats, fatigue) and additional symptoms (eg, shortness of breath, myalgias). One of the main benefits reported was increased energy levels. A patient shared:

“There are all sorts of things that physical conditioning helps counteract, like some aspects of fatigue and the perception of having a chronic progressive illness.” (Patient 4, 48-year-old man)

Another important benefit that emerged was a sense of personal fulfillment. The same patient expressed:

“[It was like] pride and hopefulness reinjected into one’s experience of daily life despite the disease or discovering that you’re able to do something you didn’t think you were able to.”

Some also described a psychologically calming effect of regular activity. A patient conveyed:

“It gave me energy and then, I’d say it also calmed me. There was a soothing effect. Doing those exercises […] it surely acts on a psychological level. I feel that it helps me, these are good moments and after that, I’m proud to have done it.” (Patient 18, 67-year-old man; translated from French)

Additional benefits included overcoming the fear related to activity, as well as the unforeseen impact of reinforcing social connections. For example, a patient (patient 50, 52-year-old man) stated that all his friends played basketball; he had previously avoided this, due to fear of the potential ramifications on his symptoms (particularly splenomegaly). After initiating the program, he was finally able to join his friends, denoting greater confidence and understanding of what activities were achievable for him.

Barriers, facilitators, and feasibility

Perceived barriers were identified by one patient relating to the program software use (would have preferred a paper format throughout). Nearly unanimously, patients expressed how initiating the program with a family member or caregiver heightened the motivation to adhere to it. Others noted how preemptively allocating time in their schedule aided in maintaining the routine. Some highlighted how the fact that most activities could be done online/from home was an important facilitator, increasing program feasibility. It was also noted that logging the activity data was empowering, enabling them to keep track of their work and visualize their progress.

Level of satisfaction

All patients expressed that the program fulfilled their expectations, with 100% stating they planned to continue. All patients also conveyed that they would recommend the program to other individuals with MPN, if only for the benefits they perceived on their QoL.

Longer-term goals

Patients verbalized and acknowledged potential long-term benefits of the FIT program; even if their disease was currently considered “stable,” they perceived this program as an investment in their long-term health, in their future. Another critical point was the domino effect the program had on patients’ other lifestyle behaviors, with some revealing being inspired to make healthier overall choices, namely in terms of diet, in addition to increasing their physical activity.

Discussion

This pilot RCT supports the role of a structured physical activity intervention for patients with MPN. The FIT program was developed in response to the growing need for evidence-based, nonpharmacological management strategies in this population. The study met key feasibility and acceptability targets, supporting the intervention’s viability, and generated strong foundational data to support larger-scale trials.

Over the 12-week intervention, average physical activity levels were significantly higher in the FIT group than among controls, both in total duration (1280 vs 120 minutes; P = .02) and intensity (rate of perceived exertion, 5/10 vs 2/10; P < .001), reflecting patient engagement and adherence to the prescribed program. Moreover, 92% of FIT participants reported an intention to continue regular physical activity after study completion, suggesting the intervention’s potential to support sustained behavioral change beyond the study period.

Several key findings emerged. Most notably, a significant reduction in LDH levels was observed in FIT patients compared with controls, suggesting a biological response to physical activity, although levels were higher in FIT participants at baseline, which may have potentially informed results. Serum LDH is commonly regarded a marker of cellular turnover and clonal proliferation.⁴⁶ Elevated LDH levels have also been associated with a higher symptom burden in MF¹⁰ and with inferior survival in both MF and ET.^46,47 In healthy populations, LDH transiently rises after acute exercise, reflecting cell stress and micro-injury, whereas sustained training seems to improve lactate clearance during exercise without altering resting levels.48, 49, 50, 51 A plausible explanation for our findings is that exercise may attenuate inflammatory signaling and cytokine-driven myeloproliferation, leading to a relative decrease in clonal turnover and LDH release. Alternatively, the observed reductions may reflect improved mitochondrial efficiency, enhanced oxygen delivery, reduced subclinical hemolysis, or normalization of the inflammatory marrow microenvironment,⁵² all mechanisms that warrant further investigation.

In parallel, cytokine analyses within the FIT group demonstrated a consistent postintervention downward trend across all measured cytokines, although restricted with respect to statistical significance, conceivably related to limited sample size. This pattern is encouraging, given the typically elevated cytokine profiles observed in MPN.⁵³ At the unadjusted significance threshold of P value <.05, reductions were observed in IFN-γ, eotaxin, IL-1 receptor agonist, and IP-10; interestingly, cytokines putatively implicated in disease pathogenesis and associated with adverse prognosis in MPN.^53,54 The observed overall downward trend in cytokine concentrations in FIT cohorts is, thus, encouraging and consistent with previous evidence in healthy populations, demonstrating beneficial modulation of immune function with physical activity, including reductions in proinflammatory cytokines.⁵⁵

Together, these signals provide a rationale for future studies to further explore and confirm the biological effects of structured exercise in patients with MPN. Evidence examining exercise-induced changes in LDH among patients with cancer is limited, with most trials focusing on changes in CRP and proinflammatory cytokines (IL-6, IL-8, tumor necrosis factor α) after exercise.⁵⁶ Notably, in one study, physical performance was inversely correlated with pretreatment LDH levels in older adults with hematological malignancies.⁵⁷ In this study, decreases in CRP, IL-6, IL-8, and tumor necrosis factor α were observed in the FIT group; however, these did not reach statistical significance, likely reflecting the small sample size and/or confined duration of activity, rather than absence of biological effect. The isolated reduction in LDH may indicate an early metabolic adaptation to exercise; however, results should be interpreted with caution and confirmed in larger cohorts.

Regarding symptoms and QoL, although FIT group participants reported systematic improvements in PROs after intervention, questionnaires did not reveal significant differences between FIT and control groups. Several factors may explain this finding. One possibility is contamination: control group patients may have increased their physical activity in response to self-monitoring, awareness of being observed, or to align with their self-reported baseline, thereby reducing detectable difference between groups. Additionally, the relatively short duration of the intervention and the pilot study’s circumscribed sample size may have limited the ability to detect meaningful changes in symptoms or QoL. However, we observed a trend toward improved symptom burden among participants engaging in longer exercise sessions, greater weekly cumulative duration, and higher overall frequency, suggesting that exercise dose may influence outcomes. Then, in patients with a higher symptom burden at baseline, a significant improvement in the QoL domain of global physical health was observed in FIT patients compared with controls, suggesting this subgroup may derive greater benefit from the intervention. The global physical health score captures key aspects of daily functioning, including the ability to carry out everyday activities, the severity of pain and fatigue, and overall well-being. These findings are salient, because patients with the most severe symptom burden are also those most in need of supportive care, highlighting the importance of targeted interventions.

Qualitative feedback from participants highlighted significant perceived benefits, including improvements in energy, mood, and symptoms, suggesting that structured physical activity positively influences the experience of patients with MPN. Participants identified several factors contributing to engagement, satisfaction, and motivation to continue activity, with the flexibility of completing sessions at home cited as a major advantage, particularly with more than half of participants working full time. This observation is consistent with previous work by Huberty et al, who reported that the flexibility of a home-based yoga program helped patients with MPN integrate the practice into their daily routines, without the logistical burden of attending in-person sessions.⁴³ Overall, the intervention was well accepted and positively perceived by participants. These insights, a meaningful complement to quantitative findings, underscore the importance of incorporating both objective and subjective patient assessments in prospective trials.

To our knowledge, this is the first study to evaluate the feasibility and impact of a structured physical activity intervention in patients with MPN. MPN are malignancies characterized by relatively long survival, often spanning several years/decades.⁵⁸ This underscores the importance of supportive strategies, such as exercise, that can improve long-term QoL in this population, a need our study directly addresses. MPN subtype distribution and participant age in this study closely reflect real-world clinical epidemiology,⁵⁹ and our patient sample included a broad range of clinical presentations, including those with/without splenomegaly and those considered both lower and high risk. The intervention was evaluated within a robust methodological framework, using a mixed-methods design that integrated clinical outcomes with patient perspectives. This approach provided valuable insights into the mechanisms explaining adherence and satisfaction, as well as the key barriers and facilitators to implementation. Additionally, the use of a waitlist control model proved particularly effective, as evidenced by full retention in the control arm.

This study has several limitations. The small sample size and differential loss at follow-up between groups may limit the robustness and validity of findings. Although recruitment targets were met, 33 patients (31% of those approached) declined participation before eligibility screening, primarily due to time constraints; these patients may have differed from those enrolled, potentially affecting the generalizability of findings. Future recruitment strategies should emphasize the accessibility and flexibility of home-based programs, which can be integrated into diverse schedules and lifestyles. Our eligibility criteria limited participation to individuals fluent in English or French and having access to an electronic device, which may also reduce generalizability to more diverse or resource-limited populations. In addition, although activity levels were monitored, they relied on self-reported data. Future trials should consider the use of wearable devices to enhance the accuracy and objectivity of measurements. Finally, larger-scale studies with extended follow-up are needed to better understand the sustainability of exercise interventions over time, as well as their long-term effects on disease progression, symptom burden, QoL, and survival among patients with MPN. A subsequent nationwide RCT using the same digital intervention framework is planned, as well as a follow-up assessing the durability of physical activity behaviors 12 months after program completion. Potential challenges to scalability, being addressed before expansion, include variability in institutional infrastructure and workflows, patient digital literacy, and the availability of specialized personnel (eg, kinesiologists) across centers.

This study is, to our knowledge, the first RCT to evaluate feasibility and impact of physical activity in patients with MPN. Supervised exercise was feasible and acceptable, with potential salutary associations with disease-related and inflammatory signaling. Patients expressed significant physical and psychological benefits of exercise.

Conflict-of-interest disclosure: The authors declare no competing financial interests.