Упражнения и питание в гематологических заболеваниях: свидетельства перевода и новые меры вмешательства.

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Introduction

Hematologic malignancies encompass neoplasms of the hematopoietic and lymphoid tissues, with >100 subtypes categorized into 3 main groups, including leukemia, lymphoma, and multiple myeloma. In 2024, it was estimated that there would be 62 770 new cases of leukemia, 89 190 new cases of lymphoma, and 35 780 new cases of multiple myeloma in the United States alone. 1 The 5-year survival rates varied from 90% for Hodgkin lymphoma to 38% for myelodysplastic syndromes. 2 Advancements in treatment have improved survival, yet many patients continue to experience significant treatment-related toxicities and associated impaired quality of life (QoL). 3

Exercise and nutrition are established modifiable lifestyle factors that reduce cancer risk and mitigate treatment-related side effects among people with solid tumors, with the bulk of evidence in breast, prostate, and colorectal cancers. 4 The American College of Sports Medicine roundtable further supports 30 minutes of moderate-intensity aerobic exercise 3 times per week and 30 minutes of resistance exercise 2 times per week for those with cancer. 5 The American Cancer Society (ACS) and the American Institute for Cancer Research/World Cancer Research Fund guidelines on diet recommend a nutrient-rich diet for cancer survivors. 6 , 7 Despite these recommendations, hematologic malignancies remain underrepresented in oncology-related exercise and nutrition research. The heterogeneity of diseases, with varying courses, unique treatment-related toxicities, and frequent hospitalizations, poses challenges for conducting intervention studies. Consequently, evidence supporting exercise and nutrition in solid tumors may not directly translate to this understudied population.

The purpose of this narrative review is to evaluate the current evidence on exercise and nutrition across the hematologic malignancy continuum and to identify research gaps requiring investigational prioritization in exercise and nutrition research for adults with hematologic malignancies. Given the broad scope of this review, evidence from various hematologic malignancies is presented as appropriate.

Prevention

The etiology of hematologic malignancies is multifactorial, with emerging evidence suggesting that diet and physical activity may influence disease risk ( Figure 1 ). Improved testing, awareness, and access to care have led to earlier identification of precursor conditions, including monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, monoclonal B-cell lymphocytosis, and clonal hematopoiesis of indeterminate potential (CHIP). These precursor states provide an opportunity for early lifestyle interventions, although evidence in this setting remains limited.

Physical activity is inversely associated with adiposity and inflammation and is positively correlated with immune function. 8 , 9 Exercise, defined here as structured, goal-oriented movement, may influence immune surveillance by enhancing the clearance of senescent neutrophils and increasing macrophage, T-cell, and natural killer cell activity. 10 Observational studies suggest an inverse association between physical activity and hematologic malignancy risk, although findings have not been uniform. Selected studies are presented in Table 1 . In a pooled prospective cohort of 1.44 million participants, high vs low leisure-time physical activity was associated with a lower risk of acute myeloid leukemia and other myeloid neoplasms (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70-0.92), as well as multiple myeloma (HR, 0.83; 95% CI, 0.72-0.95). 11 Similarly, the VITamins And Lifestyle (VITAL) Study reported a reduced risk of hematologic malignancies among individuals in the highest recreational physical activity tertile compared with those individuals who reported no recreational activity (HR, 0.66; 95% CI, 0.51-0.86), particularly for myeloid neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other mature B-cell lymphomas, excluding plasma cell disorders. 12 , 13 In contrast, several systematic reviews and meta-analyses have reported null or inconclusive associations between physical activity and overall hematologic malignancy risk. 14 , 15

Research on diet and hematologic malignancy risk is more limited, in part because of measurement challenges in dietary assessment. However, observational studies suggest that plant-based dietary patterns, with or without fish, may be associated with reduced risk across several hematologic malignancies. 16 For example, pooled analyses from the Oxford Vegetarian Study and EPIC-Oxford cohorts demonstrated a lower risk of lymphatic and hematopoietic cancers among vegetarians and vegans than among meat eaters (relative risk [RR], 0.64; 95% CI, 0.49-0.84), with the strongest association observed for multiple myeloma (RR, 0.23; 95% CI, 0.09-0.59). 17 Similarly, higher adherence to a plant-based diet in the National Institute of Health-American Association of Retired Persons cohort was associated with reduced multiple myeloma risk (quartile 4 vs quartile 1; HR, 0.83; 95% CI, 0.71-0.96), 18 whereas higher empirical dietary inflammatory pattern scores, reflecting diets associated with increased systemic inflammation, were linked to increased risk in the Nurses’ Health Study and Health Professionals Follow-up Study risk (HR, 1.16; 95% CI, 1.02-1.32 per standard deviation increase). 19

Additional observational studies support inverse associations between the intake of fruits, vegetables, whole grains, cruciferous vegetables, and fish with risk of MGUS and multiple myeloma, whereas sugar-sweetened beverages and diets high in processed foods have been associated with increased risk. 17 , 20 , 21 , 22 In the United Kingdom Biobank cohort, unhealthy dietary patterns characterized by low fruit and vegetable intake and high consumption of processed foods were associated with a 25% increased risk of CHIP. 23 Associations with leukemia and non-Hodgkin lymphoma are less consistent but generally suggest similar protective trends with plant-based diets. 24 , 25 , 26 , 27 , 28

Summary

Together, observational data suggest that higher levels of physical activity and dietary patterns emphasizing minimally processed, plant-based foods may be associated with a lower risk of select hematologic malignancies, particularly myeloid neoplasms, multiple myeloma, MGUS, and CHIP, potentially through effects on inflammation, immune function, and metabolic health. However, findings remain heterogeneous and largely observational, and no randomized trials have evaluated diet or exercise for the primary prevention of hematologic malignancies. Early pilot studies on MGUS and smoldering multiple myeloma suggest that high-fiber, plant-based dietary interventions are feasible and may improve QoL and metabolic risk factors (to date, no interventional studies have addressed leukemia prevention). 29 Until stronger evidence becomes available, lifestyle guidance should align with established ACS, American Institute for Cancer Research/World Cancer Research Fund, and American College of Lifestyle Medicine recommendations supporting diets rich in fruits, vegetables, legumes, and whole grains, with reduced intake of processed foods and sugar-sweetened beverages, alongside regular physical activity. Future research should prioritize mechanistic and interventional studies, particularly in high-risk and precursor populations.

Treatment: HSCT

Exercise interventions during hematopoietic stem cell transplantation (HSCT) are well studied and are increasingly recognized as an important adjunct to supportive care. Several systematic reviews and meta-analyses have been published that summarize evidence in this patient population. Among these are 2 large meta-analyses, published in 2013 and 2022, which included 8 and 25 randomized controlled trials (RCTs), respectively. 30 , 31 Findings from these analyses demonstrated that exercise during HSCT is feasible, safe and improves cardiorespiratory fitness, muscle strength, and functional status, with smaller effects on upper-body strength, QoL, and cognitive outcomes. A more recent meta-analysis published in 2025 included 8 RCTs and further confirmed improvements in functional capacity, fatigue, muscle strength, and QoL among patients participating in exercise programs. 32

Exercise modality, supervision level, and timing (ie, before HSCT, after HSCT in the inpatient, or after HSCT in the outpatient setting) vary across studies. 30 , 31 Nonetheless, evidence suggests pretransplant exercise may produce the greatest functional benefits, whereas inpatient and outpatient exercise after HSCT may primarily mitigate treatment-related decline rather than reverse it. 33 , 34 Exercise before, during, and after HSCT has also been shown to reduce postdischarge mortality in a large minimally supervised exercise trial. 35

Weight loss during HSCT is associated with adverse outcomes, including higher nonrelapse mortality and prolonged hospitalization. 36 , 37 Accordingly, the European Society for Clinical Nutrition and Metabolism guidelines recommend ensuring adequate nutritional intake during transplantation, although supporting evidence remains limited. 38 One study suggests that structured inpatient nutritional monitoring may improve energy intake and reduce weight loss. 39 However, practice patterns vary widely across transplantation centers, reflecting the lack of standardized nutritional protocols. Evidence comparing oral, enteral, and parenteral nutrition is heterogeneous, but randomized trials suggest that enteral nutrition may reduce graft-versus-host disease risk compared with parenteral nutrition, without clear effects on survival or mucositis. 40 , 41 Glutamine-supplemented parenteral nutrition has been associated with reduced infection risk, shorter hospital stays, and lower early mortality in selected settings, whereas oral glutamine supplementation has not demonstrated benefit. 42 , 43 , 44 , 45 Observational studies also link inadequate nutrition and excessive reliance on parenteral nutrition with higher nonrelapse mortality, supporting the use of enteral nutrition when feasible. 46 Current guidelines therefore discourage routine parenteral nutrition but support its targeted use, including glutamine-supplemented formulations in selected patients. 47

Dietary infection-prevention strategies remain an area of active investigation. Although earlier studies did not demonstrate a benefit of a neutropenic diet, a recent randomized trial suggests that a more liberalized diet is not a safe alternative to a low-bacterial neutropenic diet in patients undergoing HSCT for acute leukemia, and that the liberalized diet did not improve dietary intake, symptoms, or QoL compared with the neutropenic diet. 48 , 49 , 50

Treatment: non-HSCT

Exercise interventions during induction chemotherapy and outpatient treatment are feasible and safe across several hematologic malignancies. 51 , 52 , 53 , 54 , 55 , 56 A 2022 meta-analysis of 15 studies (11 RCTs) demonstrated improvements in walk test performance, maximal oxygen uptake, and QoL during treatment. 51 We present selected studies in Table 2 . Studies focused on acute leukemia show that supervised exercise is feasible even during induction chemotherapy and cytopenic phases and may reduce fatigue while improving aerobic fitness and strength. 52 , 57 , 58 , 59 Home-based exercise programs are also feasible for older adults with myeloid malignancies who receive outpatient therapy. 60 In multiple myeloma, a randomized 15-week home-based exercise program reduced anemia but did not improve fatigue, sleep, or aerobic performance. 61 , 62 In lymphoma, a supervised aerobic exercise program improved physical function, fatigue, and patient-reported well-being. 63 A recent study of a multimodal supervised exercise program demonstrated a decrease in lactate dehydrogenase levels, along with patient-reported benefits, among patients with myeloproliferative neoplasms. 56 Overall, evidence supports the feasibility and benefits of exercise during treatment. However, larger disease-specific trials are needed to confirm efficacy and establish the optimal intervention timing and delivery of exercise strategies.

There is increasing evidence to suggest that structured nutritional support during induction chemotherapy may improve caloric and protein intake and reduce treatment-related weight loss ( Table 2 ). 64 , 65 , 66 For example, the use of standardized malnutrition screening tools with subsequent nutritional evaluation has been associated with improved nutritional intake in patients who were hospitalized, and preference-based meal interventions have resulted in weight gain during treatment. 64 , 65 Additional supportive care interventions incorporating dietary counseling and assistance with meal selection have similarly improved energy intake and nutrition awareness. 66 Once again, these studies have small sample sizes, and larger confirmatory trials are needed. 66

As in HSCT, the role of neutropenic diets remains controversial. The 2022 American Society of Clinical Oncology guidelines advise against routine use of restrictive neutropenic diets and support liberalized diets based on standard food safety practices during treatment, although the strength of the evidence supporting this recommendation is weak. 67 However, as mentioned previously, a recent phase 3 randomized trial demonstrated higher major infection rates with a liberalized diet than with a neutropenic diet among patients undergoing induction chemotherapy for acute leukemia, without improvement in caloric intake or QoL. 50 These findings highlight the need for disease- and treatment-specific dietary guidance for hematologic malignancies, particularly during periods of profound neutropenia

Mixed settings

Other exercise intervention studies in hematologic malignancies have focused on a heterogeneous group of survivors who may or may not have been receiving treatment or undergone HSCT. Selected studies are presented in Table 3 . For example, a 12-week home-based exercise program with telephone counseling improved aerobic physical activity and QoL compared with unsupervised exercise alone among patients with various hematologic malignancies, whereas a similar program in myelodysplastic syndrome survivors improved the 6-minute walk distance but not fatigue. 68 , 69 Among lymphoma survivors, both supervised and self-directed aerobic exercise programs improved cardiovascular fitness, fatigue, QoL, and muscle strength. 70 Mind–body interventions, such as Tibetan yoga, have also demonstrated improvements in sleep quality, although effects on fatigue and mood outcomes were limited. 71 Evidence regarding dietary interventions in hematologic malignancy survivorship is limited. One study suggests that digital lifestyle interventions using goal setting, mobile health trackers, and social media support may improve targeted dietary factors. 72

Summary

Current guidelines from the American College of Sports Medicine and the American Society of Clinical Oncology support regular aerobic and resistance exercise for most adults receiving or recovering from cancer treatment, with tailored modifications as needed. 5 , 67 Exercise interventions are associated with improvements in physical function and treatment-related symptoms and may support treatment completion and recovery across hematologic malignancies. Overall, heterogeneity in intervention timing, delivery, and outcome assessment limits the ability to draw conclusions about optimal exercise strategies, especially outside of the HSCT setting. 2 , 4 Importantly, patients with hematologic malignancies such as acute leukemias often face greater barriers to exercise participation because of intensive therapies, cytopenias, infection risk, and fluctuating functional status, necessitating closer monitoring and more conservative safety considerations than patients with more chronic indolent diseases such as chronic lymphocytic leukemia/small lymphocytic lymphoma. Nutritional assessment remains essential because of the high risk of malnutrition during treatment, although evidence supporting specific dietary interventions is more limited and heterogeneous. Additional prospective, randomized studies are needed to define optimal nutrition strategies across disease subtypes and treatment settings. As survival improves, the extended survivorship phase highlights the importance of supportive care strategies tailored to blood cancer survivors. 73 Current ACS dietary recommendations are commonly applied but are largely extrapolated from studies on solid tumors. 6 Overall, survivorship-focused lifestyle intervention trials remain limited, particularly outside the HSCT setting, highlighting the need for targeted studies to define safe and effective nutrition and exercise strategies across disease acuity, treatment settings, and survivorship phases.

Preclinical methods and evidence for mechanisms

The rise in evidence supporting the benefits of exercise for patients with cancer has led to an increase in preclinical studies investigating underlying mechanisms ( Figure 2 ). Myokines, muscle-derived factors released into the bloodstream, support cellular metabolism and are secreted during exercise. Although not fully understood, changes in myokine levels, including interleukin-6, irisin, and secreted protein acidic rich in cysteine, have been identified as potential targets for understanding the role of exercise in cancer progression. 74

The benefits of exercise have been demonstrated in numerous solid tumors, including breast, colon, prostate, lung, and melanoma. 75 Rodent models are commonly used to study exercise-tumor interactions, with tumors induced chemically, genetically, or via transplantation. Multiple voluntary and forced exercise interventions developed for use in this model require careful consideration. For example, voluntary wheel running, a natural exercise model, lacks controlled training loads, thereby complicating cancer-related research. 76 Swimming is used as an alternative to running, but strength training lacks an established rodent model. 77 Studies in rodent models have shown that exercise can reduce tumor incidence, multiplicity, and growth. 78 A systematic review of 26 studies found no overall effect of physical exercise on metastatic markers, although variability in methodology (forced vs voluntary exercise and moderate- vs intense-exercise) limited the conclusions. 79

In vivo preclinical mouse models provide important mechanistic insights into hematologic malignancies. These mouse models are also increasingly used to examine how nutrition influences cancer development via modulation of the gut microbiome and host immune responses. Dietary composition is a key determinant of microbiome diversity and function, with high-fat diets promoting protumorigenic signaling. 80 On the other hand, fiber-rich diets support beneficial microbial communities and anti-inflammatory metabolites. 81 In solid tumors, reviews have highlighted diet-induced cancer differentiation, invasion, and metastasis. 82 , 83 However, the effects of exercise- and nutrition-mediated alterations in the microbiome on hematological malignancies remain underexplored. A recent translational study using a mouse model of the multiple myeloma precursor state showed that a high-fiber diet delayed disease progression to multiple myeloma by improving gut microbiome composition and immune function, independent of calorie restriction and weight loss. 29 Clinically, among allogeneic HSCT recipients, lower gut microbial diversity early after transplantation has been associated with higher 1-year mortality. 84 Among multiple myeloma survivors receiving lenalidomide maintenance, higher stool butyrate concentrations, linked to greater intake of seafood, plant protein, and dietary flavonoids, were associated with sustained minimal residual disease negativity. 85

Conditioned serum from exercising patients provides another approach for understanding the underlying mechanisms between exercise and cancer progression. Blood collected after a single bout of exercise or after months of exercise training is analyzed for pre- vs post-exercise myokine changes. 86 , 87 Cancer cell lines incubated with conditioned serum can then be used to assess proliferation and colony formation. 74 A systematic review and meta-analysis of 9 in vitro studies found that serum collected from individuals after acute exercise reduced cancer cell viability, particularly after high-intensity exercise. 88 However, variability in exercise protocols before serum collection limits mechanistic insights. For example, Dethlefsen et al observed increased myokine and interleukin-6 levels in serum collected immediately after 2 hours of exercise but decreased myokine levels after 6 months of exercise training. 89 Another study injected postexercise peripheral blood mononuclear cells into leukemia mouse models and demonstrated that exercise mobilized effector lymphocytes with antitumor profiles. 90 Combining patient-derived exercise cells with mouse models may improve preclinical exercise research.

Most serum-based studies rely on traditional 2-dimensional (2D) cell culture, which fails to mimic tumor microenvironments. Although mouse models are physiologically relevant, they are costly and lack control over exercise. 77 Microfluidic devices represent an alternative approach, enabling precise fluid and cell manipulation ( Figure 2 ). 91 Made from inexpensive, transparent polymers such as polydimethylsiloxane, these devices mimic physical and chemical microenvironments while requiring minimal reagents. They can also model fluid shear stress, a key factor in metastasis. Regmi et al developed a microfluidic system that mimics the pulsatile shear stress of the femoral artery during intense exercise, showing that 90% of circulating breast cancer cells were killed within 4 hours, compared with 10% under resting (traditional 2D culture) shear stress. 92

Efforts to bridge 2D cell culture and mouse models include 3D culture systems that replicate bone marrow and tumor microenvironments. Techniques such as 3D spheroids, bioprinting, and microfluidic devices are used to study tumor progression and drug resistance in hematological malignancies, particularly multiple myeloma ( Figure 2 ). Carreras et al developed a microfluidic platform for coculturing patient-derived multiple myeloma cells with mesenchymal stem cells to replicate disease niches. 93 Hydrogel scaffolds, including acrylic polymers, agarose, or fibronectin and collagen layers, further enhance multiple myeloma modeling of bone marrow and tumor microenvironments in situ conditions. Despite these advancements, research has focused on drug response, with no applications evaluating exercise or nutrition in tumor progression. 94 To date, preclinical studies exploring the effects of exercise on cancer have been limited to solid tumors. This underscores the need for research investigating the mechanistic benefits of exercise and expanding research on microfluidic systems in hematologic malignancies.

Methodologic challenges & future directions

Despite growing interest in exercise and nutrition interventions across the hematologic malignancy care continuum, important methodological challenges continue to limit the interpretation and translation of existing evidence ( Table 4 ). Many studies are small, single-center trials conducted in heterogeneous patient populations across different treatment phases, with substantial variability in intervention design, timing, and outcome selection, making cross-study comparisons difficult and limiting the ability to provide disease-specific recommendations. Recruitment is further constrained by small eligible populations and timing challenges during intensive therapy, while treatment-related toxicities such as cytopenias and fatigue affect adherence to lifestyle interventions. Compared with HSCT populations, prevention and nontransplant treatment settings remain understudied. In addition, older adults, who make up the majority of patients with hematologic malignancies, are markedly underrepresented in lifestyle intervention trials. Table 4 also highlights opportunities to address these gaps through multicenter collaboration, standardized intervention frameworks, harmonized outcome measures, and geriatric-informed trial design.

Additional priorities include developing scalable delivery strategies, such as home-based and digitally supported interventions, to improve feasibility during intensive treatment and address adherence barriers. Integrating lifestyle interventions into routine oncology workflows and designing disease- and treatment-specific nutritional guidance (eg, during neutropenia and HSCT) will help standardize delivery across various settings. Expanding research in prevention and early disease states, including high-risk precursor conditions such as CHIP, MGUS, and smoldering myeloma, represents an important opportunity to extend lifestyle strategies earlier across the cancer continuum. Selected ongoing trials addressing these priorities are summarized in Table 5 .

Future research should also prioritize mechanistic and longitudinal studies to clarify how exercise and nutrition influence disease biology, treatment tolerance, and survivorship outcomes across hematologic malignancies ( Figure 3 ). In particular, studies integrating immune, metabolic, microbiome, and bone health pathways, including the role of lifestyle factors in skeletal complications, may help identify biologically informed intervention targets. Adequately powered multicenter randomized trials with harmonized outcome measures are needed to evaluate the effects of exercise and nutrition interventions on cancer- and treatment-related symptoms and functional recovery. Embedding lifestyle interventions within standard oncology care will further support pragmatic trial designs and improve the translation of lifestyle strategies into routine clinical practice.

Conclusion

Exercise and nutrition intervention research in hematologic malignancies is limited compared with solid tumors, particularly in prevention and posttreatment survivorship settings. Nevertheless, existing studies consistently demonstrate feasibility and safety, with emerging evidence supporting benefits for physical function, symptom burden, and QoL. Future rigorously designed trials across the cancer continuum are needed to define optimal intervention timing, delivery strategies, and underlying biological mechanisms, and to determine whether lifestyle interventions can influence treatment tolerance, disease progression, and survival in this growing population of blood cancer survivors. 95

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

Acknowledgments

Authorship

Contribution: All authors conceived of the idea and wrote the manuscript.

Footnotes

K.P.L. and M.J.-B. contributed equally to this study.

Data are available from the corresponding author, Kah Poh Loh ( kahpoh_loh@urmc.rochester.edu ), on request.

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