ENERGIA: Exercise in Rare Hematologic Diseases With Individualized and Adapted Management

Myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, as well as chronic myeloid leukemia (CML), are chronic hematologic conditions characterized by prolonged survival but a substantial and persistent symptom burden. Among these, fatigue represents one of the most prevalent and disabling symptoms, often persisting despite optimal disease control. Its pathophysiology is multifactorial and involves chronic low-grade inflammation, immune dysregulation, neuroendocrine alterations, impaired mitochondrial function, and reduced physical capacity.

Exercise has emerged as a promising non-pharmacological intervention capable of targeting several of these mechanisms simultaneously. Acute and chronic exercise are known to modulate inflammatory pathways, improve mitochondrial efficiency, enhance autonomic regulation, and increase cardiorespiratory fitness and muscle strength. These adaptations are biologically plausible mediators of improvements in fatigue and overall functional status. However, evidence specifically addressing patients with MPN and CML remains limited, and data on feasibility, safety, and mechanistic responses are still scarce.

This study is a prospective, single-arm, interventional trial designed to evaluate the feasibility, safety, and preliminary efficacy of a structured, personalized exercise program in patients with MPN and CML. The intervention consists of a 12-week supervised program combining aerobic and resistance training, delivered twice weekly, with additional home-based aerobic activity to achieve recommended weekly exercise volumes. Exercise intensity is individualized based on baseline clinical and cardiopulmonary exercise testing parameters.

Participants will undergo a comprehensive multidimensional assessment at baseline (T0), after the intervention (T1), and at follow-up (T2). Outcomes include feasibility measures (adherence and retention), safety (adverse events), and clinical endpoints such as fatigue, fatigability, cardiorespiratory fitness, physical function, body composition, cardiovascular risk profile, and psychosocial well-being. In addition, the study includes exploratory analyses of immunometabolic responses, integrating metabolomic and inflammatory biomarker profiling to investigate potential biological mechanisms underlying clinical changes.

The results of this study are expected to provide clinically relevant data on the implementation of exercise as a supportive therapy in patients with chronic hematologic malignancies and to inform the design of future controlled trials.