Practical Guide for Managing Philadelphia-Negative Myeloproliferative Neoplasms in Patients with Organ Dysfunction

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Classical Philadelphia-negative myeloproliferative neoplasms (MPNs) often coexist with renal, hepatic, cardiovascular, or hematologic comorbidities.
• These comorbidities complicate treatment selection, dose adjustments, and toxicity monitoring in MPN patients.
• Patients with advanced organ dysfunction are frequently underrepresented in clinical trials, limiting evidence for optimal management.

Purpose of the Study:

• To present a practical, organ-adapted framework for selecting MPN therapies in clinically complex patients.
• To compare commonly used cytoreductive and targeted therapies in the context of organ impairment.
• To guide treatment selection, dose modification, and monitoring for MPN patients with comorbidities.

Main Methods:

• Narrative review of literature on MPN management in organ dysfunction.
• Definition and comparison of renal and hepatic impairment criteria.
• Analysis of commonly used MPN therapies including hydroxyurea, busulfan, anagrelide, and various JAK inhibitors (ruxolitinib, fedratinib, momelotinib, pacritinib).
• Discussion of therapy application in specific scenarios like dialysis, decompensated liver disease, and cytopenic or anemia-dominant myelofibrosis.

Main Results:

• A framework is proposed prioritizing label-based dose modification, cautious initiation for extrapolated evidence, structured monitoring, and multidisciplinary review.
• Hydroxyurea and ruxolitinib may be feasible in renal impairment with dose adjustment and monitoring; severe impairment requires conservative approaches.
• JAK inhibitor selection in myelofibrosis should be phenotype-adapted (e.g., momelotinib for anemia, pacritinib for thrombocytopenia).
• Therapy in hepatic dysfunction or combined organ vulnerability should prioritize safety, reversible factors, conservative starts, and early reassessment.

Conclusions:

• MPN management in organ dysfunction must be individualized based on disease phenotype, treatment goals, organ reserve, and safety restrictions.
• Dose adjustment, close monitoring, and multidisciplinary input are crucial for managing MPNs in patients with comorbidities.
• Phenotype-adapted JAK inhibitor selection and a safety-first approach are essential in myelofibrosis and hepatic dysfunction, respectively.