Anaemia in myelofibrosis is a multifaceted problem with a major affect on affected person outcomes, writes Theresa Lowry Lehnen
Myelofibrosis is a uncommon, power myeloproliferative neoplasm characterised by the irregular proliferation of hematopoietic stem cells, leading to bone marrow fibrosis and impaired blood cell manufacturing.
This situation results in a spread of problems, together with splenomegaly, extramedullary haematopoiesis, and a spread of systemic signs akin to fever, night time sweats, and weight reduction. One of the vital difficult points of managing myelofibrosis is its affiliation with average to extreme anaemia, a complication that considerably impacts sufferers’ high quality of life and total prognosis.1, 2
The pathophysiology of myelofibrosis entails mutations in genes akin to JAK2, CALR, and MPL, which drive irregular mobile proliferation. These mutations stimulate an overproduction of inflammatory cytokines, creating an atmosphere that disrupts regular haematopoiesis. Consequently, fibrosis develops within the bone marrow, resulting in decreased area and capability for blood cell manufacturing, finally inflicting cytopenia’s, together with anaemia.
Anaemia in myelofibrosis is commonly progressive and could also be worsened by further components, akin to splenic sequestration, elevated pink blood cell turnover, or treatment-related cytotoxicity.1, 2
Anaemia in myelofibrosis is usually characterised by a low haemoglobin stage typically beneath 10 g/dL and is commonly refractory to standard therapies. The diploma of anaemia is a crucial determinant within the prognosis of sufferers with myelofibrosis, as decrease haemoglobin ranges correlate with poorer survival outcomes. Administration of anaemia in these sufferers is difficult, as out there therapies are restricted, and response charges differ. Transfusions are ceaselessly required, particularly in instances of average to extreme anaemia, however they supply solely non permanent aid and may result in problems akin to iron overload.1, 2, 3
A number of therapeutic methods intention to deal with anaemia in myelofibrosis, though every has limitations. Erythropoiesis-stimulating brokers (ESAs) are sometimes utilized in an try to stimulate pink blood cell manufacturing, however are typically efficient solely in sufferers with decrease ranges of endogenous erythropoietin and restricted to these with much less extreme anaemia. ESAs is probably not acceptable for sufferers with vital splenomegaly, as they could exacerbate splenic enlargements and associated signs.1, 2, 3, 4
One other remedy choice is using androgens akin to danazol, which has proven modest efficacy in some sufferers with myelofibrosis-related anaemia. Danazol might stimulate erythropoiesis and enhance haemoglobin ranges, however its use is commonly restricted by potential unintended effects, together with hepatotoxicity and masculinising results in ladies. The response to danazol is variable, and long-term advantages are nonetheless below investigation.1, 2, 3, 4
Immunomodulatory medicine, akin to thalidomide and lenalidomide, have additionally been explored for his or her potential to enhance anaemia in myelofibrosis. These brokers can stimulate erythropoiesis and scale back splenomegaly, however they’re ceaselessly related to vital unintended effects, together with neuropathy and myelosuppression. Mixture remedy with corticosteroids might improve their effectiveness, though this method can result in further antagonistic results, significantly with extended use.1, 2, 3, 4
The emergence of JAK inhibitors (JAKi), akin to ruxolitinib and fedratinib, has remodeled the remedy panorama for myelofibrosis, particularly for symptomatic splenomegaly and constitutional signs. Nonetheless, their results on anaemia are advanced. Whereas JAK inhibitors can enhance anaemia in some sufferers by decreasing splenic sequestration and cytokine burden, they will additionally exacerbate anaemia, particularly through the preliminary phases of remedy. Dose changes and supportive care are sometimes essential to handle this aspect impact, however the long-term affect on anaemia stays variable.2, 3, 5
Omjjara, an antineoplastic agent containing the lively substance momelotinibis is a medicine used to deal with splenomegaly or different disease-related signs in adults with myelofibrosis who even have average to extreme anaemia. It’s prescribed for sufferers who’re both new to Janus kinase inhibitors or have beforehand been handled with the JAKi ruxolitinib.
Omjjara is efficient for 3 varieties of myelofibrosis: main myelofibrosis, the place the trigger is unknown; post-polycythaemia vera myelofibrosis, associated to an extra of pink blood cells; and post-essential thrombocythaemia myelofibrosis, linked to an overproduction of platelets. Since these circumstances are uncommon, Omjjara has been designated as an ‘orphan drugs,’ a standing given to therapies for uncommon illnesses.6, 7, 8
New therapeutic approaches have been below investigation to particularly goal anaemia in myelofibrosis. Luspatercept, an erythroid maturation agent, has proven promise in medical trials for myelofibrosis-associated anaemia by selling pink blood cell maturation and bettering haemoglobin ranges. Its mechanism differs from conventional erythropoiesis-stimulating brokers, because it immediately addresses ineffective erythropoiesis somewhat than merely stimulating erythropoietin signalling. Early research counsel that luspatercept might scale back transfusion necessities in a subset of sufferers, though additional analysis is required to determine its efficacy and security profile on this inhabitants.1, 2
Stem cell transplantation stays the one healing choice for myelofibrosis, however it’s related to excessive morbidity and mortality and is usually reserved for youthful sufferers with high-risk illness. For sufferers who endure transplantation, anaemia might initially worsen on account of myeloablative conditioning, however profitable engraftment can result in normalisation of blood counts, together with haemoglobin. Nonetheless, transplantation is just not a viable choice for a lot of sufferers on account of age, comorbidities, and different threat components.1, 2, 3, 4
Administration of anaemia in myelofibrosis requires a tailor-made method, contemplating every affected person’s illness traits, signs, and remedy objectives.
Supportive care with pink blood cell transfusions stays a cornerstone of administration for sufferers with average to extreme anaemia, however the dangers related to power transfusions, akin to iron overload and alloimmunisation, complicate long-term administration.
Iron chelation remedy could also be required in transfusion-dependent sufferers to stop problems associated to iron overload.1, 2
Anaemia in myelofibrosis is a multifaceted problem with a major affect on affected person outcomes. Whereas a number of therapeutic choices can be found, together with ESAs, androgens, immunomodulatory medicine, and JAK inhibitors, none are uniformly efficient, and every has limitations. Rising therapies provide hope for improved anaemia administration, however additional research are wanted to verify their efficacy and outline their position inside present remedy paradigms.9 A multidisciplinary method, involving haematologists, transplant specialists, and supportive care groups, is important to optimise the administration of anaemia in myelofibrosis and enhance sufferers’ high quality of life. 
Writer
Theresa Lowry-Lehnen, RGN, PG. Dip Coronary Care, RNP, BSc, MSc, PG. Dip. Ed (QTS), M. Ed, PhD, Scientific Nurse Specialist and Affiliate Lecturer South East Technological College.
References:
- Mayo Clinic (2024) Myelofibrosis. Accessible right here.
- Passamonti, F., Harrison, C., Mesa, R., Kiladjian, J., Vannucchi, A., Verstovsek, S. (2022). Anaemia in myelofibrosis: Present and rising remedy choices, Essential Opinions in Oncology/Haematology. Quantity 180, 2022. Accessible at: https://www.sciencedirect.com/science/article/pii/S1040842822002864
- Naymagon, L., Mascarenhas, J. (2017). Myelofibrosis-Associated Anaemia: Present and Rising Therapeutic Methods. Hemasphere. 2017 Dec 20;1(1): e1. doi: 10.1097/HS9.0000000000000001. PMID: 31723730; PMCID: PMC6745971.
- Palumbo, G., Stella, S., Pennisi, M., Pirosa, C., Fermo, E., Fabris, S., Cattaneo, D., Iurlo, A. The position of latest applied sciences in myeloproliferative neoplasms. Entrance. Oncol. 2019, 9, 321.
- Bose, P., Verstovsek, S. (2020). JAK inhibition for the remedy of myelofibrosis: Limitations and future views. Hemasphere 2020, 4, e424.
- European Medicines Company. Omjjara. Accessible at: https://www.ema.europa.eu/en/medicines/human/EPAR/omjjara
- Medicines and Healthcare merchandise Regulatory Company (MHRA). (2024). Omjjara licensed for anaemic myelofibrosis sufferers to deal with the signs of their illness. Accessible at: https://www.gov.uk/authorities/information/omjjara-licensed-for-anaemic-myelofibrosis-patients-to-treat-the-symptoms-of-their-disease
- Chifotides, H., Bose, P., Verstovsek, S. Momelotinib: an rising remedy for myelofibrosis sufferers with anaemia. J Hematol Oncol 15, 7 (2022). Accessible at: https://doi.org/10.1186/s13045-021-01157-4
- Duminuco, A., Nardo. A., Giuffrida, G., Leotta, S., Markovic, U., Giallongo, C., Tibullo, D., Romano, A., Di Raimondo, F., Palumbo, G. Myelofibrosis and Survival Prognostic Fashions: A Journey between Previous and Future. Journal of Scientific Medication. 2023; 12(6):2188. https://doi.org/10.3390/jcm12062188
