Anaemia in myelofibrosis is a multifaceted problem with a major affect on affected person outcomes, writes Theresa Lowry Lehnen
Myelofibrosis is a uncommon, continual 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 variety of issues, together with splenomegaly, extramedullary haematopoiesis, and a variety of systemic signs resembling fever, evening sweats, and weight reduction. Some of the difficult elements of managing myelofibrosis is its affiliation with reasonable to extreme anaemia, a complication that considerably impacts sufferers’ high quality of life and total prognosis.1, 2
The pathophysiology of myelofibrosis includes mutations in genes resembling JAK2, CALR, and MPL, which drive irregular mobile proliferation. These mutations stimulate an overproduction of inflammatory cytokines, creating an atmosphere that disrupts regular haematopoiesis. In consequence, 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 usually progressive and could also be worsened by further components, resembling splenic sequestration, elevated pink blood cell turnover, or treatment-related cytotoxicity.1, 2
Anaemia in myelofibrosis is often characterised by a low haemoglobin stage typically beneath 10 g/dL and is usually refractory to traditional therapies. The diploma of anaemia is a vital 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 accessible therapies are restricted, and response charges range. Transfusions are steadily required, particularly in instances of reasonable to extreme anaemia, however they supply solely short-term aid and may result in issues resembling iron overload.1, 2, 3
A number of therapeutic methods goal to handle anaemia in myelofibrosis, though every has limitations. Erythropoiesis-stimulating brokers (ESAs) are sometimes utilized in an try and 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 applicable for sufferers with important splenomegaly, as they could exacerbate splenic enlargements and associated signs.1, 2, 3, 4
One other therapy possibility is the usage of androgens resembling danazol, which has proven modest efficacy in some sufferers with myelofibrosis-related anaemia. Danazol could stimulate erythropoiesis and enhance haemoglobin ranges, however its use is usually restricted by potential unwanted side effects, together with hepatotoxicity and masculinising results in ladies. The response to danazol is variable, and long-term advantages are nonetheless underneath investigation.1, 2, 3, 4
Immunomodulatory medication, resembling 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 steadily related to important unwanted side effects, together with neuropathy and myelosuppression. Mixture remedy with corticosteroids could improve their effectiveness, though this method can result in further antagonistic results, notably with extended use.1, 2, 3, 4
The emergence of JAK inhibitors (JAKi), resembling ruxolitinib and fedratinib, has reworked the therapy panorama for myelofibrosis, particularly for symptomatic splenomegaly and constitutional signs. Nevertheless, their results on anaemia are complicated. Whereas JAK inhibitors can enhance anaemia in some sufferers by lowering splenic sequestration and cytokine burden, they’ll additionally exacerbate anaemia, particularly through the preliminary phases of therapy. 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 energetic substance momelotinibis is a drugs used to deal with splenomegaly or different disease-related signs in adults with myelofibrosis who even have reasonable 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 kinds 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 situations are uncommon, Omjjara has been designated as an ‘orphan medication,’ a standing given to therapies for uncommon ailments.6, 7, 8
New therapeutic approaches have been underneath investigation to particularly goal anaemia in myelofibrosis. Luspatercept, an erythroid maturation agent, has proven promise in scientific 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 recommend that luspatercept could scale back transfusion necessities in a subset of sufferers, though additional analysis is required to ascertain its efficacy and security profile on this inhabitants.1, 2
Stem cell transplantation stays the one healing possibility 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 bear transplantation, anaemia could initially worsen because of myeloablative conditioning, however profitable engraftment can result in normalisation of blood counts, together with haemoglobin. Nevertheless, transplantation shouldn’t be a viable possibility for a lot of sufferers because of age, comorbidities, and different danger components.1, 2, 3, 4
Administration of anaemia in myelofibrosis requires a tailor-made method, contemplating every affected person’s illness traits, signs, and therapy objectives.
Supportive care with pink blood cell transfusions stays a cornerstone of administration for sufferers with reasonable to extreme anaemia, however the dangers related to continual transfusions, resembling iron overload and alloimmunisation, complicate long-term administration.
Iron chelation remedy could also be required in transfusion-dependent sufferers to forestall issues 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 medication, 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 therapy 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. 
Creator
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. Out there right here.
- Passamonti, F., Harrison, C., Mesa, R., Kiladjian, J., Vannucchi, A., Verstovsek, S. (2022). Anaemia in myelofibrosis: Present and rising therapy choices, Vital Critiques in Oncology/Haematology. Quantity 180, 2022. Out there 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 recent applied sciences in myeloproliferative neoplasms. Entrance. Oncol. 2019, 9, 321.
- Bose, P., Verstovsek, S. (2020). JAK inhibition for the therapy of myelofibrosis: Limitations and future views. Hemasphere 2020, 4, e424.
- European Medicines Company. Omjjara. Out there 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. Out there 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 therapy for myelofibrosis sufferers with anaemia. J Hematol Oncol 15, 7 (2022). Out there 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
