Country-Specific Guidelines on Anemia Management for Patients with Myelofibrosis in Latin America, the Middle East, and East Asia: A Systematic Literature Review

Introduction: Anemia is a common manifestation of myelofibrosis (MF); it has been identified as a predictor for overall survival and has been shown to increase morbidity, reduce quality of life, and increase healthcare resource utilization. Guidelines on myeloproliferative neoplasms from the National Comprehensive Cancer Network in the US are regarded as the global standard for treating patients; however, whether other country-specific guidelines exist is unclear. The aim of this literature review was to explore the existence of country-specific guidelines in Latin America, the Middle East, and East Asia, and compare their recommendations for anemia management in MF.

Methods: A systematic literature review using the PRISMA-P guidelines was conducted to obtain guidelines, consensus recommendations, or expert opinions on the treatment and management of MF in 17 countries or groups of countries (Argentina, Bahrain, Brazil, Caricom, Chile, Colombia, Ecuador, India, Kuwait, Mexico, Oman, Peru, Qatar, Russia, Saudi Arabia, Turkey, and United Arab Emirates). The search strategy included country names and terms related to MF, such as myeloproliferative neoplasm. Medical databases (PubMed, Embase, LILACS, BVS, and SciELO), and publications and reports from health ministries, national health organizations, and relevant medical associations in each country were reviewed up to 1 February 2024.

A blind review was performed independently by two authors (RBG and JL). In case of disagreement, a third assessor was consulted. After exclusion of duplicate records, the selection process was conducted by screening titles and abstracts, then reading the full text of the documents. Guidelines published in English, Portuguese, Spanish, Turkish, and Russian were included. References cited in eligible guidelines were reviewed manually to identify further eligible documents. One author performed the initial data extraction for all documents, and a second author reviewed all results for accuracy. Data extraction was focused on cut-offs to establish anemia, management of the disease, and indication of transfusion.

Results: The search only identified 3 guidelines from the following countries: India (2018), Brazil (2019), and Russia (2020).

The guidelines revealed a lack of unified standard of care for the management of anemia in patients with MF, and a lack of standardized direction for starting anemia treatment and transfusion requirements. The Brazilian guidelines recommended interferon and recombinant human erythropoietin (EPO); however, the guidelines noted that the response rate for EPO was variable, and EPO appeared to be more effective in transfusion independent patients and those with less severe anemia. Immunomodulatory therapy was recommended when no other effective treatment options were available. The Indian guidelines recommended EPO as first-line therapy with danazol as an alternative in cases associated with transfusion-dependent anemia, and thalidomide plus prednisolone for patients not responding to EPO or danazol. The Russian guidelines recommended iron supplementation, erythropoiesis-stimulating agents, or corticosteroids, depending on the underlying cause of anemia.

Only the Russian guidelines addressed the issue of administering red blood cell transfusions, indicated in cases of anemia. The guidelines stated that urgency and volume of transfusion should be determined by the degree of circulatory failure, not hemoglobin level. Also, target hemoglobin concentration during transfusions should be above 70 g/l and above 90 g/l if cardiovascular pathology is available. The guidelines also defined transfusion dependency as the need for frequent blood transfusions (more than two units of red blood cells within 30 days) to maintain hemoglobin levels within a specified target range without an alternate means of correction.

Conclusions: These results highlight the lack of guidelines for the general treatment and management of MF in Latin America, the Middle East, and East Asia, the limited information on anemia and transfusion dependency, and the limited treatment options currently available. The findings also identify the need for an updated and unified standard of care for the treatment of anemia in patients with MF, especially in light of novel therapies that could help improve clinical outcomes and prevent transfusion dependency.

Teichman:GlaxoSmithKline: Current Employment. Grigolon:Oracle: Current Employment; GSK: Honoraria. Abreu:GlaxoSmithKline: Current Employment. Kim:GlaxoSmithKline: Current Employment, Current holder of stock options in a privately-held company. Soares:GlaxoSmithKline: Current Employment, Current holder of stock options in a privately-held company.