RESUMO
With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate inter-study comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to i) account for gender-specific differences in determining hemoglobin levels for eligibility criteria, ii) revise definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices, and iii) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks prior to study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs. non-TDA) and graded (major vs. minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.
RESUMO
Advances in anticancer therapies have provided crucial benefits for millions of patients who are living long and fulfilling lives. While these successes should be celebrated, there is certainly room to continue improving cancer care. Increased long-term survival presents additional challenges for determining whether new therapies further extend patients' lives through clinical trials, commonly known as the gold standard endpoint of overall survival (OS). As a result, there is an increasing reliance on earlier efficacy endpoints , which may or may not correlate with OS, to continue the timely pace of translating innovation into novel therapies available for patients. Even when not powered as an efficacy endpoint, OS remains a critical indication of safety for regulatory decisions and is a key aspect of the U.S. Food and Drug Administration's Project Endpoint. Unfortunately, in the pursuit of earlier endpoints, many registrational clinical trials lack adequate planning, collection, and analysis of OS data, which complicates interpretation of a net clinical benefit or harm. This article shares best practices, proposes novel statistical methodologies, and provides detailed recommendations to improve the rigor of using OS data to inform benefit-risk assessments, including incorporating the following in clinical trials intending to demonstrate the safety and effectiveness of a cancer therapy: prospective collection of OS data, establishment of fit-for-purpose definitions of OS detriment, and prespecification of analysis plans for using OS data to evaluate for potential harm. These improvements hold promise to help regulators, patients and providers better understand the benefits and risks of novel therapies.
RESUMO
BACKGROUND: Early cancer recognition is key to improving patient outcomes. Diagnosis is often delayed in myeloproliferative neoplasm (MPN) patients, putting them at risk of thromboembolic events and other complications pre-diagnosis. A clear understanding of the barriers to presentation and diagnosis is required. AIMS: To explore barriers and factors influencing delayed presentation and diagnosis of MPNs. DESIGN & SETTING: A cross-sectional study of MPN patients within the United Kingdom and the Republic of Ireland. METHOD: An online cross-sectional survey of MPN patients. Symptoms and factors influencing patient and General Practitioner (GP) delay were examined. Adjusted odds ratios (aOR) were calculated to explore the relationship between these factors and patient/GP delay. RESULTS: Most (80.2%) of the 620 patients completing the survey reported symptomatic presentation. The most common symptoms associated with patient delay were pruritus (aOR 1.89, 95% CI 1.19-3.01), headaches (aOR 1.86, 95% CI 1.13-2.82) and concentration difficulties (aOR 1.75, 95% CI 1.12-2.76). Attributing symptoms to ageing (aOR 1.92, 95% CI 1.19-3.11) and not wanting to burden the GP (aOR 2.17, 95% CI 1.35-3.50) were significantly associated with patient delay. Those reporting >3 blood cancer warning signs were more likely to experience GP delay than those experiencing fewer (aOR 3.26, 95% CI 1.75-6.29), and lack of relational continuity of GP care was significantly associated with GP delay (aOR 3.41, 95% CI 1.65-7.28). CONCLUSION: Debunking misconceptions around ageing, encouraging timely communication with GPs and improving relational continuity of GP care could assist in reducing diagnostic delays, prevent potentially fatal disease complications and ultimately improve MPN patient outcomes.
RESUMO
There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of JAK2-mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials. Novel agents, such as hepcidin mimetics, aim to help patients with PV restore normal hematocrit levels and become phlebotomy-free. In this review, we will summarize past, current and future approaches to PV management and highlight findings from key clinical studies.
RESUMO
The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 109/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (n = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (n = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.
RESUMO
Patients with myeloproliferative neoplasms (MPNs) face chronic symptom burden. Online symptom assessment studies allow for recruitment of large numbers of motivated patients, but patient self-selection can lead to sampling bias. This study evaluated how gender representativeness in MPN symptom surveys and trials impacted symptom score mean estimates, using data from 4825 survey respondents and 291 trial participants with MPNs. The survey data showed that men participated at a rate roughly 50% less than what would be expected based on prevalence, and women reported higher scores than men on average for six of 10 symptoms. Together, this led to potential over estimation in six of 10 symptom score means (ranging from 5.8% to 15.3% overestimated). The trial data showed less gender-based sampling bias compared to the survey data. Studies utilizing online symptom surveys should implement study design features to recruit more men, assess for gender participation imbalances, and provide weighted estimates where appropriate.
RESUMO
Myeloproliferative neoplasms (MPN) are characterized by a clonal proliferation of myeloid lineage cells within the bone marrow. The classical BCR-ABL negative MPNs are comprised of polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Historically, the majority of MPNs are diagnosed in adults older than 60 years of age; however, in recent years, there has been recognition of MPNs in the adolescent and young adult (AYA) population. AYAs with MPN, typically defined as between the ages of 15 and 39 years old, may comprise up to 20% of patients diagnosed with MPN. They demonstrate unique patterns of driver mutations and thrombotic events and remain at risk for progression to more aggressive disease states. Given the likely long length of time they will live with their disease, there is a significant unmet need in identifying well-tolerated and effective treatment options for these patients, particularly with the advent of disease modification. In this review, we provide a comprehensive overview of the clinical features, disease course and management of AYA patients with MPN and, in doing so, highlight key characteristics that distinguish them from their older counterparts.
Assuntos
Transtornos Mieloproliferativos , Humanos , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/terapia , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/genética , Adolescente , Adulto , Adulto Jovem , Masculino , FemininoRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0278354.].
RESUMO
The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); patients in cohort 3A/3B had stable ruxolitinib treatment prior to and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary endpoint was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary endpoint. In cohorts 1 and 3A (NTD), 27% and 50% of patients respectively had mean hemoglobin increase ≥1.5 g/dL from baseline. Among TD patients, ~50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. NCT03194542 clinicaltrials.gov.
RESUMO
Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production resulting in elevated hemoglobin and/or hematocrit levels. Patients often have symptoms such as fatigue, pruritus, and painful splenomegaly, but are also at risk of thrombosis, both venous and arterial. Ruxolitinib, a selective Janus kinase inhibitor, is approved by the US Food and Drug Administration as second-line cytoreductive treatment after intolerance or inadequate response to hydroxyurea. Although ruxolitinib has been widely used in this setting, limited data exist in the literature on ruxolitinib treatment patterns and outcomes among patients with PV in routine clinical practice. We report a retrospective, observational, cohort study of patients treated for PV with ruxolitinib across three US centers (academic and regional practice) from December 2014-December 2019. The study included 69 patients, with a median follow-up duration of 3.7 years (95% CI, 2.9-4.4). Our data demonstrate very high rates of hematocrit control (88% of patients by three months and 89% by six months); few patients required dose adjustments or suspension. No arterial thromboses were observed; however, the follow-up duration does not allow for the generation of meaningful conclusions from this. Three patients had thrombotic events; one was in the setting of a second malignancy, one post-operative, and a third related to prolonged immobility. We also found that 28% of patients initiated ruxolitinib as a result of poorly controlled platelet counts, second only to hydroxyurea intolerance (46%) as a reason to start therapy. In clinical practice, ruxolitinib continues to be effective in controlling hematocrit levels after three and six months of treatment in patients and is associated with low thrombotic risk.
Assuntos
Nitrilas , Policitemia Vera , Pirazóis , Pirimidinas , Trombose , Humanos , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Policitemia Vera/tratamento farmacológico , Policitemia Vera/complicações , Policitemia Vera/sangue , Pirimidinas/uso terapêutico , Feminino , Masculino , Hematócrito , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Trombose/etiologia , Trombose/prevenção & controle , Idoso de 80 Anos ou mais , Adulto , SeguimentosRESUMO
A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838; N = 432, JAK inhibitor naive, momelotinib vs. ruxolitinib); subgroups were defined by baseline hemoglobin: <10 (moderate/severe), ≥10 to <12 (mild), or ≥12 g/dL (nonanemic). Spleen and symptom results were generally consistent with those previously reported for the intent-to-treat population. In anemic subgroups, momelotinib was associated with higher rates of transfusion independence and reduced/stable transfusion intensity vs. ruxolitinib. No new or unexpected safety signals were identified. Overall, momelotinib provides spleen, symptom, and anemia benefits to JAK inhibitor-naive patients with myelofibrosis regardless of baseline hemoglobin level, and greater anemia-related benefits vs. ruxolitinib in patients with hemoglobin <12 g/dL.
Assuntos
Hemoglobinas , Nitrilas , Mielofibrose Primária , Pirazóis , Pirimidinas , Humanos , Pirimidinas/uso terapêutico , Pirazóis/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Hemoglobinas/análise , Hemoglobinas/metabolismo , Idoso , Resultado do Tratamento , Benzamidas/uso terapêutico , Método Duplo-Cego , Anemia/etiologia , Anemia/diagnóstico , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Idoso de 80 Anos ou mais , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/genética , Janus Quinase 2/antagonistas & inibidoresRESUMO
Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.
A review of what interferons are and how they are used in the treatment of the myeloproliferative neoplasms polycythemia vera, essential thrombocythemia, and primary myelofibrosis Why was this paper written? This paper was written to summarize the current clinical landscape of the use of interferons for the treatment of myeloproliferative neoplasms (MPN). What are interferons and how are they used in MPNs? Interferons are small proteins involved in cellular signaling that have been used to treat MPNs, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), for more than 35 years. They can have modulatory effects on the immune system and on the fundamental causes of disease. The use of interferons as treatment was initially limited due to difficulties with their administration and the potential for significant adverse effects. Many of these shortcomings were addressed by chemically binding a biocompatible polymer, polyethylene glycol (PEG), to the structure of the interferon, which increases the stability of the protein, prolongs the time during which it is active, and reduces negative effects to the immune system. The combined chemical structure of PEG and interferon (pegylated interferon or peginterferon) is recommended for use in the treatment of PV, ET, and PMF. What topics are discussed in this paper? In this review paper we evaluate the clinical effectiveness and safety of two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi) and discuss the practical clinical management of interferon-based therapies, along with the authors' opinions on whether to and how to switch therapy from hydroxyurea. Key topics and questions related to the use of interferons, such as their safety and tolerability, the significance of their effects on mutated cells, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. What do the findings mean? Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.
RESUMO
PURPOSE: Chronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN. EXPERIMENTAL DESIGN: We randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. RESULTS: The Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. CONCLUSIONS: With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions. SIGNIFICANCE: Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.
Assuntos
Dieta Mediterrânea , Transtornos Mieloproliferativos , Neoplasias , Humanos , Estados Unidos , Projetos Piloto , Estudos de Viabilidade , Transtornos Mieloproliferativos/terapia , Inflamação , NutrientesRESUMO
OBJECTIVES: Patients with myelofibrosis develop symptoms due to bone marrow fibrosis, systemic inflammation, and/or organomegaly. Alleviating symptoms improves overall quality of life. Clinical trials have historically defined symptom response as a reduction of at least 50% in Total Symptom Score at week 24 compared with baseline. Whether 50% constitutes a meaningful benefit has not been established. This study determined the meaningful change threshold (MCT) for 2 momelotinib phase III trials, SIMPLIFY-1 and SIMPLIFY-2. METHODS: The absolute and percentage MCT was determined using anchor-based methods applied to the modified Myeloproliferative Neoplasm Symptom Assessment Form v2.0 and Patient Global Impression of Change. MCTs were applied retrospectively to determine responder rates. Generalized estimating equations estimated the treatment-related difference in likelihood of improvement. RESULTS: In SIMPLIFY-1, a Janus kinase inhibitor-naive population, the MCT was 8 points. In SIMPLIFY-2, a previously Janus kinase inhibitor-treated population, the MCT was 6 points. A 32% MCT was determined in both studies, showing that the historic 50% reduction threshold may be a conservative choice. In SIMPLIFY-1, a similar proportion of patients achieved responder status with 24 weeks of momelotinib or ruxolitinib therapy based on the absolute MCT (39% vs 41%, respectively). In SIMPLIFY-2, a significantly greater proportion of patients treated with momelotinib achieved responder states compared with best available therapy based on absolute and percent change MCTs. CONCLUSIONS: This study demonstrates that momelotinib provided clinically meaningful symptom benefit for patients with myelofibrosis and provides insight into the appropriateness of the symptom change threshold used in historical studies.
Assuntos
Mielofibrose Primária , Pirimidinas , Qualidade de Vida , Humanos , Mielofibrose Primária/tratamento farmacológico , Pirimidinas/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Pirazóis/uso terapêutico , Benzamidas/uso terapêutico , Nitrilas/uso terapêuticoRESUMO
Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor-naive patients from SIMPLIFY-1 (NCT01969838), a double-blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of ≥1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with ≥1-grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.
Assuntos
Nitrilas , Mielofibrose Primária , Pirazóis , Pirimidinas , Humanos , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Método Duplo-Cego , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease and poor prognosis. ASXL1 recruits Polycomb repressive complex 2 (PRC2) to specific gene loci to repress transcription through trimethylation of histone H3 on lysine 27 (H3K27me3). ASXL1 alterations reduce H3K27me3 levels, which results in leukemogenic gene expression and the development of myeloid malignancies. Standard therapies for myeloid malignancies have limited efficacy when mutated ASXL1 is present. We discovered upregulation of lysine demethylase 6B (KDM6B), a demethylase for H3K27me3, in ASXL1-mutant leukemic cells, which further reduces H3K27me3 levels and facilitates myeloid transformation. Here, we demonstrated that heterozygous deletion of Kdm6b restored H3K27me3 levels and normalized dysregulated gene expression in Asxl1Y588XTg hematopoietic stem/progenitor cells (HSPCs). Furthermore, heterozygous deletion of Kdm6b decreased the HSPC pool, restored their self-renewal capacity, prevented biased myeloid differentiation, and abrogated progression to myeloid malignancies in Asxl1Y588XTg mice. Importantly, administration of GSK-J4, a KDM6B inhibitor, not only restored H3K27me3 levels but also reduced the disease burden in NSG mice xenografted with human ASXL1-mutant leukemic cells in vivo. This preclinical finding provides compelling evidence that targeting KDM6B may be a therapeutic strategy for myeloid malignancies with ASXL1 mutations.
Assuntos
Histonas , Neoplasias , Humanos , Camundongos , Animais , Histonas/metabolismo , Lisina , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismoRESUMO
New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis. To inform patients' optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic International Prognostic Scoring System score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. Reduced intensity conditioning and myeloablative conditioning are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making.