Primary myelofibrosis is a rare disease characterized by the proliferation of myeloid cells. The resulting pathology is progressive bone marrow failure, accompanied by extramedullary hematopoiesis and hepatosplenomegaly. 

Because of the heterogeneity in patient presentation, clinicians rely heavily on laboratory investigations to determine if clinical suspicion for this condition has reached a particular threshold. Common laboratory hallmarks include anemia, as well as white cell and platelet count that fall outside the range of normal. 

Read more about myelofibrosis etiology 

If primary myelofibrosis is suspected, clinicians usually proceed to collect a bone marrow biopsy and perform both cytogenetic and molecular analysis. The World Health Organization in 2016 adopted a series of criteria for diagnosing primary myelofibrosis that can only be assessed using the aforementioned approaches. 

“The complications of [primary myelofibrosis] include constitutional symptoms that may impact quality of life, bone marrow failure, symptomatic hepatomegaly or splenomegaly, and leukemic transformation,” Wolfe and colleagues wrote in the Journal of Personalized Medicine. 

Once a diagnosis of primary myelofibrosis has been established, physicians typically use prognostic scoring tools to predict potential clinical outcomes; these tools tend to divide risk into 3 broad categories: low, intermediate, and high risk. 

The therapies that can be used to treat primary myelofibrosis are incredibly diverse. Patients with asymptomatic disease can be adequately managed with observation and supportive care. However, in a more severe disease presentation, clinicians may consider prescribing JAK2 inhibitors, per interferón alfa-2a, or hydroxyurea; all 3 medications have been shown to reduce symptoms and splenomegaly. Another drug, ruxolitinib, may extend survival among patients with primary myelofibrosis. 

The Role of Allogeneic Hematopoietic Stem Cell Transplantation 

There is general consensus that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for primary myelofibrosis. This treatment typically has a pediatric focus, with allo-HSCT most often prescribed to young, high-risk patients. This is because a risk assessment must ensure that the potential benefits of transplantation outweigh any potential risks, which is not always the case. 

“Allo-HSCT is associated with significant treatment-related morbidity and mortality due to toxicity from conditioning regimens, graft failure, and potential development of graft versus host disease,” Wolfe et al wrote. 

Scientists have found age to be the most significant factor impacting outcomes post-transplantation; because young patients tend to have fewer comorbidities and age-related metabolic disorders, they are generally better candidates for this procedure. This is not to say that adult patients are automatically excluded from consideration; rather, they need to pass stringent presurgical analysis to ensure that this risky procedure yields tangible benefits for their long-term well-being. To better weigh the benefits and risks of this procedure, clinicians typically use the validated Hematopoietic Cell Transplantation-specific comorbidity index. 

A Closer Look at a Single-Center Study of Allogeneic Hematopoietic Stem Cell Transplantation Outcomes 

In Blood Cell Therapy, Choudhary and colleagues conducted a retrospective, single-center study to assess the merits of allo-HSCT in 15 consecutive patients with myelofibrosis. The primary endpoints of the study were overall survival and disease-free survival, while secondary endpoints were posttransplant complications. 

All 15 patients recruited for this study underwent careful donor selection to lower the risk of mismatched transplantation, a major risk factor for transplant-related mortality. Nevertheless, 27% of patients developed acute graft versus host disease, and 27% developed chronic graft versus host disease. Six patients died before engraftment; 5 were due to sepsis. 

“The [graft versus host disease] rates in our study were comparable to those reported in other studies, and mortality due to [graft versus host disease] was low,” Choudhary et al wrote. 

The research team concluded that myelofibrosis remains a challenging condition to treat and carries a poor prognosis. As evidenced by the 6 deaths prior to allo-HSCT, many patients with myelofibrosis experience morbidity before this life-changing procedure can be carried out. 

However, Choudhary and colleagues proposed that reduced toxicity conditioning was associated with a promising overall survival and disease-free survival; this should therefore be offered to patients who have a high Dynamic International Prognostic Scoring System score. 

Recommendations for Allogeneic Hematopoietic Stem Cell Transplantation 

“The use of established prognostic tools should be used to risk stratify patients who may derive the greatest benefit from allo-HSCT,” Wolfe et al stressed. “Transplantation should always be considered for individuals with intermediate-2 and high-risk disease.” 

In patients who may benefit from allo-HSCT according to objective risk-assessment parameters, clinicians should not hesitate to proceed. Granted, these parameters should be extensive, encompassing an individual’s age, comorbidities, functional status, disease-specific factors, and the availability of related donors. 

While younger patients tend to have a less complicated medical history, older patients may benefit from reduced-intensity conditioning with fludarabine and busulfan or fludarabine melphalan. Conditioning regimes and supportive care can help expand the eligibility of allo-HSCT to older individuals, even those who have some comorbidities. 

Read more about myelofibrosis treatment 

Ultimately, any medical procedure should be aimed at improving long-term clinical outcomes and extending life expectancy. Should patients be considered ineligible for allo-HSCT, physicians should make use of other therapies that can likewise reduce disease burden and improve quality of life. 

Because allo-HSCT is so rarely performed, there is still much that we do not know about this procedure. For example, questions remain regarding the benefit of early and late transplantation in lower-risk patients with myelofibrosis. In addition, researchers are unsure about how the concurrent use of JAK inhibitors around the time of transplantation can affect outcomes. However, as long as research into this area continues, our understanding of this procedure will continue to expand, potentially opening up solutions to make it more inclusive. 


Choudhary D, Doval D, Khandelwal V, Setia R, Handoo A. Allogeneic stem cell transplant for myelofibrosis — a retrospective single-center studyBlood Cell Ther. Published online February 10, 2023. doi:10.31547/bct-2022-003

Wolfe HR, Horwitz ME, Rein LAM. The use of allogeneic hematopoietic stem cell transplantation in primary myelofibrosisJ Pers Med. Published online April 2, 2022. doi:10.3390/jpm12040571