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Allogeneic stem cell transplant is the only treatment that has the potential to cure myelofibrosis.

"It's very important to include stem cell transplant in 2024 -- and beyond -- in every conversation," said Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center in Houston.

However, transplant is only pursued by a small percentage of patients with myelofibrosis, with experts suggesting that only 5% to 10% actually undergo the procedure.

"It's certainly a very small minority -- and it's less than should go to transplant," said Ruben Mesa, MD, of Atrium Health Wake Forest Baptist Comprehensive Cancer Center in Charlotte, North Carolina.

While patients have access to medical therapies that have been beneficial, "transplant as a salvage therapy for myelofibrosis has been limited in terms of options," Mesa said. "The time that patients do best with transplant is probably before they feel they need them. That is, in part, because therapies have been very effective in helping them feel better and in clearly providing some genuine relief, but sometimes it can inadvertently lead to a delay in transplant, when it would have been helpful if they had gone earlier."

Indications for and Against Transplant

According to , patients with asymptomatic, lower-risk myelofibrosis should be observed and monitored for signs and symptoms of disease progression.

While outcomes following transplant are usually improved for lower-risk patients, there is a risk of morbidity and mortality. Thus, the guidelines suggest that treatment decisions should be individualized and that transplant should be considered in patients with refractory, transfusion-dependent anemia, circulating blast cells greater than 2% in peripheral blood, adverse cytogenetics, or molecular abnormalities.

Evaluation for allogeneic stem cell transplant is recommended for all patients with higher-risk myelofibrosis, and the procedure is recommended for patients who meet transplant eligibility criteria based on age, performance status, major comorbid conditions, psychosocial status, patient preference, and availability of caregivers.

The guidelines further suggest that bridging therapy can be used to decrease marrow blasts prior to transplant, and that prior exposure to the JAK inhibitor ruxolitinib (Jakafi) may improve outcomes after transplant. They also recommend the continuation of JAK inhibitors close to the start of conditioning therapy in order to improve splenomegaly and other disease-related symptoms.

While transplant offers the potential for success, outcomes vary. However, there are prognostic markers that could potentially predict transplant outcomes in myelofibrosis.

For example, the is a model that takes into account ages ≥57 years, Karnofsky performance status <90%, platelet count <150 × 10⁹/L and leukocyte count >25 × 10⁹/L at time of transplantation, HLA-mismatched unrelated donor, and ASXL1-mutated and CALR-/MPL-unmutated genotype as independent prognostic factors for outcome.

It stratifies patients into four risk categories -- low, intermediate, high, and very high -- and when validated in a cohort of 156 patients it showed 5-year survival rates for these risk groups of 83%, 64%, 37%, and 22%, respectively.

Moreover, according to data from the , survival with stem cell transplant for myelofibrosis has been steadily increasing over the years, with 3-year survival rates of 46%, 49%, and 54% for the time periods 2001-2005, 2006-2010, and 2011-2017.

However, Mesa suggested that for patients, "the difficult part of the decision [to undergo transplant] is that the morbidity and mortality of transplant is very front-loaded. If cured, your potential for significant gains in length of life is substantial. What you risk, however, is a much more front-loaded risk of mortality and morbidity -- you could live 15 years, or could pass away in 4 months."

A for 551 transplant patients and 1,377 non-transplant patients suggested that there was a long-term survival advantage with transplant for patients with Dynamic International Prognostic Scoring System intermediate-1 or higher-risk myelofibrosis, but with increased early mortality, "thus highlighting the need for careful patient selection and continued development of therapies aimed at reducing post-hematopoietic cell transplantation complications."

While the advantage of undergoing transplant is the possibility for a long-term cure, there are several factors that make patients hesitant or ineligible.

Mesa noted that the vast majority of patients with myelofibrosis are ages 60 years and older, with life-threatening comorbidities involving the lungs, heart, and kidneys.

"And, of course, there are real-world factors such as having a donor, having a center that is accessible, being able to get high-intensity chemotherapy with the stem cell transplant as rescue, infection risks, and graft-versus-host disease," Mesa added.

Age itself won't prevent a patient from going to transplant. that examined trends in the use of stem cell transplantation for myelofibrosis in Europe reported that the median recipient age increased from 49 years before 2006 to 59 years in 2018, with an increase in patients over the age of 70.

However, "as you get older into the 70s, the bar continues to climb higher and higher for making the case that it's a good decision for our patients," Mesa noted, adding that poor performance status, insufficient available family support, and concerns about the ability to comply with the rigor of undergoing a transplant are all factors that could go into a decision to rule out the procedure.

Patient Preference

Patient preference is "the central part" of whether myelofibrosis patients eventually undergo transplant, and joint decision making between the patient, the patient's caregiver and family, and the referring and transplant physicians should occur, said Pemmaraju.

"Transplant is a serious decision -- it comes with serious morbidity and mortality risk that increases as you get older with more comorbidities," he said. "Patients may decide not to go for it due to logistical reasons, personal reasons, and health reasons. Sometimes you don't get the insurance coverage or clearance, sometimes there are external events like the donor falls through for various reasons."

"So, there are a lot of patient-centered reasons for why patients may choose not to go for transplant when eligible and available," he continued. "This is getting better over time, but it is a sobering reminder that the majority of these patients end up not being able to go for it."

Pemmaraju estimated that about 20% to 25% of his patients actually end up undergoing transplant. "Can we improve this marker over time?" he asked. "I would say yes. Can we develop immunotherapy and other therapies that can cure the disease without transplant? I hope so. Can we come up with brand-new platforms and approaches that can eradicate the disease before transplant? Again, possibly. So these are things we are working on in the lab and in early clinical trials, and this is exactly what we need to be doing."

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