Allogeneic stem cell transplantation is the only treatment that has the potential to cure myelofibrosis.
“It's really important that we include stem cell transplants in every conversation in 2024 and beyond,” said Naveen Penmaraj, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
However, only a small percentage of people with myelofibrosis seek a transplant, and experts suggest that only 5 to 10 percent actually receive a transplant.
“It's certainly a very small number, less than the number that should be going to transplants,” said Dr. Ruben Mesa of Atrium Health Wake Forest Baptist Comprehensive Cancer Center in Charlotte, North Carolina.
Although patients have access to beneficial medical treatments, “transplantation as a salvage therapy for myelofibrosis has limited options,” Mesa said. “Patients will be best served by a transplant before they feel they need it. One reason is that the treatment is so effective at making patients feel better that it clearly provides genuine relief. However, sometimes this can lead to an unintended delay in the transplant, in which case the patient would have had the transplant sooner.”
Indications and opposition to transplantation
according to National Comprehensive Cancer Center Network GuidelinesPatients with asymptomatic, low-risk myelofibrosis should be observed and monitored for signs and symptoms of disease progression.
Although outcomes after transplantation are usually improved in low-risk patients, there is a risk of morbidity and mortality. Therefore, guidelines suggest that treatment decisions should be individualized and transplantation should be considered for patients with refractory transfusion-dependent anemia, >2% circulating blasts in peripheral blood, adverse cytogenetics, or molecular abnormalities.
Evaluation for allogeneic stem cell transplantation is recommended for all patients with high-risk myelofibrosis, and the procedure is based on transplant eligibility criteria based on age, performance status, major comorbidities, psychosocial status, patient preference, and presence of caregivers. Recommended for patients who meet the criteria. .
The guidelines further suggest that bridging therapy can be used to reduce bone marrow blasts before transplantation, and that prior exposure to the JAK inhibitor ruxolitinib (Jakafi) may improve outcomes after transplantation. doing. They also recommend continuing JAK inhibitors near the start of conditioning therapy to improve splenomegaly and other disease-related symptoms.
Transplants have a chance of success, but results vary. However, there are prognostic markers that may predict transplant outcome in myelofibrosis.
for example, Clinical molecular transplant scoring system The model takes into account age 57 years or older, Karnofsky performance status <90%, and platelet count <150 × 10.9/L and white blood cell count >25 × 109/L at the time of transplantation, HLA-mismatched unrelated donor, and ASXL1– with mutation Cal-/MPL– Non-mutated genotype as an independent prognostic factor of outcome.
The study divided patients into four risk categories: low, intermediate, high, and very high risk, and in a cohort of 156 patients, the 5-year survival rates for these risk groups were 83%, 64%, and 64%, respectively. It was shown that 37% and 22%.
Furthermore, according to data from Registration of International Blood and Marrow Transplant Research CenterSurvival rates following stem cell transplantation for myelofibrosis have steadily increased over the years, with 3-year survival rates of 46%, 49%, and 54% in 2001-2005, 2006-2010, and 2011-2017, respectively.
But for patients, Dr. Mesa said, “the hardest part of the decision is [to undergo transplant] The morbidity and mortality of transplantation is very much ahead of schedule. If cured, there is a good chance your lifespan will be significantly extended. But the risks are far ahead of mortality and morbidity. They can live for 15 years or die in 4 months. ”
a Retrospective study of survival outcomes A study of 551 transplant and 1,377 nontransplant patients suggested that patients with high-risk myelofibrosis (Dynamic International Prognostic Scoring System intermediate 1 or higher) have a long-term survival benefit from transplantation but are at increased risk of early mortality, “thus highlighting the need for careful patient selection and continued development of therapies aimed at reducing complications after hematopoietic cell transplantation.”
While the benefit of undergoing a transplant is the possibility of a long-term cure, there are several factors that can make patients hesitant or unable to undergo a transplant.
Professor Mesa pointed out that the majority of patients with myelofibrosis are over 60 years old and have life-threatening complications involving the lungs, heart and kidneys.
“And, of course, there are real-world factors such as availability of donors, availability of accessible centers, availability of intensive chemotherapy with stem cell transplants as relief, risk of infection, and graft-versus-host disease.” added Mesa.
Age itself does not prevent a patient from receiving a transplant. Retrospective analysis Researchers examining trends in the use of stem cell transplants for myelofibrosis in Europe found that the median age of recipients has risen from 49 years before 2006 to 59 years in 2018, with an increasing number of patients over 70 years old. reported that it did.
But “as we age toward our 70s, the hurdles to claiming this is a good decision for the patient become higher and higher,” Mesa noted, noting decreased performance, lack of available family support, and He added that he had the following concerns: Your ability to withstand the rigors of undergoing a transplant can all influence your decision to rule out transplant surgery.
patient preference
Pemaraju said a “central part” of whether a myelofibrosis patient ultimately receives a transplant is the patient's wishes, and the decision is made jointly between the patient, the patient's caregiver or family, and the referring and transplant physician. said that it should be done.
“Transplantation is a major decision. Complications increase and the risk of severe morbidity and mortality increases with age,” he said. “Patients may choose not to undergo a transplant for logistical, personal, or health reasons; they may not have insurance coverage or permission; Sometimes there are external factors, such as not being able to find a donor.”
“So there are many patient-centered reasons why patients may choose not to undergo a transplant when it is eligible and available,” he continued. “While this is improving over time, it is a sobering reminder that the majority of these patients ultimately cannot continue to do it.”
Pemaraju estimates that about 20% to 25% of patients will actually receive a transplant. “Can this metric improve over time?” he asked. “I think we can. Can we develop immunotherapies and other treatments that can cure the disease without a transplant? I hope so. We can come up with completely new platforms and approaches that can eradicate the disease before a transplant. Can we do that? This is also possible. These are the things we're working on in the lab and in early clinical trials, and that's exactly what we should be doing.”
disclosure
Pemaraju and Mesa had no relevant disclosures.
