When Should You Employ Transplantation in Myelofibrosis Therapy?

If there is a clear indication for stem cell transplantation, a patient with myelofibrosis should be referred to the transplantation team as soon as possible, according to Nicolaus Kröger, MD.

In a conversation with CancerNetwork^®, Kröger broke down the current myelofibrosis treatment landscape as it related to the use of stem cell transplantation. He spoke in the context of a presentation he gave at the Seventh Annual Miami Cancer Institute Immunotherapies Summit for Hematologic Malignancies outlining the appropriate circumstances for transplantation in this patient population.

Kröger described how factors such as life expectancy, donor availability, age, comorbidities, and other disease-specific factors impact the likelihood of a patient needing to undergo transplantation for myelofibrosis. Additionally, he spoke to the efficacy of new JAK inhibitors and other therapeutic strategies that may synergize well with transplantation. Although it once represented a “neglected” field in the hematologic oncology community, myelofibrosis management is now experiencing rapid movement with the advent of these novel agents.

“The key point should be that for myelofibrosis and for other diseases, the transplant physician should be involved early on. The transplant is not [for] everybody, but if I see a patient early on, and there’s still no indication, they will be sent back to the physician [for transplantation],” Kröger stated. “All patients who have a potential indication for transplant, even many years later…should be involved with the transplanter. This is something that I hope [for] because my feeling is that in many hematological diseases, we still, in many patients, miss the optimal time point to go for transplantation.”

Kröger is the medical director of the Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, as well as a professor of Medicine at the University of Hamburg.

CancerNetwork: What is the background of your presentation, “Myelofibrosis: Who to Transplant and Who Not to Transplant?”

Kröger: The main question here at this [meeting] was to convince the majority of hematologists to send patients to transplantation if there is a clear indication for stem cell transplantation. Myelofibrosis is, as many hematological diseases, a rare disease, but allogeneic stem cell transplantation is currently the only curative treatment approach. For many years, this disease was a bit neglected in the hematological community because they thought [the disease] lives forever. But this is not true. It’s a very heterogeneous disease. You have patients with survival of fewer than 2 years, but you also have patients with survival of more than 20 years.

Over the last 10 to 20 years, several so-called risk scores have been developed so you can distinguish patients with shorter and longer life expectancies. In my presentation, [I discussed]....which patients are too early to go for transplant, and for which patients is transplant not a good option because they are too old or for [other] reasons. I went into different scoring systems because, at the end, transplantation is a bit more difficult than in acute leukemia, for instance, or myelodysplastic syndrome [MDS]. These patients have fibrosis, meaning that the bone marrow is fibrotic. The bone marrow is the microenvironment for new stem cells. For the stem cells, which need to find their niche, if you have such an unpleasant microenvironment, it’s difficult to get what we call engraftment. The second reason is these patients usually have a huge spleen, which also impacts engraftment and complication [after] transplantation. Therefore, for many years, even if it was a curative treatment approach, transplanters were very curious or reluctant to go for transplantation. At least 20 years ago, in our European registry, only 50 patients had been transplanted. Now, in the US and in Europe, it’s about more than 500 [transplants] per year.

Based on your presentation, what clinical and patient characteristics influence your decision to use transplantation as part of a patient’s treatment plan?

If the patient has a life expectancy of less of 5 years, this can be an indication for transplantation, and the patient should be sent to a transplanter who should evaluate the eligibility for stem cell transplantation. In reality, the story is more complicated because this is [unlike] other hematological diseases; it is a clonal evolution. Even patients who have a good risk factor today might have bad risk factors in 2 or 3 years, so those patients need to be followed. At the end, we have patients who need an immediate transplant, and patients should be followed and receive the transplant only if they are progressing.

What I also showed is that the indication, historically, is mainly based on disease-specific factors. If you have a bad disease, you should go for transplantation. However, in the transplant field, you also have risk factors, that means we should also consider transplant-specific risk factors. One example, for instance, in myelofibrosis is the donor availability, or the HLA. If there is only a mismatched donor, then the outcome is much worse than if there are completely matched donors, which is different nowadays in comparison with acute myeloid leukemia, for instance. These are things that you must take into this decision model, or decision-finding, together with the patients. You need to clear a good consultant to counsel the patient about the risk of the disease, but also the risk of the transplant, and then come up with a common decision to go immediately for transplant, later to transplant, or [to avoid] transplant.

What populations of patients should avoid transplantation for the management of myelofibrosis?

Usually, you [perform] the transplant only if you want to cure the patients; that means the disease is gone. But there’s some inherited risk of transplantation. Therefore, you should always look at the life expectancy of these patients with the disease and if the patient wouldn’t have the disease [with treatment]. That means 80-year-old patients who have a life expectancy of 4 to 5 years are not candidates for transplantation because the median life expectancy of these patients in a general population is not higher than 80 years.

Age, comorbidities, and the donor availability are also issues. It’s a complex issue. We have developed some scores that we can discuss with the patients and to come up with a common decision to go for transplant or not.

What can be done to improve the overall efficacy of transplantation across this myelofibrosis population? Are there any novel agents or therapeutic strategies that may work in tandem with transplantation?

It’s quite easy in transplantation because you [perform] it for cure. If you see all patients with myelofibrosis, the cure rate is about 65% to 70% of these patients can be cured. About 30% will [progress on] transplant. There are only 2 reasons for [progression]. One is relapse, which is the most frequent [in] about 20% [of patients]. The other is complications, non-relapse mortality because of infection, and other complications like graft-versus-host disease. It depends a bit on the center experience because it’s a quite complicated treatment.

In good centers, about 10% to 15% [see] this risk of non-relapse mortality. All the efforts we have done now in the last 20 years were to reduce the risk of non-relapse mortality and reduce the risk of relapse. Some examples [include] the spleen size, which is very huge, or graft-versus-host disease. Here, for instance, the JAK inhibitors are quite useful. With JAK inhibitors, you can reduce the spleen size before transplantation. We and others have shown that if you reduce [the spleen] size before transplantation, outcomes are much better, especially if patients are still responding to JAK inhibitors. If patients are on JAK inhibitors and [progress]…then outcomes become worse. If there’s an indication for transplant, we put patients on JAK inhibitors; if the patient is responding, they should receive the transplant. JAK inhibitors are now essential in preparing the patient for transplant.

More recent data [indicate] to continue with the JAK inhibitors through the transplant. We call this peritransplant. Because some of the JAK inhibitors are approved for steroid refractory graft-versus-host disease, we and others have shown that if you continue the JAK inhibitors through the transplant, you can improve engraftment, surprisingly. You can also reduce graft-versus-host disease as one of the complications. Therefore, the idea is not to [say] one is better than the other; it’s to include all the effective drugs or approaches in one common strategy, to combine JAK inhibitors with transplantation.

If JAK inhibitors are not working for the spleen size, which can happen, there are other options. Historically, many centers did a splenectomy before the transplant, but this is quite complicated and still associated with morbidity and mortality. Just one of the recent developments is to use spleen aeration. Spleen aeration is usually associated with cytopenia, but if you do it immediately before transplantation and before you start conditioning, then you don’t care about the cytopenic effect. This is working quite effectively because the median spleen size reduction is about 5 cm if you include the spleen aeration before transplantation.

The other issue is the relapse. Patients [may] have so-called driver mutations, either JAK2, MPL, or CALR. [Additionally], 90% are harboring these mutations. With sensitive pCR, you can monitor patients after transplant [to see] whether they still have residual disease, even if they are otherwise fine. Then, you can modulate the immune system by reducing immunosuppression or giving donor lymphocyte infusion to treat what we call minimal residual disease in order to cure the patients. We and others have shown if you still have minimal residual disease after transplant, then the risk of relapse is higher.

What are some key considerations [in] monitoring for potential toxicities that may occur during transplantation? How can clinicians help ensure safe transplantation and protect patient quality of life?

What I personally learned in the last 30 years is that what we call the post-transplant period is very important. Clinically speaking, in these 4 weeks when the patient is inpatient, when you have a lot of physician nurses taking care of the patients, this is nothing else but putting a new immune hematological system in the patients. Once the system is in the patient and [they are] discharged at home, they have a new immune system from the donor, and this can cause complications, which we call graft-versus-host disease. It can also cause a graft-versus-myelofibrosis effect. At the end, it’s a new immune system that is killing the myelofibrosis cells. Therefore, this post-transplant period in the first 6 months is very crucial. We recommend that this patient should stay at least with the transplant physician where they were transplanted to work with this immune system in order to reduce the risk of relapse, the risk of complications, and therefore the risk of non-relapse mortality.

Looking ahead, how do you hope to see the myelofibrosis field evolve with respect to improving outcomes among patients?

The good thing is because [myelofibrosis] was, for many years, a neglected disease, even for hematological physicians and private practices, everybody has these patients. Myelofibrosis is actually the worst disease. Polycythemia vera and essential thrombocythemia [are] much [easier to manage]. But because we have drugs in this field like JAK inhibitors and new drugs like BET inhibitors and interferon, there is now more interest for looking at the [disease] biology and treatment. This is a good sign for all patients. If we have more interest from the physicians, the researchers, and the industry, it will benefit the patients in the end. Therefore, the field is rapidly moving in myeloproliferative neoplasms [MPNs] and in myelofibrosis.

We have several issues; maybe we should go back from primary end points of spleen size reductions to progression-free survival and so on. But the field is rapidly moving. We have novel agents, and they look quite promising.

Reference

Kröger N. Myelofibrosis: who to transplant and who not to transplant? Presented at the Seventh Annual Miami Cancer Institute Immunotherapies Summit for Hematologic Malignancies; March 6-7, 2026. Miami, FL.