S2 Episode 5: Posttransplant Monitoring in Myelofibrosis

Medscape

a day ago

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Tania Jain, MBBS: Hello everyone. We're back in our myelofibrosis for Medscape InDiscussion podcast. This is season two, and this is episode five, where we'll talk about transplant outcomes in myelofibrosis and how to address relapse post-transplant. I'm Tania Jain, and today we have our very special guest, Dr Rachel Salit, who is an associate professor at Fred Hutchinson Cancer Center and the University of Washington School of Medicine.
As a hematologist-oncologist, Dr Salit specializes in stem cell transplant, focusing on improving outcomes for patients with myeloproliferative neoplasms. Her research has included developing clinical trials to enhance and improve transplant success, prevent graft-vs-host disease (GVHD), and she also works on initiatives to support patients' return-to-work journeys post-transplant. Welcome, Dr Salit. It's an honor to have you.
Rachel Salit, MD: Thank you for having me today.
Jain: What we want to talk about today is pre-transplant, post-transplant, and how to think about transplant. I think we would all agree that transplant is presented and thought about differently, to some extent, by different clinicians and others who see patients in the clinic. What is your approach, and how do you go about telling patients about the role of transplant?
Salit: The way I approach patients with myelofibrosis is from two different sides. One is the scoring system criteria — going over the Dynamic International Prognostic Scoring System (DIPSS) and the Mutation-Enhanced International Prognostic Scoring System (MIPSS-70). That would include what their blood counts look like, their molecular profile, cytogenetics, whether they have any peripheral blasts, and whether we think they're at imminent danger for transforming to leukemia or needing blood or platelet transfusions.
The second side I look at with them is their life goals — what they are hoping for in terms of longevity vs quality of life.
I think we've made great strides in transplant in the last 10 years in myelofibrosis since the approval of Janus kinase (JAK) inhibitors. I talk with them about the role of JAK inhibitors in the pretransplant setting — whether they've had one or not — depending on their symptoms and splenomegaly, and how that affects transplant timing.
Ultimately, it's their choice. Patients often have strong opinions. There are patients with high-risk disease by scoring systems, but who are having a rather good quality of life and don't want to rush into treatment. Then there are patients with lower risk but who, because of younger age or life goals, want to proceed more expediently. I let the patient guide me.
The third component that goes into it is what our donor search looks like. I often don't know that when I first meet the patient, so I always add the caveat: This is the conversation we're having now, but once we assess sibling matches or unrelated donors, risks and benefits might change.
Jain: One of the things that challenges me is that there's a lot of prediction involved in the transplant decision, especially the first part you mentioned, about leukemia progression risk. There's no perfect metric to predict someone's transplant outcomes, whether for disease control, preventing relapse, or even nonrelapse mortality. How do you play the prediction game, without a crystal ball?
Salit: I think it is one of the most challenging aspects of myelofibrosis. I empathize with patients in that we consider this a somewhat elective procedure that no one wants to need. It's tougher on them than it is for acute myeloid leukemia (AML) patients, where we say, 'This is your option, and you need to do it now.'
For me, I try to look at the disease kinetics. When did it develop? How long has it been stable? If they have peripheral blasts in their blood, have they stayed at 1% for 2 years, or have they risen to 2% or 3%? Have their counts stayed stable? Is their spleen growing? Are their symptoms increasing?
If patients have poor-risk factors but stable disease, I'm less aggressive than I am with patients who have more benign features but rapidly progressing disease. Sometimes in younger patients, the disease progresses faster than expected, especially if they have just one high-risk mutation.
Jain: I always say that one of the most important things to follow is the trajectory of disease. When counts begin to drop or blasts start to appear, that makes you pause and think about transplant, or at least do a bone marrow biopsy to help make that decision.
I want to shift gears. I know you've been involved in defining remission post-transplant, which is a huge unmet need. Many disease features don't resolve quickly after transplant, yet we consider the transplant successful. The forms and shapes that remission or recurrence can take post-transplant have evolved. Can you share how you got involved in unifying the concept of remission post-transplant and what insights you can offer for our audience?
Salit: I got involved in this from two angles. Clinically, it's long been unsatisfying to tell patients post-transplant that they have low counts, persistent fibrosis, or splenomegaly when we discharge them from the acute transplant service at day 100.
The providers we discharge them to — often general oncologists — aren't always sure what to say. Are you in remission? How long will it last? How do we test for it?
The second part came from my work on the Medicare–Center for International Blood and Marrow Transplant Research (CIBMTR)) composite study, looking at whether transplant benefits patients over 55. We've been working on this for the past 7 years. When we met to define the response to transplant, we used the newly developed International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria for drug response in myelofibrosis, and we found that to be very complex for CIBMTR reporting. The people reviewing charts were not reporting consistently.
I was approached by Wael Saber from CIBMTR to help develop a consistent remission definition so that centers reporting outcomes — remission, persistent disease, or relapse — could be compared. We want to draw conclusions about what regimens and donors are working best.
We recognized that, unlike AML patients who go into transplant in CR1 (first complete remission), myelofibrosis patients go into transplant with active disease: persistent blasts, fibrosis, splenomegaly. We formed a committee of myelofibrosis transplant experts from the US and Europe. We wanted both CIBMTR and the European Society for Blood and Marrow Transplantation (EBMT) to have the same criteria so we could collaborate and combine data.
The strongest takeaway was that the main thing transplant can do that drugs currently cannot is put patients into molecular remission. Most patients have driver mutations — JAK2, CALR, MPL — and we know the majority clear these mutations post-transplant.
We recognized that patients with molecular remission may still have low counts or morphologic abnormalities. We classified these as subsets of molecular remission. We also agreed that persistent molecular abnormalities — especially if decreasing — shouldn't be considered relapse. Persistent disease can clear over time with rising CD3 chimerism and immune suppression taper.
We reserved 'relapse' for patients who had previously cleared their mutation and then redeveloped it. That's a much more concerning scenario requiring intervention.
Jain: That makes a lot of sense. One way I explain it to patients is that a transplant is an intervention with curative potential, but disease elimination takes time, even after donor hematopoiesis is established. It's not an immediate clinical remission — spleen and counts take time to improve. But once donor hematopoiesis is present, that can eventually trigger graft-vs-leukemia activity to eliminate residual disease.
Do you know if there's a difference in how CIBMTR and EBMT capture relapse?
Salit: I honestly don't know. But one of the goals of our project, with about six stakeholders from each registry, was to create a uniform definition. I think the recent New England Journal of Medicine paper by Gagelmann and colleagues spearheaded this molecular remission definition.
CIBMTR and Dr Saber are very enthusiastic about this, and I think we can develop reporting forms that consistently capture remission, persistent disease, and relapse as three categories.
We acknowledge there will be missing data. Not every center regularly tests molecular driver mutations. We've also discussed the role of chimerism. Fractionated chimerism is important, but most European centers don't assess it. They can do weekly molecular tests; we might test every 3 months at best.
So, blood counts and chimerism will still play a role. I've piloted this approach with my patients, and they find it more satisfying. At day 100, I can say, 'You still have fibrosis, splenomegaly, and low platelets — but your JAK2 is negative. We're considering this remission.' That's much more reassuring for them than wondering why we even did the transplant.
Jain: I totally agree. Bringing together the American and European efforts — making them globally unified — would be a huge advancement in research. Right now, it's hard to use or compare registry data across systems since it's not apples to apples.
You mentioned you're already using this with your patients. There are times when spleen, fibrosis, or counts aren't fully normalized. Can you share your approach for relapse or 'impending relapse' when you see persistent disease features like cytopenias, transfusion needs, splenomegaly, dropping chimerism, or persistent molecular mutations?
Salit: We check molecular driver mutations every 3 months — at months 3, 6, 9, and 12. If the 3-month result is negative but the patient still has low CD3 chimerism, needs transfusions, or has fibrosis, we start tapering immune suppression at day 100.
We follow chimerism monthly during tapering. If it's not at 100% by 6 months, we may do a bone marrow biopsy to see if anything concerning is present.
If the mutation's variable allele frequency is decreasing, that's reassuring. If it's back and chimerism is dropping — say it was 100% at day 100 and 90% at 6 months — we consider donor lymphocyte infusion (DLI), assuming they're off immune suppression and don't have GVHD. If they're still on immune suppression, we taper conservatively and wait a month before giving DLI.
We only use therapy like hypomethylating agents and JAK inhibitors if blasts return in the peripheral blood or marrow, or if abnormal cytogenetics reappear.
Jain: Those are tough situations — when blasts are visible, or disease features reappear. How often do you consider a second transplant in myelofibrosis?
Salit: Not often. Thankfully, we're seeing only 5%-10% relapse rates. At our center, we're still doing relatively mild ablative transplants: Cytoxan/busulfan for those under 60, or decitabine/melphalan for those over 60.
If a patient completely loses CD34 or CD33 chimerism, we consider a second transplant. There's concern that giving DLI in that setting could cause aplasia. If the disease burden is too high, we go straight to the second transplant.
Jain: That makes sense. Well, this was phenomenal. Thinking about transplant is a nuanced process, and we loved hearing your thoughts. We look forward to reading about the remission definitions post-transplant and implementing them in the clinic.
On behalf of our audience, thank you so much for your time. That concludes episode 5 on transplant outcomes in myelofibrosis. We'll see you in the next episode.
Listen to additional seasons of this podcast.
Primary Myelofibrosis
Role of Hematopoietic Stem Cell Transplantation in Patients With Myeloproliferative Disease
Decreasing Chronic Graft-Versus-Host Disease Rates in All Populations
Diagnosis and Evaluation of Prognosis of Myelofibrosis: A British Society for Haematology Guideline
Prognostic Value of Blasts in Peripheral Blood in Myelofibrosis in the Ruxolitinib Era
Acute Myeloid Leukemia (AML)
CIBMTR Myelofibrosis Medicare Study
Proposals for Revised International Working Group-European LeukemiaNet Criteria for Anemia Response in Myelofibrosis
Utility of Assessing CD3+ Cell Chimerism Within the First Months After Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia
Clearance of Driver Mutations After Transplantation for Myelofibrosis
Donor Lymphocyte Infusion and Molecular Monitoring for Relapsed Myelofibrosis After Hematopoietic Cell Transplantation
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Cite this: Posttransplant Monitoring in Myelofibrosis - Medscape - Jun 10, 2025.