Jason Gotlib, MD, MS
	Associate Professor of Medicine (Hematology) Stanford University School of Medicine/Stanford Cancer Institute Stanford, California

At Stanford the upper cutoff for a full allotransplant is age 55 to 60 years. An example of a situation in which I would recommend an allotransplant would be for a 55-year-old patient with intermediate-2 or high-risk MF who has a good performance status. Because they have intermediate-2 or high-risk disease, they would likely have a short-term higher mortality than potentially that provided by even a full transplant.

	Elias Jabbour, MD
	Associate Professor Leukemia Department The University of Texas MD Anderson Cancer Center Houston, Texas

An example of a patient for whom I would recommend an allotransplant would be a fit 50-year-old patient I saw in my practice. He had some fatigue, bone aches, pruritus and a big spleen. He had MF, for which I recommended ruxolitinib, which he received for 6 months to a year.

However, this patient did not respond well to ruxolitinib and his spleen remained large. I identified a donor for him and stopped therapy, and he underwent transplant followed by a splenectomy. It is not always the case that after transplantation the patient’s MF will be gone, especially the fibrosis.

	Jerry L Spivak, MD
	Professor of Medicine and Oncology Director, The Johns Hopkins Center for the Chronic Myeloproliferative Disorders Johns Hopkins University School of Medicine Baltimore, Maryland

Patients who respond best to transplantation are those who are young and have good-stage disease. Transplantation is in flux now because there is the option of reduced-intensity conditioning. But if I had a young person with bad disease, I would recommend transplantation, preferably an allotransplant.

By younger, I mean anyone younger than 60 years of age. Bad-stage disease would refer to a patient with complex cytogenetics with more than one mutation. I always order cytogenetic testing, and mutations override the stage of the disease in my opinion. Mutations such as deletion 5, 5q, 7, 7q, 12p and 17p would make me consider transplantation, even for a patient with low-stage disease. Those are tough decisions to make, particularly if the patient is feeling well. If the patient has a good sibling match, the transplant-weighted mortality is low enough now to make it a worthwhile treatment approach.

	Moshe Talpaz, MD
	Alexander J Trotman Professor of Leukemia Research Associate Director of Translational Research UM Comprehensive Cancer Center Associate Chief, Division of Hematology/Oncology Director, Hematologic Malignancies University of Michigan Medical Center Ann Arbor, Michigan

First, the patient has to be resistant to JAK2 inhibitors. This means that the patient received a JAK2 inhibitor and either benefitted from that therapy and stopped responding or never responded. This is the first parameter. The second is age. We go up to age 70, but most of the patients who undergo transplant are younger than that. The third parameter is that the patient must have IPSS intermediate/high scores or intermediate-2 or high-risk disease. We will not recommend transplantation for a patient with low-risk disease, which means that the outlook of the patient is good. The outlook for survival without the transplant is 2 years or less for patients with intermediate-2 or high-risk MF. Based on these parameters, we will decide whether to recommend transplantation or administer experimental therapies.

We have not included mutations as a parameter. Of course, there are high- and low-risk mutations, but then you’re talking more about DIPSS or the parameters from the Mayo Clinic. These are not included in our calculations.

Allogeneic bone marrow transplantation is probably performed increasingly in MF. Its limitation is that it is associated with significant risks, particularly in this disease. Considering the fact that MF is much more frequent in the aged population, many of the patients are not eligible for transplant. Our experience is fairly limited. We don’t have studies of hundreds of patients. We have studies of a few dozen patients who have undergone transplantation. It is curative, but there are issues of graft failure, graft rejection, graft versus host disease and slow hematopoietic recovery, which is probably more significant in this disease than in other transplants. At this stage, the overall outcome is not as good as the outcomes in other diseases subjected to allogeneic bone marrow transplantation.

	Srdan Verstovsek, MD, PhD
	Professor of Medicine Chief, Section for Myeloproliferative Neoplasms (MPNs) Department of Leukemia Director, Clinical Research Center for MPNs The University of Texas MD Anderson Cancer Center Houston, Texas

IPSS and DIPSS are important assessment tools to decide on the timing of a transplant because they give you relatively good assessments of survival. These survival assessments have never been used to direct medical therapy other than transplant in common practice. But they are important to do because transplant is the curative attempt and it needs to be attempted when the time comes.

Traditionally, patients with intermediate-2 or high-risk disease, according to IPSS or DIPSS, are those with a short life expectancy, 2 years for patients with high-risk disease and 4 years for those with intermediate-2 risk disease. These patients would be candidates for bone marrow transplant. We would discuss this up front as a possibility and refer the patient for transplantation to see whether he/she would be a good candidate after evaluation and if there is a donor. The patients with earlier-stage and low-risk disease have an average survival beyond 10 years, so transplantation is not recommended for these patients.

Because we are an academic center, we will perform transplants for patients up to age 75 years. I believe that most of the community-based doctors perform transplants for patients aged 55 to 60 years. The number of patients who undergo transplant is low. Here, it’s less than 10%. Although we see about 250 new patient referrals with MF every year, we still have few patients going for a transplant, even when they have a donor.

The question exists as to the role of mutations in determining whether a patient will undergo transplantation. This is a particularly important question for those patients with early-stage disease by IPSS or DIPSS criteria but with aggressive disease based on presence of a mutation. Dr Vannuchi from Italy presented data at ASH 2012 evaluating the most common mutations in about 500 patients with MF and found 3 mutations that would identify patients at high risk of early death or transformation to acute myeloleukemia. Exploratory research such as this is being done but is not an everyday practice.