Global Expert Perspectives on Managing Excess Iron - Episode 5

Stem Cell Transplantation in Patients with MDS

Transcript:Vinod Pullarkat, MD: Allogeneic stem cell transplant is the only transplant until now that has curative potential in MDS. So, every MDS patient who is a suitable candidate should at least have a transplant evaluation at a stem cell transplant center. There are various factors that are considered when you decide to go ahead with transplantation. One, obviously, is the risk category of the patient: how likely is this patient going to transform into AML? For example, for the low- and intermediate 1-risk patients, the practice is to wait and transplant them when they have disease progression. That is because there is significant amount of nonrelapse mortality associated with transplant. And MDS patients, they’re older patients and they have significant comorbidities, which will have to be considered when you make that decision. The availability of a donor is another consideration: how closely matched is the donor that is available? So, all of these factors—patient comorbidity, the donor availability, the risk of the patient—will have to be considered when you make that decision to move forward with transplant. Age, by itself, is not an absolute criteria. There are patients who may be in their 70s who may be appropriate candidates, although, as you get older, the outcomes of transplant are worse.

Heather Leitch, MD, PhD: Stem cell transplantation is the only potentially curative therapy for MDS. But, of course, it has a high morbidity and transplant-related mortality. And like everything we do in medicine, we want to weigh the potential risks against the potential benefits. So, a number of factors are taken into account when assessing a patient’s eligibility for stem cell transplantation, including age, donor status, performance status, and comorbidities. Depending on these factors, the patient may or may not be a candidate for stem cell transplantation.

In MDS, lower-risk patients may have a good quality of life for long periods of time before they progress to higher-risk MDS. And so, doing a stem cell transplant up front may not be in their interest. In higher-risk patients, however, they do have a high mortality, and so, doing a stem cell transplant earlier is probably better. This has been demonstrated in a decision analysis by Corey Cutler and his colleagues, not only the original decision analysis in the days of the IPSS, but also a more recent one in the days of some of the newer treatments for MDS.

Vinod Pullarkat, MD: The degree of iron overload is an important consideration in patients who are proceeding to stem cell transplantation. Various studies, mostly retrospective, have shown that patients who come into transplant with high levels of body iron do have a poor outcome for a variety of different reasons or causes. For the approach to a patient who is proceeding to transplant, the first and foremost is to prevent iron overload by monitoring that patient and using chelation appropriately. And this is particularly an issue with the lower risk patients who may be seen or may be transfusion-dependent for a while before they proceed to transplant. Unfortunately, the chelators will take some time to bring the body iron burden down, so they often—when patients are seen at the transplant center—are in need of immediate transplant and there is not enough time to chelate them.

But in a patient whose risk of transformation is low and transplant is needed, one can chelate the patient adequately before proceeding to transplant. One example would be a lower-risk patient who is transfusion-dependent and needs a stem cell transplant. In high-risk patients, it’s not often possible to chelate them prior to transplant. We do know that the non-transferrin—bound iron in the plasma rises during the transplantation, and that is implicated in many of the complications of stem cell transplant. But we don’t have a good treatment for that during transplant, so we will have to deal with the iron overload after they are done with the transplant. We can be careful during transplantation. We know that iron overloaded patients have certain risks, particularly risks for complications like infections or veno-occlusive disease. So, it allows us to be aware of these risks and manage those patients appropriately.

For the management of iron overload after transplant, there are no good studies which compare different approaches. Basically, there are two ways you can deal with it. One is by phlebotomy. The other one is using a pharmacologic approach, which is iron chelation. In patients who have good graft function—they have normal hemoglobin after transplant—you can phlebotomize those patients. If the venous access is good, they can be phlebotomized and you can bring iron burden down that way. It is not clear if pharmacologic chelation is better than phlebotomy. It is easier in some ways for the patient. But there are oral iron chelators. Most often used is deferasirox, which has some side effects which may make it difficult to administer it in the posttransplant period. For example, the gastrointestinal toxicity of the drug or the renal toxicity of the drug may be a problem when it’s given with some of the other medications that are given after transplantation. These two approaches are possible after transplant, either phlebotomy or by oral iron chelation using deferasirox, and there is no definite answer for that. A lot of factors are considered before we make that decision.

Heather Leitch, MD, PhD: Managing iron overload after transplantation is a much easier management situation than before or during transplant. And we have two options for iron reduction post stem cell transplant. For patients who have no transfusion requirement post transplant, and who have a relatively normal hemoglobin, phlebotomy intermittently may be a good option for reducing iron overload over time. For other patients, iron chelation therapy may be warranted; for example, if they’re not yet transfusion-independent, haven’t fully engrafted. With iron chelation therapy, we do get a suppression of labile plasma iron. So, theoretically, it may be better than intermittent phlebotomy, but I think this still needs to be demonstrated by clinical trials.

Transcript Edited for Clarity