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Splenectomy Versus Other Therapy in ITP

Panelists: Ivy Altomare, MD, Duke University Medical Center; Terry Gernsheimer, MD, Fred Hutchingson Cancer Research Center; Keith R McCrae, MD, The Cleveland Clinic
Published: Tuesday, Feb 20, 2018



Transcript: 

Ivy Altomare, MD: What are the pros and cons of being on a continuous therapy, versus just doing spurts of treatment, as you would with steroids or Rituxan (rituximab)? It’s kind of a difficult question.

Keith R. McCrae, MD: I don’t think there’s any pros or cons, per se. I think it’s more of an issue of, what are the toxicities of the particular agents? I will say, I have college-aged patients who really don’t want to take a pill every day. They may drink a beer or 2 and forget to take it, or something. But, they just don’t want to be sick. They feel that they’re infallible. Some of those patients even think about splenectomy, sometimes. But, on the other hand, for most people, getting a shot a week, or a pill a day, is not a big deal.

Terry Gernsheimer, MD: I’m glad you actually brought that up. I had a college student. Early on, she was put on romiplostim. She did beautifully with the drug. We almost got her tapered off. Then, she needed a small dose to maintain her. But, college students like to travel. They like to take courses in other countries. And so, first she went to Australia. She said, “What am I going to do about my drug?” And I said, “I have colleagues in Australia.” So, we gave her those names and they took care of her. Then, she emailed me and said, “Now I want to go to New Zealand.” I said, “Well, I do know somebody in New Zealand.” So, we got that done. Then, she went to Greece. I did know somebody in Greece but, at that point, I said, “You know what, it’s time to think about something else.”

Ivy Altomare, MD: What dedication.

Terry Gernsheimer, MD: Yes, it was. She went on to splenectomy. That was 5 years ago, and she’s still in remission. That was a young college student. So, it’s a great story. I just recently had a patient who wanted to go to Paris. She’s getting romiplostim and I had to find somebody for her. So, it is difficult.

Ivy Altomare, MD: Yes, but when you’re on a drug that works, it’s hard to walk away from that, especially if you know that this is a lifetime disease.

Terry Gernsheimer, MD: Exactly.

Ivy Altomare, MD: So, splenectomy has been mentioned, and it is certainly a tried and true effective way to manage second-line ITP, and beyond. Let’s talk about the rates of remission with splenectomy. What are the response rates? How are you using splenectomy in clinical practice, when there are these other agents that are effective and you don’t have to remove part of your body?

Keith R. McCrae, MD: Well, that’s exactly the thing that bothers people.

Ivy Altomare, MD: Yes.

Keith R. McCrae, MD: But, splenectomy is the single approach that gives the longest complete response rate of anything we can do for idiopathic thrombocytopenia purpura. It’s always been that way, and it still is. From that point of view, it’s a good treatment. The biggest problem with splenectomy, in my mind, is that you cannot, no matter what, predict who will respond and who will not. Patients do not like to say, “Well, I don’t want to have surgery and not know that it’s going to work. It’s not like you’re taking my appendix out or something.” And so, that’s the major downside. There are other things available. You can take a pill or whatever, and see if it works or not. Then, maybe go to splenectomy?

I do think splenectomy has long-term consequences. There is an increased risk of infection. Personally, I think that’s overblown in this era of vaccinations, and better vaccinations and awareness. There is some suggestion, that I think is true, that these patients have a very slight increased long-term risk of venous thrombosis over many, many years. But, it’s a slight risk. It’s probably less than that of a Factor V Leiden. It may be significantly less.

I think the long-term risks of splenectomy are somewhat overblown. Still, I’ve not had many patients go to splenectomy. I rarely do these days, because there are other options. People don’t like to have surgery without a guarantee.

Ivy Altomare, MD: Right. So, what about other agents or combinations that can be used in the highly, highly refractory patient who has been exposed to steroids, and IVIG [intravenous immunoglobulin], and TPO [thrombopoietin] mimetics? Maybe they have had their spleen out, and gotten several courses of Rituxan? For some reason, all of these patients are in my practice.

Terry Gernsheimer, MD: A few of them are in mine. Not all of them are in yours.

Ivy Altomare, MD: Specifically, other immunosuppressants, and maybe even cytotoxics?

Terry Gernsheimer, MD: This is one of the reasons why I’m always a little nervous about splenectomy. First of all, the patients are worried that it’s not going to work. I’m always worried that I’m going to have to use something cytotoxic, or something very immunosuppressive. “Now, I have a patient with no spleen. I’m going to have to use that.”

I think there are a lot of other immunosuppressives that can be very helpful. I’ve had very good luck with mycophenolate. I think other T-cell suppressing agents can be very good, like sirolimus, which, by increasing Tregs [regulatory T-cells], that may be how that’s working. It’s kind of exciting to think about that.

I’ve always liked azathioprine for steroid sparing, if I can’t use other agents. We wrote a paper years ago on using pulse cyclophosphamide. This was not the daily dose cyclophosphamide, which really does increase the risk of leukemia, down the line, if you do that long-term. But, we gave 2 doses of a gram per meter squared. It’s pretty much the typical dose that is used for patients who have antibodies, for example, to Factor VIII. For example, spontaneous, without rituximab. But, in that circumstance, they use rituximab. There’s no data to suggest that it works better, but we had very good response rates doing that. Those were very refractory patients. That’s why we did it. They had failed splenectomy. Now, we have other things. But generally, when I sit down with a patient, I show them the whole gamut.

Ivy Altomare, MD: Right.

Terry Gernsheimer, MD: They almost always say, “Well, I don’t want to take those chemotherapy immunosuppressive things.” But sometimes, we eventually get to mycophenolate or to cyclophosphamide.

Ivy Altomare, MD: Sure, absolutely.

Terry Gernsheimer, MD: And it’s nice to know that’s out there. But, all of those are going to add to the problem, especially if they’ve been splenectomized, of worrying about whether or not they may have an opportunistic infection.

Ivy Altomare, MD: Right. They’re toxic and they’re difficult to take. The patients are sick, at this point, anyway.

Transcript Edited for Clarity 

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Transcript: 

Ivy Altomare, MD: What are the pros and cons of being on a continuous therapy, versus just doing spurts of treatment, as you would with steroids or Rituxan (rituximab)? It’s kind of a difficult question.

Keith R. McCrae, MD: I don’t think there’s any pros or cons, per se. I think it’s more of an issue of, what are the toxicities of the particular agents? I will say, I have college-aged patients who really don’t want to take a pill every day. They may drink a beer or 2 and forget to take it, or something. But, they just don’t want to be sick. They feel that they’re infallible. Some of those patients even think about splenectomy, sometimes. But, on the other hand, for most people, getting a shot a week, or a pill a day, is not a big deal.

Terry Gernsheimer, MD: I’m glad you actually brought that up. I had a college student. Early on, she was put on romiplostim. She did beautifully with the drug. We almost got her tapered off. Then, she needed a small dose to maintain her. But, college students like to travel. They like to take courses in other countries. And so, first she went to Australia. She said, “What am I going to do about my drug?” And I said, “I have colleagues in Australia.” So, we gave her those names and they took care of her. Then, she emailed me and said, “Now I want to go to New Zealand.” I said, “Well, I do know somebody in New Zealand.” So, we got that done. Then, she went to Greece. I did know somebody in Greece but, at that point, I said, “You know what, it’s time to think about something else.”

Ivy Altomare, MD: What dedication.

Terry Gernsheimer, MD: Yes, it was. She went on to splenectomy. That was 5 years ago, and she’s still in remission. That was a young college student. So, it’s a great story. I just recently had a patient who wanted to go to Paris. She’s getting romiplostim and I had to find somebody for her. So, it is difficult.

Ivy Altomare, MD: Yes, but when you’re on a drug that works, it’s hard to walk away from that, especially if you know that this is a lifetime disease.

Terry Gernsheimer, MD: Exactly.

Ivy Altomare, MD: So, splenectomy has been mentioned, and it is certainly a tried and true effective way to manage second-line ITP, and beyond. Let’s talk about the rates of remission with splenectomy. What are the response rates? How are you using splenectomy in clinical practice, when there are these other agents that are effective and you don’t have to remove part of your body?

Keith R. McCrae, MD: Well, that’s exactly the thing that bothers people.

Ivy Altomare, MD: Yes.

Keith R. McCrae, MD: But, splenectomy is the single approach that gives the longest complete response rate of anything we can do for idiopathic thrombocytopenia purpura. It’s always been that way, and it still is. From that point of view, it’s a good treatment. The biggest problem with splenectomy, in my mind, is that you cannot, no matter what, predict who will respond and who will not. Patients do not like to say, “Well, I don’t want to have surgery and not know that it’s going to work. It’s not like you’re taking my appendix out or something.” And so, that’s the major downside. There are other things available. You can take a pill or whatever, and see if it works or not. Then, maybe go to splenectomy?

I do think splenectomy has long-term consequences. There is an increased risk of infection. Personally, I think that’s overblown in this era of vaccinations, and better vaccinations and awareness. There is some suggestion, that I think is true, that these patients have a very slight increased long-term risk of venous thrombosis over many, many years. But, it’s a slight risk. It’s probably less than that of a Factor V Leiden. It may be significantly less.

I think the long-term risks of splenectomy are somewhat overblown. Still, I’ve not had many patients go to splenectomy. I rarely do these days, because there are other options. People don’t like to have surgery without a guarantee.

Ivy Altomare, MD: Right. So, what about other agents or combinations that can be used in the highly, highly refractory patient who has been exposed to steroids, and IVIG [intravenous immunoglobulin], and TPO [thrombopoietin] mimetics? Maybe they have had their spleen out, and gotten several courses of Rituxan? For some reason, all of these patients are in my practice.

Terry Gernsheimer, MD: A few of them are in mine. Not all of them are in yours.

Ivy Altomare, MD: Specifically, other immunosuppressants, and maybe even cytotoxics?

Terry Gernsheimer, MD: This is one of the reasons why I’m always a little nervous about splenectomy. First of all, the patients are worried that it’s not going to work. I’m always worried that I’m going to have to use something cytotoxic, or something very immunosuppressive. “Now, I have a patient with no spleen. I’m going to have to use that.”

I think there are a lot of other immunosuppressives that can be very helpful. I’ve had very good luck with mycophenolate. I think other T-cell suppressing agents can be very good, like sirolimus, which, by increasing Tregs [regulatory T-cells], that may be how that’s working. It’s kind of exciting to think about that.

I’ve always liked azathioprine for steroid sparing, if I can’t use other agents. We wrote a paper years ago on using pulse cyclophosphamide. This was not the daily dose cyclophosphamide, which really does increase the risk of leukemia, down the line, if you do that long-term. But, we gave 2 doses of a gram per meter squared. It’s pretty much the typical dose that is used for patients who have antibodies, for example, to Factor VIII. For example, spontaneous, without rituximab. But, in that circumstance, they use rituximab. There’s no data to suggest that it works better, but we had very good response rates doing that. Those were very refractory patients. That’s why we did it. They had failed splenectomy. Now, we have other things. But generally, when I sit down with a patient, I show them the whole gamut.

Ivy Altomare, MD: Right.

Terry Gernsheimer, MD: They almost always say, “Well, I don’t want to take those chemotherapy immunosuppressive things.” But sometimes, we eventually get to mycophenolate or to cyclophosphamide.

Ivy Altomare, MD: Sure, absolutely.

Terry Gernsheimer, MD: And it’s nice to know that’s out there. But, all of those are going to add to the problem, especially if they’ve been splenectomized, of worrying about whether or not they may have an opportunistic infection.

Ivy Altomare, MD: Right. They’re toxic and they’re difficult to take. The patients are sick, at this point, anyway.

Transcript Edited for Clarity 
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