Chapter: 12 Key Studies of Infection in Leukemia Patients
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Description
Dr. Bodey begins by observing that in the sixties the antibiotic genomycin was commonly used but was not effective against infections in neutropenic patients. He talks about the studies he did when carbenicillan became available. He conducted the first study of carbenicillan’s effectiveness against pseudomonas, finding a 91% cure rate and dramatically influencing the survival rate for leukemia patients.
Next Dr. Bodey talks about a definitive study he conducted while working with Dr. J Freireich at the NCI in Bestheda: Quantitative Relationships Between Circulating Leukocytes and Infection in Patients with Acute Leukemia. He describes the importance of this paper, which established findings he would build on once he came to MD Anderson. Dr. Bodey explains why MD Anderson could support large scale studies.
Dr. Bodey next talks about how Developmental Therapeutics conducted studies of chemotherapy using new drugs and new combinations. He reflects on the philosophical differences Developmental Therapeutics and the Division of Medicine over using aggressive experimental protocols on patients.
[Note: The recorder is paused]
Identifier
BodeyGP_03_20130723_C12
Publication Date
7-23-2013
City
Houston, Texas
Interview Session
Gerald P. Bodey Sr., MD, Oral History Interview, July 23, 2013
Topics Covered
The Interview Subject's Story - The Researcher The Researcher MD Anderson History Building/Transforming the Institution Multi-disciplinary Approaches Career and Accomplishments MD Anderson Impact Discovery and Success MD Anderson Culture Institutional Politics The Researcher The History of Health Care, Patient Care Professional Practice The Professional at Work Overview Definitions, Explanations, Translations Patients Patients, Treatment, Survivors Definitions, Explanations, Translations Discovery and Success Industry Partnerships Understanding Cancer, the History of Science, Cancer Research On Research and Researchers Controversy
Transcript
Gerald P. Bodey Sr., MD:
Well, it was. And that was one of my early interests was in treating infections in cancer patients. One of the first drugs that became available at that time that looked promising was an aminoglycoside antibiotic called gentamicin. People were enthusiastic about this drug, because it had a broader spectrum of activity than the other aminoglycosides and other antibiotics. It was a pretty special incorporation. It looked like it was going to be a very useful drug. We did some studies with it also, but what we found, to our dismay, was that it really wasn’t very effective in people who were neutropenic. If they didn’t have neutrophils, they didn’t respond. And if they did, then yes, it had a much better spectrum of activity than the existing antibiotics at that time. But we then—another antibiotic became available known as carbenicillin, which was a penicillin. It was produced by Beecham Laboratories in England. I was able to contact their medical director here in the United States and interest him in doing studies in our leukemic patients. Well, the daily dose of carbenicillin was thirty grams. That’s a lot of drug. And it was supplied in one-gram vials. So we would get big barrels of this drug shipped to us from England, filled with carbenicillin. As we went along and were using more and more of this drug, we ended up at one point having one nurse who was coming in and all she was doing was mixing carbenicillin all day to give to the patients. But it really was a major improvement, particularly in Pseudomonas infections. At that point in time, Pseudomonas was becoming a major problem in our neutropenic patients. I mean, if they got that, they were going to die, because the only other antibiotic that had activity was gentamicin, and it didn’t work if you didn’t have any neutrophils. The carbenicillin did, and it really made a huge difference.
Tacey Ann Rosolowski, PhD:
Can I ask you, Dr. Bodey, how did you discover these different drugs? Were you always on the lookout for what was new?
Gerald P. Bodey Sr., MD:
After I had started doing the studies with several different drugs, the people at the company would usually be calling me saying, “We’ve got this new drug.” Sometimes it worked the other way around, where I heard they had a new drug and all. But I had an extensive relationship with a whole host of drug companies that were making new antibiotics. We were able, because of the nature of our patient population, to accumulate fairly large numbers of patients for these new drugs, so I generally didn’t have any problem getting involved with new studies. For example, with the carbenicillin, in our first study of Pseudomonas infections we had a 91% cure rate with carbenicillin. The whole death rate from Pseudomonas fell from 31% to 8% with carbenicillin, so it had a very dramatic impact on Pseudomonas infection. Now, it didn’t work against some other organisms, but it was very effective in treating Pseudomonas. So then we began looking at antibiotic combinations. We looked at carbenicillin plus gentamicin—that was one of the studies that we did. Actually, before carbenicillin became available, the only antibiotics that had any activity against Pseudomonas were colistin, polymyxin, and gentamicin, and they were basically ineffective if the patient didn’t have any neutrophils. So this really made a big improvement for our leukemic population. And having these patients that would get Pseudomonas infections, we now finally had an antibiotic we could use and treat them effectively. So it really did make a big difference.
Tacey Ann Rosolowski, PhD:
Now, during this period, in the sixties and in the seventies and into the eighties, was there unusually—was it an unusually active period of drug companies producing new antibiotics? Did it help that you were doing research? Did that stimulate interest on the part of the drug companies to develop new drugs?
Gerald P. Bodey Sr., MD:
No. I wouldn’t—I don’t think that had any role. It was just that that was an area of interest on the part of the pharmaceutical industry. And coming up with some of these new drugs and being able to do studies—some of them turned out to be very effective, and they made tons of money out of them. Some of them, unfortunately, didn’t. But most of them really did have some niche where they were beneficial.
Tacey Ann Rosolowski, PhD:
I guess I was wondering if the drug companies discovered—for example, there was that drug that was not effective with neutropenic patients. Did that suddenly clue them in to the fact that, “Oh, here’s a need. Now we’ll try to create a drug that fills that need.”
Gerald P. Bodey Sr., MD:
No, they just—I think it’s fair to say that in general they focused their attention on where their drug was effective.
Tacey Ann Rosolowski, PhD:
I see.
Gerald P. Bodey Sr., MD:
And finding a new drug isn’t exactly an easy thing to do. Sometimes it was just serendipitous. Sometimes they got them, and sometimes they had a study where they were trying to evaluate or modify an existing antibiotic and those kinds of things, although it worked sort of both ways. But over the years, we had the opportunity to study quite a few antibiotics. Some of them really made major differences, and carbenicillin was one of those. We also did a big study on looking at the relationship between the circulating neutrophil counts and infection in patients with acute leukemia. We studied 52 patients for 17,743 days, so it was a big. We looked then at the percent of these with infection related to their granulocyte count—the neutrophil count. What we found was that out of the total population where the neutrophil count was less than 100, there were 43 episodes per 1000 days. However, if it was greater than one thousand, there were five episodes per one thousand days. But it was higher if they were in relapse of their cancer than if they were in remission. So we were doing those kinds of studies in addition to cancer chemotherapy. There were several institutions around the country and around the world that had focuses on infection and cancer patients, but we were amongst the largest, and I think we did probably more studies than any other institution.
Tacey Ann Rosolowski, PhD:
What was the significance of the study that you just mentioned? Why was that paper so important in particular?
Gerald P. Bodey Sr., MD:
Because it identified what the patient’s risk was of getting an infection. Sometimes that even had some impact on the intensity of the chemotherapy. You didn’t want to give too much and have a long period of no neutrophils and the patient then getting infected.
Tacey Ann Rosolowski, PhD:
Why was MD Anderson able to do these studies in a particularly broad and well-resourced way, do you think?
Gerald P. Bodey Sr., MD:
We had a fairly large population of those patients, and it was well organized, because—particularly leukemic patients, because they were under Dr. Freireich’s department. But even with the solid tumor patients, most of the new adjuvant chemotherapy that was being done was being done in our Department of Developmental Therapeutics of which Dr. Frei and Dr. Freireich were in charge. So I think that was the major factor. Things were pretty well organized.
Tacey Ann Rosolowski, PhD:
I was curious; some people—some interview subjects—who have reflected back on this period when Developmental Therapeutics had first been established and when it was in its early years—they said that some of the studies that were being done in Developmental Therapeutics were kind of controversial. Was the work that you were doing with the infectious diseases controversial in any way?
Gerald P. Bodey Sr., MD:
No, I wouldn’t think so. I’m not sure what they meant by being controversial.
Tacey Ann Rosolowski, PhD:
Well, I think that—at least with the chemo studies—I think there were some questions about the dosage levels that were being given or the way that they felt maybe patients were being experimented on in unusual ways.
Gerald P. Bodey Sr., MD:
Sure. I mean, the people were experimented on, because if you had nothing to offer—if you knew that the only other things they had to offer weren’t going to be any good, then why not use this new drug? Yes, that was a major part of the Department of Developmental Therapeutics was developing new drugs. They made a very important contribution to the advancement of chemotherapy of cancer. And you can’t do that unless you’re starting with new drugs. You have to start somewhere. So what else were you going to do? I mean, they weren’t doing it without any background information. There had been prior in vitro studies with cells. There had been prior animal studies and that sort of thing. So it wasn’t that they just got a bowl out of the blue and started giving something to patients. They did it, and they did it in a well-organized fashion. They would have a protocol and the protocol was followed, dosages were the same for all patients in escalations and so no—not one patient getting one thing, somebody getting something else. So yes, it was investigational. A lot of things were—but you have to start somewhere. I mean, you don’t know whether a drug is going to do any good or whether it’s going to have serious toxicities until you start using it. But I think that everything was done in a very orderly fashion with protocol, not some haphazard “let’s give this guy so and so.” It was well done, and people were watching over things carefully and analyzing the data and so on. I know that there were people at MD Anderson who didn’t like the Department of Developmental Therapeutics and had some unkind things to say about them. But my own view—of course, I was part of that department—was that things were done in a very orderly fashion and with as much knowledge as was available, but you have to start somewhere. There were a lot of advances that were made as a consequence of the work that was done in cancer chemotherapy. Now, I was part of the chemotherapy as well as the infectious diseases, so obviously I have a little bit of a bias. But I can’t think of any things that were don’t that were just casual or careless or whatever. They were well thought out and followed carefully and so on. There were times when a drug was used that turned out to be toxic or something, so we stopped using it as soon as we knew that, but you aren’t ever going to know until you use it. I think that’s a little inappropriate. I’m not—now maybe they know something that I’ve forgotten, but I don’t remember any careless chemotherapy being done. Some things would be considered by more cautious people as being a little too experimental or something, but we did make some major contributions to cancer chemotherapy that are still being used today.
Tacey Ann Rosolowski, PhD:
Absolutely. I mean, I get a sense that there was almost a philosophical difference on how much risk you take.
Gerald P. Bodey Sr., MD:
Let’s see. Well, I have a lot of information about the relationship between infection and neutrophil counts and so on, but that was well established.
Tacey Ann Rosolowski, PhD:
Is there something that you’d like to share about that?
Gerald P. Bodey Sr., MD:
I’ll give you all this when I’m done. What was important was that we learned from these experiences and then we developed antibiotic regimens that were really beneficial. As I pointed out already with Pseudomonas, if you had a neutrophil count of 100 and you got a Pseudomonas bacteremia, you were going to die. I mean, chances of recovering were almost zero until carbenicillin came along, and the carbenicillin and gentamicin combination—a substantial number of those patients survived their infections. And of course, we also were using white cell transfusions. I’m sure somebody talked to you about them. I’m not going to get into that, but that was an important component as well. If you want to turn it off just a second, I may look through here.
Tacey Ann Rosolowski, PhD:
Sure, just pause this. (End of Audio 1 Session 3)
Recommended Citation
Bodey, Gerald P. MD and Rosolowski, Tacey A. PhD, "Chapter: 12 Key Studies of Infection in Leukemia Patients" (2013). Interview Chapters. 996.
https://openworks.mdanderson.org/mchv_interviewchapters/996
Conditions Governing Access
Open
