Hair loss Treatment Center

GREG BERK, MD:  Hello, my name is Dr. Greg Berk from Cornell Medical Center in New York City.  And I am pleased to have Dr. Julie Vose, Professor and Vice Chairman of the Department of Internal Medicine at the University of Nebraska Medical Center.  Welcome, Dr. Vose.

Today's topic, Dr. Vose, is going to be on indolent non-Hodgkin's lymphoma, obviously a big category of disease of which there are many specific issues to discuss.  But I thought, as an introduction to this, that I would ask about where the indolent lymphomas fit into the new classification systems.
 

JULIE VOSE, MD:  The new classification system is actually going to be published this fall as the World Health Organization classification system.  And it is a revised version of the REAL system which is the Revised European-American Lymphoma classification system.  This system is based not on calling the lymphomas indolent, intermediate, or high-grade lymphomas, but rather is based on their immunophenotyping or B- and T-cell lineage.  So it doesn't really divide the types of lymphomas based on their clinical outlook but based on what they look like under the microscope.

Most of the indolent lymphomas fit into the B-cell category.  For the most part they would be included in the small lymphocytic, follicular lymphomas and then some various other subclassifications, such as marginal cell lymphoma that's a new classification in this system.  So they've pretty much been spread out, but most of them remain in the B-cell category.
 

GREG BERK, MD:  Most practicing oncologists, Dr. Vose, have viewed the treatment of indolent lymphomas as a real art in the sense that these are often the more difficult patients with which to decide who should receive treatment, who should not.  Who should you take a watchful waiting approach with?  And then when you do decide on treatment there are a whole host of options.  There really is no standard of care for this disease, is there?
 

JULIE VOSE, MD:  Unfortunately, there is not a standard of care I would say, and what I always tell patients is that if they see ten different oncologists, they're going to get ten different answers because nobody knows what the right answer is.  So I usually go over all the options with the patients, try and see what their thoughts are.  A lot of the younger patients in particular are not willing to do the watch-and-wait strategy and sometimes the older patients are.  And I think it's, as you mentioned, a little bit more of an art form as opposed to a lot of science in there.

What I would recommend, however, is for patients who either are ready for treatment based on the clinical status, or who do want to seek treatment no matter what, that they should be placed on clinical trials trying to evaluate some of our new therapies that are available for lymphomas, such as the antibodies, vaccines, or other new chemotherapy drugs because this is really the only way we're going to be able to decide what is best for these patients.

GREG BERK, MD:  Dr. Vose, are there any trials that come to mind right now that are going on in this country which you particularly view as high-priority type of trials to help answer questions about the best treatment options for these patients?
 

JULIE VOSE, MD:  Yes, I think a couple of trials for patients with newly diagnosed follicular lymphoma, in particular, are very important.  The trials that we're doing here and that I think are also important nationally would be vaccine trials that use the patients own lymphoma to make a vaccine for themselves.  And it's given to the patient after standard-dose chemotherapy to try and maintain their complete remission.  And that treatment has been going on at Stanford for many years, and at National Cancer Institute, but it's just started to be done at other locations such as here at the University of Nebraska.

And the other trials I think that are very important nationally would be some of the trials that are using combination therapies such as CHOP chemotherapy with the Rituximab antibody or CHOP chemotherapy with the radiolabeled antibody, Bexxar, and try to see if we can maintain the patient's complete remission by adding that antibody to standard treatment.  And there are several phase II trials going on and then in the future phase III trials will be performed as well.
 

GREG BERK, MD:  In most of these antibody trials that you're referring to, are the antibodies given to patients in a consolidation phase or after chemotherapy has induced a complete clinical remission?
 

JULIE VOSE, MD:  There are several different ways that the antibodies can be given.  Most of the trials that I mentioned do give the antibodies in a consolidation method that is after the patients completed their CHOP chemotherapy.  There are also some other trials that have used the antibodies, in particular the Rituximab antibody, in conjunction with or at the same time the chemotherapy is given, in effect to try and use the synergistic action that's been noted in vivo of those antibodies.  So several different ways to be able to give the antibody and they all need to be studied to see which is the best way.

GREG BERK, MD:  I know we have only one antibody currently on the market, Rituxan, but we're anticipating  another one, Bexxar, on the market soon.  And perhaps within the next few years two or three other antibodies.  How are practicing oncologists going to know which antibody to use?
 

JULIE VOSE, MD:  I don't think it's necessarily a question of which one to use, I think they're probably all going to be used perhaps in the same patient, even in subsequent time periods.  Just because you fail one antibody does not necessarily mean that you are resistant with the other one.  So I think there is a possibility that several different antibodies could be used, even perhaps in combination with each other as an option.  And so there is a lot of work we have yet to do to try and find out which is the best way and which is the best combination.
 

GREG BERK, MD:  Dr. Vose, can you comment on our current thinking of how stem cell transplantation fits in to the treatment schema in the patient with indolent non-Hodgkin's lymphoma?
 

JULIE VOSE, MD:  Hmmh...  This is a pretty controversial issue and for many years, physicians did not refer their patients for transplant for follicular or indolent lymphoma because of their long-life expectancy.  But over the past decade, I would say, this has become more of a common practice and so we now have some long-term data for those patients.  And what we can tell from most of the autologous stem cell data is that for patients who are transplanted after they have failed multiple therapies, this just does not appear to be a beneficial mode in it.  Although it may prolong the time they are without disease for a little bit, it does not look like that cures patients, if they've failed multiple prior therapies.

However, if they receive transplantation early in the course of the disease, the data at least here at the University of Nebraska would show that a large percentage of those patients can maintain long-term disease-free survival. Whether that's curative at this point, I think we still don't have long enough data to know.

Another issue is the use of allogeneic transplantation for patients with indolent lymphoma.  And many centers are turning to that as an option because autologous transplant does not appear to be curative long term for multiply relapsed patients.

There is some data from the International Bone Marrow Transplant Registry that has follow-up at least out to six or seven years that looks like the remissions can be maintained with allogeneic transplant.  But there is always the concern of increased morbidity and mortality related to that type of transplant.  So I think for young patients, that is still an option and is one that I do discuss with them when they come to see me.
 

GREG BERK, MD:  Dr. Vose, is there any information on incorporating biological therapies such as immunotherapy or even alpha-interferon or monoclonal antibody therapy after bone marrow transplantation?
 

JULIE VOSE, MD:  There have been a number of different multi-phase II trials that have been performed with a number of different agents.  There was an interferon study where patients received interferon post-transplant to try and maintain a remission.  And that was a prospective randomized trial and that actually did not show any benefit for patients that were transplanted and then given interferon.

There is an ongoing trial trying to look at interleukin-2 post-transplant.  And the prospective randomized trial is not finished for that particular agent.

There are also a number of different phase II trials looking at combining the antibody, the Rituximab or Bexxar antibody with the high-dose therapy in a transplant regimen.  A number of different ways to do that.  One would be to give the Rituximab prior to collecting the stem cells to try and do an in-vivo type purge.  And then most of the trials also give the antibody at some point post-transplant.

There are a couple of studies using the Bexxar antibody in the preparative regimen for high-dose therapy and transplant, either in very high doses, as has been used by Dr. Press, or in lower doses which is a protocol that I'm doing here.  Probably the radiation-labeled antibodies are not going to be as useful post-transplant due to the increased problems of the hematopoietic toxicity.  But pre-transplant and as part of the preparative regimen, they could be very useful.  So several studies currently ongoing are looking at that.
 

GREG BERK, MD:  I have one more question for you, Dr. Vose. Are you finding that the purine analogs to be helpful in treating patients with low-grade lymphomas?
 

JULIE VOSE, MD:  I think purine analogs are excellent drugs for patients with indolent lymphomas.  I don't, however, think they are any more beneficial than the rest of the chemotherapy agents we have.  They do work by different mechanisms so that patients who have failed other prior chemotherapy such as alkylating agents can often respond to the purine analogs.  Unfortunately, however, I don't think that it prolongs the survival of patients.
 

GREG BERK, MD:  Dr. Vose, I very much appreciate your taking the time today to discuss the indolent lymphomas.  Your comments have been very helpful.  Thank you.
 

JULIE VOSE, MD:  Thank you.