DR. SCHIFFER: There was another adult study in CALGB that also had a 50 percent cure rate. I think that number is pretty consistent.

What is not consistent, however, is the definition of the disease that is being treated. If you look at all the adult studies and look at sort of the criteria for Burkitts, it was actually pretty unusual that they found a patient who satisfied all three, morphology, surface markers, etc.

That is suggesting that the disease, at least as it is being reported in adult series, is heterogeneous and probably consists of a couple of different disorders, at least. Is the pediatric disease much more homogeneous?

DR. CAIRO: That is actually a good question. We just now have new data to suggest that it is not. I didn't show the data because I don't have the breakout for the B ALL patients, for all the Burkitt's patients, while they all had ischemic rearrangements, 70 percent of them had other cytogenetic abnormalities.

In a multivariate analysis, some of these cytogenetic abnormalities actually predicted for prognosis.

The most common was a 1q+, but there was deletion of 17p, abnormalities at 7q and abnormalities at 3q, were the next three most common. It is also a heterogeneous group, and we are just now beginning to look at it. In our new study, we are also going to be looking at it by gene expression profiling and FISH and comparative genomic hybridization.

So, we are going to try to begin to sort it out, but I think before this, we weren't quite clear whether it was homogeneous or not.

DR. GOLDSTONE: Just for clarification, the group now potentially getting Rituximab, did they include the children with the very good prognosis?

DR. CAIRO: No, I didn't show that data, but the patients with limited stage disease that just get three weeks of therapy have a 99 percent overall survival rate. They are not getting Rituximab.

DR. GOLDSTONE: So, what is the best group in terms of conventional treatment that are now getting additional Rituximab?

DR. CAIRO: So, the best group in the new pilot is going to be what we call the intermediate risk group disease. That would be those that aren't limited stage and those that don't have B ALL CNS disease.

DR. GOLDSTONE: What are they getting on conventional therapy, in terms of outcomes?

DR. CAIRO: In terms of outcome patients with stage III and stage II disease, with this type of regimen but with the methotrexate at three grams per meter squared, their overall survival is 95 percent.

DR. GOLDSTONE: And they are getting potentially exposed to Rituximab as well?

DR. CAIRO: In the new pilot, with the idea that we will be reducing the amount of chemotherapy in the randomized study.

What I didn't show you is that the toxicity is pretty heavy. In the B ALL patients, the median days of hospitalization in the COPIT M and the CIVE courses are about 14 to 15 days, and the incidence of grade III and IV stomatitis is about 70 percent.

DR. GOLDSTONE: I was just getting worried that people with an outcome of already greater than 90 percent were going to have Rituximab thrown at them.

DR. CAIRO: The question in the subsequent study is whether we can reduce the amount of chemotherapy in that group of patients by using chemo immunotherapy. That would be the question.

DR. CARROLL: This relates to the first question about the differences between adults and children. You show a schema here with an outstanding outcome, albeit on a very aggressive chemotherapy protocol that a lot of us had to learn to use early on.

Have you considered taking some of this type of treatment and moving it up to some young adults?

DR. CAIRO: Yes, actually, thanks for bringing that up, Bill. The protocol that we have is open for young adults.

Since, in three out of the four studies, the median age was 25 to 30 years, NCI has approved this study for patients up to 30 years of age.

So, when it opens up, the hope will be that both the pediatric and the adult leukemia people will be able to enter patients on this study at their same institution.

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