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Precision medicine treatment in child leukemia. Diagnosing Minimal Residual Disease. MRD. 4
Personalized medicine or precision medicine? Top pediatric hematologist oncologist explains the difference in cutting-edge leukemia treatment. How to maximize leukemia treatment efficiency and minimize toxicity and side-effects? We live in precision medicine era of cancer treatment. Dr. Anton Titov, MD. You co-authored several important reviews in precision medicine treatment of pediatric leukemia. It is also called personalized medicine therapy for child leukemia. Dr. Anton Titov, MD. Could you please tell us what is new in precision medicine treatment of pediatric leukemia? Dr. Shai Izraeli, MD. Precision medicine targeted cancer therapy is already happening now. Perhaps we can expect leukemia cure in the next 5-10 years? Precision medicine is very important. First of all, thank you for using the term “precision medicine”. Because the most common term that is being used is “personalized medicine”. Dr. Shai Izraeli, MD. I don’t like this term so much. Every treatment is personalized! Exactly! I don’t like “personalized medicine” term so much. Because I think that from the time of Hippocrates, you know, I’m a Jewish, so from the time of the Rambam. Rambam was a doctor. He was one of the big Jewish scholars in Egypt many years ago. Treatment in medicine was always personalized. It is always personalized. But now pediatric leukemia cancer therapy is more precise. In a child leukemia there are two aspects to precision medicine. One aspect that is already in use. This is very important! We have now the technological genomic tools to identify and quantify the residual cancer cells. Dr. Shai Izraeli, MD. Let me explain it. When leukemia is diagnosed, it’s not a big deal. Everybody can diagnose leukemia. You have 100,000 cells, you look at the microscope. You see many leukemic cells. But then we treat leukemia with chemotherapy. After treatment we don’t see the leukemic cells in the microscope anymore. But we know they exist. Dr. Anton Titov, MD. How do we know leukemic cells exist? Because after a month of child leukemia cancer therapy we can stop therapy. Then leukemia will return in every child with leukemia. Cancer will return in every adult with leukemia. We need long-term therapy. We have now very precise tools. They can identify now one leukemic cell out of 10,000 normal cells. Next year we will be able to find just one cancer cell over million normal cells. We will use technologies that are called next generation sequencing. Dr. Anton Titov, MD. Why is this important? Dr. Shai Izraeli, MD. It’s important because we learned that we can adjust leukemia therapy to this measurable few cancer cells that remain. It is called minimal residual disease. These are leukemia cancer cells that remain after cancer therapy. We measure the amount of these residual leukemic disease after one month. We may discover that we don’t find the leukemia cells at all. Our diagnostic tests have a sensitivity of one to ten thousand cells, one to 100,000 or one to 1 million cells. But this doesn’t mean that there are no residual leukemic cells somewhere in the body. It means that the patient responded fantastically to leukemia therapy. We can now give less chemotherapy. Why is it important to give less chemotherapy? Because of toxicity, of course. Less cancer therapy is less dangerous. On the other hand, in the same patient we may discover that there are residual cancer cells after leukemia therapy. It could be one leukemia cell out of 1,000 normal cells. The are no cancer cells under the microscope. But by these genomic sequencing methods, we know that we need to give more leukemia therapy to a child with leukemia. After additional 2 or 3 months of leukemia therapy we may still discover that one of every 1,000 cells still is a leukemic cell. Then we need to go on to bone marrow transplant. This is a very toxic therapy. this is one way of precision medicine. We can adjust cancer therapy to the residual leukemic cells. Dr. Shai Izraeli, MD. We can identify remaining leukemic cells by the genomic Next Generation Sequencing methods [NGS]. Second type of precision medicine is developing cancer medications that precisely target the abnormal changes. Targeted leukemia treatment medications target abnormal genomic change in the leukemic cell. A fantastic example is chromosomal abnormality that is called BCR ABL. It was discovered many years ago. I don’t know why BCR-ABL discovery did not get the Nobel Prize. One of the discoverers of the BCR-ABL molecular abnormality was Professor Eli Canaani. He works at Weitzmann Institute, here in Israel. A specific leukemia cancer medication was developed. It is called imatinib (Gleevec). Imatinib was first developed for another type of leukemia. It was chronic myeloid leukemia. But we knew that acute lymphoblastic leukemia with BCR-ABL abnormality is lethal. We had to do bone marrow transplant in every child with acute lymphoblastic leukemia. But now we have targeted cancer therapy. It is imatinib (Gleevec) or with other cancer medications combined with chemotherapy. Now we can cure about 60% of children with acute lymphoblastic leukemia (ALL). Dr. Shai Izraeli, MD. We do no need to do a bone marrow transplant. we don’t need bone marrow transplant anymore for many of them. 60% is not a lot. Dr. Anton Titov, MD. We need to improve leukemia therapy further. But that’s an example of targeted cancer therapy. I just gave you the example of leukemia in children with Down syndrome. A common type of leukemia in children with Down syndrome is this. It is a Philadelphia-like chromosome leukemia. This Philadelphia-like leukemias have abnormalities that may be targeted with specific cancer medications. I think we are just in the beginning of precision medicine age for child leukemia cure.
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