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Approaching the Management of Philadelphia-Negative ALL

Insights From: Max S. Topp, MD, University Hospital of Wuerzburg
Published: Wednesday, Jan 23, 2019



Transcript: 

Max S. Topp, MD: ALL [acute lymphoblastic leukemia] is a disease that predominantly affects children. So half the patients are 18 years and older, all the way up to 85, 90. So the biggest difference in how we approach ALL is the age. And age has a huge impact also on the genetics of the disease. We find some genetic aberrations more frequently in the younger patients, and we find more adverse genetics in older patients.

So with that said, it really sets the pace for how we treat the patients. And obviously a younger patient, particularly the children, can be treated very aggressively. We have a lot of chemotherapy. They have just much better organ function. Then once you reach an age group that is beyond the age of 55, it clearly makes a big difference, such that you have to reduce chemotherapy. And once you reach the age group of 75, chemotherapy is quite often not a real option. So the cure rates in these patients really correspond to that. Whereas in the pediatric setting with today’s protocols, more than 90% of patients are cured. When we use these more pediatric-inspired protocols for the middle group, somewhere between 18 and 55 years old, cure rates drop with every decade of age. And then once we get into the age group of about 65-plus, only about 20% of the patients might be cured despite all the new modalities that we have.

As an introduction, I am an adult hematologist, so my experience really is in the age range of 18 until 85, 90. Within that age group, age is the most important consideration. But apart from age, we have risk stratifications based on categorizing patients into standard risk, high risk, and very high risk. So standard risk is everyone who doesn’t display any risk factors. There’s the second group of patients who have high risk, which means they have some cytogenetics that make them high risk, like the 4;11 translocation or hyperleukocytosis. And you would be boxing them into the high-risk group. And the very high-risk group are the Philadelphia-positive patients.

Nowadays, you get more information. We have a Ph [Philadelphia chromosome]–like signature, which also has been shown in many cooperative groups as having a very advanced prognostic situation. So with younger patients—and young in this group means for me 18 to 55—we treat them with pediatric-inspired protocols. So it is a very intense protocol using very much normal elements from pediatric-based protocols, and we try to get this therapy into the patients in this age group. Obviously, as patients mature, they also do have more comorbidities like, for example, liver function that might be impaired by previous other diseases. And that makes a difference in which substances you have to use or can’t use in that situation.

So the other thing that we also do is, based on the surface expression of certain antigens like CD20, we would add monoclonal antibodies. And that has been shown by many study groups to be a very good approach to increasing the overall survival for those patients. So it is absolutely essential to get all this information very quickly, within days, to make decisions on how you’re going to treat the patient. If they are, for example, Philadelphia chromosome–positive, you would use very different induction regimens nowadays than the ones we use in the Ph-negative setting. So after preface of 5 or 6 days, you would just straightaway jump in the first induction. And there we can really take a very different treatment approach for those patients.

Cytoreduction is a very important question. Cytoreduction is done first for the age groups. So with anyone beyond the age of 55, you would nowadays not expose them to the same strength of therapy than someone who is 18 to 55 years old. And then there are comorbidities that would obviously also be important signs to reduce the therapy. And then in someone who is Ph-positive, we clearly also use cytoreduction because there are data that show reaching the first goal of getting a patient to remission is as good using intensified chemotherapy as using just imatinib plus vincristine and dexamethasone. So that is a very important key factor of making that decision when to cytoreduce.

Transcript Edited for Clarity

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Transcript: 

Max S. Topp, MD: ALL [acute lymphoblastic leukemia] is a disease that predominantly affects children. So half the patients are 18 years and older, all the way up to 85, 90. So the biggest difference in how we approach ALL is the age. And age has a huge impact also on the genetics of the disease. We find some genetic aberrations more frequently in the younger patients, and we find more adverse genetics in older patients.

So with that said, it really sets the pace for how we treat the patients. And obviously a younger patient, particularly the children, can be treated very aggressively. We have a lot of chemotherapy. They have just much better organ function. Then once you reach an age group that is beyond the age of 55, it clearly makes a big difference, such that you have to reduce chemotherapy. And once you reach the age group of 75, chemotherapy is quite often not a real option. So the cure rates in these patients really correspond to that. Whereas in the pediatric setting with today’s protocols, more than 90% of patients are cured. When we use these more pediatric-inspired protocols for the middle group, somewhere between 18 and 55 years old, cure rates drop with every decade of age. And then once we get into the age group of about 65-plus, only about 20% of the patients might be cured despite all the new modalities that we have.

As an introduction, I am an adult hematologist, so my experience really is in the age range of 18 until 85, 90. Within that age group, age is the most important consideration. But apart from age, we have risk stratifications based on categorizing patients into standard risk, high risk, and very high risk. So standard risk is everyone who doesn’t display any risk factors. There’s the second group of patients who have high risk, which means they have some cytogenetics that make them high risk, like the 4;11 translocation or hyperleukocytosis. And you would be boxing them into the high-risk group. And the very high-risk group are the Philadelphia-positive patients.

Nowadays, you get more information. We have a Ph [Philadelphia chromosome]–like signature, which also has been shown in many cooperative groups as having a very advanced prognostic situation. So with younger patients—and young in this group means for me 18 to 55—we treat them with pediatric-inspired protocols. So it is a very intense protocol using very much normal elements from pediatric-based protocols, and we try to get this therapy into the patients in this age group. Obviously, as patients mature, they also do have more comorbidities like, for example, liver function that might be impaired by previous other diseases. And that makes a difference in which substances you have to use or can’t use in that situation.

So the other thing that we also do is, based on the surface expression of certain antigens like CD20, we would add monoclonal antibodies. And that has been shown by many study groups to be a very good approach to increasing the overall survival for those patients. So it is absolutely essential to get all this information very quickly, within days, to make decisions on how you’re going to treat the patient. If they are, for example, Philadelphia chromosome–positive, you would use very different induction regimens nowadays than the ones we use in the Ph-negative setting. So after preface of 5 or 6 days, you would just straightaway jump in the first induction. And there we can really take a very different treatment approach for those patients.

Cytoreduction is a very important question. Cytoreduction is done first for the age groups. So with anyone beyond the age of 55, you would nowadays not expose them to the same strength of therapy than someone who is 18 to 55 years old. And then there are comorbidities that would obviously also be important signs to reduce the therapy. And then in someone who is Ph-positive, we clearly also use cytoreduction because there are data that show reaching the first goal of getting a patient to remission is as good using intensified chemotherapy as using just imatinib plus vincristine and dexamethasone. So that is a very important key factor of making that decision when to cytoreduce.

Transcript Edited for Clarity
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