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Pediatric-Inspired Regimens in ALL

Panelists: Mark R. Litzow, MD, The Mayo Clinic; Jae Park, MD, Memorial Sloan Kettering Cancer Center; Bijal Shah, MD H. Lee Moffitt Cancer Center & Research Institute; Anthony Stein Gehr Family Center for Leukemia Research
Published: Wednesday, Jan 30, 2019



Transcript: 

Mark R. Litzow, MD:  Taking that into account, Anthony, how do you approach treating patients with, let’s start out with Philadelphia [Ph]-negative B-cell ALL.

Anthony S. Stein, MD: When I see a patient with newly diagnosed Ph-negative ALL, I risk-stratify them by half if they are. And the age of the patients. So somebody who is fit and younger than age 50, that type of patient I would treat with an AYA [adolescent and young adult] regimen. And the data now show that using an AYA regimen, definitely up to the age of 40, and some of the AYA regimens extend up to age 50, for these patients you have a 90% complete remission rate, and around a 50% to 60% 5-year survival.

So say if somebody was treated with an AYA regimen throughout the 30s, is MRD [minimal residual disease]-negative, that type of patient may just continue on that AYA regimen and will not be transplanting in first remission unless they have high-risk cytogenetic or mutational features such as a Philly-like hypodiploidy MLL rearrangement. [Those] would be the main poor-risk cytogenetic abnormalities.

Mark R. Litzow, MD: Tell us what you mean by an AYA regimen just so we’re all clear about that.

Anthony S. Stein, MD: It’s a pediatric inspired regimen. Basically you’re using a 4-drug induction regimen; we use anthracycline, vincristine, prednisone or dexamethasone, and asparaginase. Then patients usually go through an intensification phase, an intra-maintenance phase, a delayed consolidation phase, followed by maintenance therapy.

During the intensification and consolidation phase patients are given several intrathecal therapies to prevent CNS [central nervous system] relapse. And that’s also intensified to give patients more asparaginase. It has been shown that by giving more asparaginase you increase the CR [complete response] rate and also decrease the relapsed rate over time.

Mark R. Litzow, MD: What I tell our fellows is that the pediatric regimens use a lot more of the nonmyelosuppressive drugs—asparaginase, corticosteroids, vincristine. I think that’s a big difference.

Anthony S. Stein, MD: The goal of the pediatric regimen, in AML [acute myeloid leukemia], we basically give patients ablative therapy and make them pancytopenic, and wait for their counts to recover. For ALL, the goal is to treat them, not make them as cytopenic, and extend the treatment over a more prolonged time, alternating between myelosuppressive agents and nonmyelosuppressive agents. And in the pediatric setting, they’re approaching 5-year survivals now, 90%, 90+%.


Transcript Edited for Clarity

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Transcript: 

Mark R. Litzow, MD:  Taking that into account, Anthony, how do you approach treating patients with, let’s start out with Philadelphia [Ph]-negative B-cell ALL.

Anthony S. Stein, MD: When I see a patient with newly diagnosed Ph-negative ALL, I risk-stratify them by half if they are. And the age of the patients. So somebody who is fit and younger than age 50, that type of patient I would treat with an AYA [adolescent and young adult] regimen. And the data now show that using an AYA regimen, definitely up to the age of 40, and some of the AYA regimens extend up to age 50, for these patients you have a 90% complete remission rate, and around a 50% to 60% 5-year survival.

So say if somebody was treated with an AYA regimen throughout the 30s, is MRD [minimal residual disease]-negative, that type of patient may just continue on that AYA regimen and will not be transplanting in first remission unless they have high-risk cytogenetic or mutational features such as a Philly-like hypodiploidy MLL rearrangement. [Those] would be the main poor-risk cytogenetic abnormalities.

Mark R. Litzow, MD: Tell us what you mean by an AYA regimen just so we’re all clear about that.

Anthony S. Stein, MD: It’s a pediatric inspired regimen. Basically you’re using a 4-drug induction regimen; we use anthracycline, vincristine, prednisone or dexamethasone, and asparaginase. Then patients usually go through an intensification phase, an intra-maintenance phase, a delayed consolidation phase, followed by maintenance therapy.

During the intensification and consolidation phase patients are given several intrathecal therapies to prevent CNS [central nervous system] relapse. And that’s also intensified to give patients more asparaginase. It has been shown that by giving more asparaginase you increase the CR [complete response] rate and also decrease the relapsed rate over time.

Mark R. Litzow, MD: What I tell our fellows is that the pediatric regimens use a lot more of the nonmyelosuppressive drugs—asparaginase, corticosteroids, vincristine. I think that’s a big difference.

Anthony S. Stein, MD: The goal of the pediatric regimen, in AML [acute myeloid leukemia], we basically give patients ablative therapy and make them pancytopenic, and wait for their counts to recover. For ALL, the goal is to treat them, not make them as cytopenic, and extend the treatment over a more prolonged time, alternating between myelosuppressive agents and nonmyelosuppressive agents. And in the pediatric setting, they’re approaching 5-year survivals now, 90%, 90+%.


Transcript Edited for Clarity
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