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Patrick A. Brown, Matthew Wieduwilt, Aaron Logan, Daniel J. DeAngelo, Eunice S. Wang, Amir Fathi, Ryan D. Cassaday, Mark Litzow, Anjali Advani, Patricia Aoun, Bhavana Bhatnagar, Michael W. Boyer, Teresa Bryan, Patrick W. Burke, Peter F. Coccia, Steven E. Coutre, Nitin Jain, Suzanne Kirby, Arthur Liu, Stephanie Massaro, Ryan J. Mattison, Olalekan Oluwole, Nikolaos Papadantonakis, Jae Park, Jeffrey E. Rubnitz, Geoffrey L. Uy, Kristina M. Gregory, Ndiya Ogba and Bijal Shah

Survival outcomes for older adults with acute lymphoblastic leukemia (ALL) are poor and optimal management is challenging due to higher-risk leukemia genetics, comorbidities, and lower tolerance to intensive therapy. A critical understanding of these factors guides the selection of frontline therapies and subsequent treatment strategies. In addition, there have been recent developments in minimal/measurable residual disease (MRD) testing and blinatumomab use in the context of MRD-positive disease after therapy. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines for ALL regarding upfront therapy in older adults and MRD monitoring/testing in response to ALL treatment.

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Joseph C. Alvarnas, Patrick A. Brown, Patricia Aoun, Karen Kuhn Ballen, Stefan K. Barta, Uma Borate, Michael W. Boyer, Patrick W. Burke, Ryan Cassaday, Januario E. Castro, Peter F. Coccia, Steven E. Coutre, Lloyd E. Damon, Daniel J. DeAngelo, Dan Douer, Olga Frankfurt, John P. Greer, Robert A. Johnson, Hagop M. Kantarjian, Rebecca B. Klisovic, Gary Kupfer, Mark Litzow, Arthur Liu, Arati V. Rao, Bijal Shah, Geoffrey L. Uy, Eunice S. Wang, Andrew D. Zelenetz, Kristina Gregory and Courtney Smith

Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org.

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Patrick A. Brown, Bijal Shah, Amir Fathi, Matthew Wieduwilt, Anjali Advani, Patricia Aoun, Stefan K. Barta, Michael W. Boyer, Teresa Bryan, Patrick W. Burke, Ryan Cassaday, Peter F. Coccia, Steven E. Coutre, Lloyd E. Damon, Daniel J. DeAngelo, Olga Frankfurt, John P. Greer, Hagop M. Kantarjian, Rebecca B. Klisovic, Gary Kupfer, Mark Litzow, Arthur Liu, Ryan Mattison, Jae Park, Jeffrey Rubnitz, Ayman Saad, Geoffrey L. Uy, Eunice S. Wang, Kristina M. Gregory and Ndiya Ogba

The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management.