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This established tradition, accepted because of the high cure rates in childhood ALL, has been challenged by the development of highly active targeted therapies.<\/jats:p><\/jats:sec><jats:sec id=\"ab-crv250003-2\"><jats:title>Observation<\/jats:title><jats:p>Treatment modalities, combined with less and shorter chemotherapy durations, have produced better results than chemotherapy. The novel therapies include using the more potent <jats:italic>BCR::ABL1<\/jats:italic> tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome\u2013positive ALL and combining blinatumomab and\/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. These have been associated with improved 4-year survival rates of 85% to 90% in Philadelphia chromosome\u2013positive ALL and 80% to 85% in B-cell ALL.<\/jats:p><\/jats:sec><jats:sec id=\"ab-crv250003-3\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The management of ALL is changing rapidly. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. 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