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  • Acute lymphoblastic leukemia (ALL) is classified into B-cell ALL, T-cell ALL, and natural killer cell ALL. Cytogenetics are key in the diagnosis of ALL because they hold a predictive and prognostic value. A Philadelphia chromosome–like signature that lacks the expression of BCR-ABL1 fusion protein but does have a gene expression profile similar to BCR-ABL1+ ALL has been recently defined.

  • Measurement of measurable residual disease (MRD) using multiparameter flow cytometry, quantitative polymerase chain reaction, and next-generation sequencing is standard of care in the treatment of patients with ALL, and it holds prognostic as well as predictive significance. Treatment of patients with MRD-positive disease after achievement of response consists of the use of immunotherapy, such as blinatumomab or combinatorial agents.

  • The frontline therapy of patients with ALL consists of four major components: induction of remission, consolidation, maintenance, and central nervous system prophylaxis. Intensive induction chemotherapy regimens are modeled after either the pediatric-inspired roadmap regimens or the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen. Consolidation depends on the risk category and consists of either consolidation chemotherapy (e.g., high-dose methotrexate and cytarabine) or allogeneic hematopoietic stem cell transplant. Maintenance consists of POMP (Purinethol, Oncovin, methotrexate, and prednisone) or DOMP (Dexamethasone, Purinethol, Oncovin, and methotrexate) chemotherapy for 2 to 3 years. Clinical trials are evaluating the use of novel agents, such as antibody–drug conjugates and bispecific antibodies, in the frontline setting.

  • The combination of chemoimmunotherapy is the mainstay of treatment of patients with ALL and is a field of ongoing research to identify the best combinations as well as timing of their use.

  • In adolescents and young adults, pediatric regimens and the hyper-CVAD regimen showed similar complete remission rates, remission duration, and survival outcomes.

  • The role of allogeneic hematopoietic stem cell transplantation (AHSCT) in first remission remains currently valid in certain high-risk circumstances, such as (1) KMT2A-rearranged ALL, (2) early T-cell precursor ALL, and (3) ALL with complex cytogenetics and hypodiploidy.

  • In the salvage setting, a number of novel agents have been approved, including monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell therapies.


Acute lymphoblastic leukemia (ALL) is characterized by the proliferation and accumulation of lymphoid progenitor cells in the blood, bone marrow, and other tissues. It has a bimodal distribution. The overall age-adjusted incidence is 1.7 per 100,000 persons, with a peak in early childhood and then a smaller peak in older adults. Approximately 60% of cases are diagnosed in patients who are 20 years old or younger. In 2020, the American Cancer Society estimated that 6150 individuals would be diagnosed with ALL in the United States that year, and 1520 patients would succumb to the disease.1 ALL is projected to represent 20% of adult leukemias and 46% of leukemias in teenagers (15–19 years old) and will be the most common childhood acute leukemia in children 14 years old and younger, representing approximately 75% in this patient population.1

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