Chapter 1: Acute Lymphoblastic Leukemia

KEY CONCEPTS

• 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.