Chapter 91: Acute Lymphoblastic Leukemia

SUMMARY

Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates in a single B- or T-lymphocyte progenitor. Proliferation and accumulation of clonal blast cells in the marrow result in suppression of hematopoiesis and, thereafter, anemia, thrombocytopenia, and neutropenia. Lymphoblasts can accumulate in various extramedullary sites, especially the meninges, gonads, thymus, liver, spleen, and lymph nodes. The disease is most common in children but can be seen in individuals of any age. ALL has many subtypes and can be classified by immunologic, cytogenetic, and molecular genetic methods. These methods can identify clinically important, biologic subtypes, requiring treatment approaches that differ in their use of specific drugs or drug combinations, dosages of drug, or duration of treatment required to achieve optimal results. For example, cases of childhood ALL having a hyperdiploid karyotype respond well to extended treatment with methotrexate and mercaptopurine, whereas adults whose leukemic cells contain the Philadelphia chromosome and BCR-ABL1 fusion benefit from intensive treatment that includes a tyrosine kinase inhibitor and transplantation of allogeneic hematopoietic stem cells. The relative lack of therapeutic success in adult ALL is partly related to a high frequency of cases having unfavorable genetic abnormalities and partly related to poor tolerance for intensive treatment. Nearly 90 percent of children and 40 percent of adults can expect long-term, leukemia-free survival—and probable cure—with contemporary treatment. Novel immunotherapeutic approaches are under development. Currently, emphasis is placed not only on improving the cure rate but also on improving quality of life by preventing acute and late treatment-related complications, such as second malignancies, cardiotoxicity, and endocrinopathy.

Acronyms and Abbreviations

ALL, acute lymphoblastic leukemia; ARID5B, AT-rich interactive domain 5b; ATM, ataxia-telangiectasia mutated gene; CD, cluster of differentiation; CNAs, copy number abnormalities; CSF, cerebrospinal fluid; EFS, event-free survival; FISH, fluorescence in situ hybridization; HLA, human leukocyte antigen; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; RT-PCR, reverse transcriptase polymerase chain reaction; SEER, Surveillance, Epidemiology, and End Results; SNP, single nucleotide polymorphism.