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Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates in a single B- or T-lymphocyte progenitor. Proliferation and accumulation of 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 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 cases with Philadelphia chromosome and BCR-ABL1 fusion benefit from intensive treatment that includes tyrosine kinase inhibitor and transplantation of allogeneic hematopoietic stem cells in adults. 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 to 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. 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

Acronyms and abbreviations that appear in this chapter include: ALL, acute lymphoblastic leukemia; ATM, ataxia-telangiectasia mutated gene; CD, cluster of differentiation; CNAs, copy number abnormalities; CNS, central nervous system; CSF, cerebrospinal fluid; EFS, event-free survival; HLA, human leukocyte antigen; Ig, immunoglobulin; RB, retinoblastoma protein; RT-PCR, reverse transcriptase polymerase chain reaction; SEER, Surveillance, Epidemiology, and End Results.

Acute lymphoblastic leukemia (ALL) is a neoplastic disease that results from multistep somatic mutations in a single lymphoid progenitor cell at one of several discrete stages of development. The immunophenotype of leukemic cells at diagnosis reflects the level of differentiation achieved by the dominant clone. The clonal origin of ALL has been established by cytogenetic analysis, by analysis of restriction fragments in female patients who are heterozygous for polymorphic X chromosome-linked genes, and by analysis of rearrangements of T-cell receptor or immunoglobulin genes.1 Leukemic cells divide more slowly and require more time to synthesize DNA than do normal hematopoietic counterparts.2 However, leukemic cells accumulate relentlessly because of their altered response to growth and death signals.3,4 They compete successfully with normal hematopoietic cells, resulting in anemia, thrombocytopenia, and neutropenia. At diagnosis, leukemic cells not only have replaced normal marrow cells but also have disseminated to various extramedullary sites.

Velpeau5 is generally credited with the earliest report of leukemia in 1827. Virchow,6 Bennett,7 and Craigie8 recognized the condition as a distinct entity ...

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