TY - CHAP M1 - Book, Section TI - Chronic Leukemias A1 - Kiel, Patrick J. A1 - Grove, Meagan A2 - DiPiro, Joseph T. A2 - Yee, Gary C. A2 - Posey, L. Michael A2 - Haines, Stuart T. A2 - Nolin, Thomas D. A2 - Ellingrod, Vicki Y1 - 2020 N1 - T2 - Pharmacotherapy: A Pathophysiologic Approach, 11e AB - KEY CONCEPTS Chronic myeloid leukemia (CML) is defined by the presence of the Philadelphia chromosome (Ph), a translocation between chromosomes 9 and 22. The resulting abnormal fusion protein, p210 BCR-ABL, phosphorylates tyrosine kinase residues and is constitutively active, resulting in uncontrolled hematopoietic cell proliferation. Without treatment, the disease course of CML is characterized by a progressive increase in white blood cells over a period of years that ultimately transforms into acute leukemia. The commercially available tyrosine kinase inhibitors, imatinib, dasatinib, nilotinib, bosutinib, and ponatinib have demonstrated efficacy in the treatment of newly diagnosed CML patients and in patients with either accelerated phase or blast crisis. CML monitoring requires the assessment of milestones throughout the therapy such as hematologic, cytogenetic, and molecular responses, the ideal of which is a molecular response. Allogeneic hematopoietic stem cell transplant (HSCT) is the only known curative treatment option for CML and is reserved for patients with a suitable donor and progression after treatment with tyrosine kinase-based therapy. The management of chronic lymphocytic leukemia (CLL) is highly individualized and includes observation in patients with early-stage disease and treatment with targeted therapy, chemotherapy, biologic therapy, or both in patients with more advanced disease. Alemtuzumab, ofatumumab, obinutuzumab, and rituximab are monoclonal antibodies that are indicated for the treatment of CLL. Regimens such as fludarabine, cyclophosphamide, and rituximab are considered as first-line therapy for patients with CLL who are younger or have more aggressive disease. Novel agents such as ibrutinib, idelalisib, duvelisib, venetoclax, and acalabrutinib provide an orally administered option for the treatment of CLL. Ibrutinib is approved for treatment of previously untreated patients and for patients with relapsed disease who have received at least one prior therapy. Oral agents such as venetoclax and idelalisib in combination with monoclonal antibodies are now first-line treatment options in patients with comorbidities. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accesspharmacy.mhmedical.com/content.aspx?aid=1182476157 ER -