RT Book, Section A1 DeRemer, David A1 Higgins, Tara A2 DiPiro, Joseph T. A2 Yee, Gary C. A2 Posey, L. Michael A2 Haines, Stuart T. A2 Nolin, Thomas D. A2 Ellingrod, Vicki SR Print(0) ID 1182475767 T1 Acute Leukemias T2 Pharmacotherapy: A Pathophysiologic Approach, 11e YR 2020 FD 2020 PB McGraw-Hill Education PP New York, NY SN 9781260116816 LK accesspharmacy.mhmedical.com/content.aspx?aid=1182475767 RD 2024/03/28 AB KEY CONCEPTS Acute leukemias are the most common malignancies in children and the leading cause of cancer-related death in patients younger than age 20 years. Several risk factors correlate with prognosis for acute lymphoblastic leukemia (ALL). Poor prognostic factors include high–white blood cell (WBC) count at presentation, very young or very old age at diagnosis, delayed remission induction and presence of certain cytogenetic abnormalities (eg, Philadelphia chromosome positive [Ph+]). For children with ALL, remission induction therapy includes vincristine, a corticosteroid, and asparaginase, with or without an anthracycline. For adults with ALL, vincristine, prednisone, an anthracycline, and asparaginase are used. All patients with ALL require prophylactic therapy to prevent CNS disease because of the high risk of central nervous system (CNS) relapse. The choice for therapy includes a combination of the following: cranial irradiation, intrathecal chemotherapy, or high-dose systemic chemotherapy with drugs that cross the blood-brain barrier. Long-term maintenance therapy for 2 to 3 years is essential to eradicate residual leukemia cells and prolong the duration of remission. Maintenance therapy consists of oral methotrexate and mercaptopurine, with or without monthly pulses of vincristine and a corticosteroid. Disease-free survival is lower in adults with ALL and has been attributed to greater drug resistance, poor side effect tolerance with subsequent nonadherence, and possibly less effective therapy. This population is also more likely to have Ph+ ALL, which is associated with a worse outcome, but the use of tyrosine kinase inhibitors (TKIs) has improved treatment results. Several poor prognostic factors for adult acute myeloid leukemia (AML) include older age, organ impairment, presence of extramedullary disease, and presence of certain cytogenetic and molecular abnormalities. Treatment of AML usually includes therapy with an anthracycline and cytarabine. Postremission therapy is required in all patients and can include either consolidation chemotherapy with or without maintenance therapy, or hematopoietic stem cell transplantation (HSCT). Novel oral therapies that inhibit FMS-related tyrosine kinase (FLT-3), isocitrate dehydrogenase (IDH1 and IDH2), and B-cell leukemia/lymphoma (BCL-2) have emerged in the AML treatment landscape. Treatment of acute promyelocytic leukemia (APL) consists of induction therapy, followed by consolidation and maintenance therapy. Induction includes tretinoin and an anthracycline; consolidation therapy consists of two to three cycles of anthracycline-based therapy; maintenance consists of pulse doses of tretinoin, mercaptopurine, and methotrexate for 2 years. Hematopoietic growth factors can be safely and effectively used with myelosuppressive chemotherapy for acute leukemias. They reduce the incidence of serious infections, hospital length of stay, and treatment delays, but do not prolong disease-free survival or overall survival.