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Content Update

September 21, 2017

Midostaurin (Rydapt®) for FLT3-Positive Acute Myeloid Leukemia: Midostaurin is an FLT3 tyrosine kinase inhibitor that is FDA-approved for treatment of adults with newly-diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (FLT3+) in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. In a phase 3 controlled clinical trial, midostaurin improved both overall and event-free survival when added to standard induction and consolidation chemotherapy. Midostaurin therapy is generally well tolerated with a potential increased risk of severe anemia and/or rash. The NCCN guidelines include midostaurin in addition to chemotherapy as a category 2A recommendation for AML patients with a known FLT3 mutation.

KEY CONCEPTS

KEY CONCEPTS

  • Image not available. Acute leukemias are the most common malignancies in children and the leading cause of cancer-related death in patients younger than age 20 years.

  • Image not available. 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+]).

  • Image not available. For children with ALL, remission induction therapy includes vincristine, a corticosteroid, and asparaginase, with or without an anthracycline. For adults with ALL, vincristine, prednisone, and an anthracycline are given, and asparaginase is sometimes added.

  • Image not available. 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.

  • Image not available. 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.

  • Image not available. 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 has improved treatment results.

  • Image not available. There are several poor prognostic factors for adult acute myeloid leukemia (AML): older age, organ impairment, presence of extramedullary disease, and presence of certain cytogenetic and molecular abnormalities.

  • Image not available. Therapy of AML usually includes induction 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).

  • Image not available. 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.

  • Image not available. Hematopoietic growth factors can be safely and effectively used with myelosuppressive chemotherapy for acute leukemias. The benefits may include reduced incidence of ...

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