Title: Arsenic trioxide for treating acute promyelocytic leukaemia [ID446]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of arsenic trioxide within its marketing authorisation for the treatment of acute promyelocytic leukaemia.

Lay abstract: Acute promyelocytic leukaemia is a subcategory of acute myeloid leukaemia. In both acute myeloid leukaemia and acute promyelocytic leukaemia, the production of blood cells in the bone marrow results in the development of abnormal cells. In acute promyelocytic leukaemia, the abnormal cells are white blood cells of the neutrophil type and are known as promyelocytes. These cells do not mature properly leading to a reduction of normal white blood cells in circulation. The accumulation of immature cells in the bone marrow also prevents the production of normal red blood cells and platelets resulting in anaemia, low platelet counts, pale skin or fatigue.(1) The mutation that causes acute promyelocytic leukaemia involves two genes, the promyelocytic leukaemia (PML) gene on chromosome 15 and the RARA gene on chromosome 17. A swap of genes (translocation) between chromosomes 15 and 17, fuses part of the PML gene with part of the RARA gene. The protein produced from this fused gene is known as PML-RARa, this type of genetic change is not inherited. The PML-RARA gene fusion accounts for up to 98% of cases of acute promyelocytic leukaemia.(1) There were 2,590 diagnoses of acute myeloid leukaemia and 2,127 deaths in England in 2014.(2) Around 10% of acute myeloid leukaemia cases are acute promyelocytic leukaemia.(3) The average age at diagnosis of acute promyelocytic leukaemia is 40 years compared with 65 years for acute myeloid leukaemia, 80% of people with acute promyelocytic leukaemia are aged between 15 and 55 years. Acute promyelocytic leukaemia can affect younger people but it is less common in people under 10 years of age. First-line treatment for most people with acute promyelocytic leukaemia involves treatment with the AIDA regimen which involves the use of tretinoin (also known as all-trans-retinoic acid or ATRA) in combination with idarubicin, an anthracycline-based chemotherapy. Treatment with ATRA can induce a complete remission in most people with acute promyelocytic leukaemia. ATRA is used in combination with an anthracycline-based chemotherapy to extend the period of remission. Following induction treatment patients usually have a period of consolidation therapy to further extend the period of remission. Second-line treatment options for people who have relapsed or refractory acute promyelocytic leukaemia include: Arsenic trioxide (ATO) in combination with ATRA, ATRA, cytarabine and hematopoietic stem cell transplantation (HSCT).(4) Stem cell transplants using a person’s own cells (ASCT) or matched donor cells (AlloSTC) can be offered, for people with relapsed or refractory disease who are young and otherwise fit.(5) For people treated with ATO in the second-line setting, consolation with an ASCT or AlloSCT is often considered. References 1 Acute promyeloctyic leukemia, U.S National Library of Medicine, https://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia. Accessed June 2017 2 Cancer Research UK, 2014, Acute myeloid leukaemia (AML) incidence statistics. Accessed June 2017 3 Genetics Home Reference, 2016, Acute promyelocytic leukemia. Accessed June 2017 4 ASH Education Book, 2006, Treatment of Acute Promyelocytic Leukemia. Accessed June 2017 5 Leukaemia Care, 2016, Acute Promyelocytic Leukaemia (APL). Accessed June 2017

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS