The history of treatment of chronic myeloid leukemia

Abstract

First descriptions of leukemia by Cullen, Velpeau, Donne, Craigie and Bennett were published few years before the observation by Rudolf Virchow (1845) considered as discoverer of chronic myeloid leukemia (CML). In 1878 Neumann reported that the cells responsible for leukemia originate from the bone marrow, and Ebstein in 1889 used the term “acute leukemia” to distinguish it from the chronic one. The first agent used in therapy of CML was Fowler’s solution — a 1 percent solution of arsenic trioxide. First radiotherapy was performed in 1903 and splenectomy in 1886. Modern chemotherapy started with the use of cyclophosphamide (1946) — a cyclic ester of mustard gas used as a poison gas in Ypres in 1917. In 1952 busulfan and in the 1960s hydroxyurea and leukapheresis had been introduced. Interferon alpha introduced in the 1980 was the first agent which improved the prognosis of CML. In 1978 first experimental allogeneic bone marrow transplantation has been performed, and starting from 1994 attempts were made to perform autologic transplantation. Modern therapy which radically changed the prognosis of CML started in June 1998 with the first administration of beta cristal form imatinib; a first generation tyrosine kinase inhibitor (TKI). In 2004 and 2005 clinical trials with second generation TKIs: dasatinib and nilotinib respectively had been commenced. In 2008 ponatinib — a third generation TKI was introduced into phase I clinical trial for patients with T315I mutation responsible for resistance to all yet used TKI.