Chronic myeloid leukemia—Past, present, and future

Abstract

THESTORYOF chronicmyeloid leukemia (CML) has fascinated clinicians and hematologists for many years—though perhaps more in the 20th than in the 19th century—and possibly the story will become even more fascinating from now on. CML was arguably the first type of leukemia to be recognized, almost simultaneously in Scotland and in Germany. In 1841 David Craigie in Glasgow saw a patient with fever, splenomegaly, and leukocytosis; he saw a second similar patient 3 years later6 and this led his colleague John Hughes Bennett, a physician and pathologist, to perform an autopsy and to describe his findings in the Edinburgh Medical and Surgical Journal in 1845.3 More or less simultaneously, Rudolph Virchow, a brilliant young medical graduate in Berlin who later gained a reputation for uncompromisingly radical political attitudes, saw a similar patient at the Berlin Charite Hospital. She died 4 months later and Virchow noted at autopsy enlargement of the spleen and “everywhere in the blood vessels a mass closely resembling pus was found.”18 His report was published in Frorieps Notizen a few weeks after Bennett’s paper. In the absence of telephones or e-mail, it is unlikely that Virchow learned of Bennett’s publication (or vice versa) until somewhat later. The sequence of events is recounted in some detail in an excellent recent review by Geary.10 Although cases that we would today call leukemia had been described previously, it is probably fair to attribute to Bennett and Virchow the first full descriptions. There was, however, a difference of interpretation. Bennett concluded that his patient had died from “the presence of purulent matter in the blood,” implying some occult infection as the cause. Virchow was less inclined to attribute the excess of colorless corpuscles to “pyemia” and coined the descriptive term “Weisses Blut” or “white blood”; this was based on the Greek ( s and i ) and became in German “Leukamie.” Bennett meanwhile produced the term “leucocythaemia” or “white cell blood.”4 The claim of priority between the two authors was debated subsequently and arguments over correct nomenclature continued acrimoniously for some years. The conflict is well summarized by Gunz11 but with hindsight one may speculate that perhaps Virchow was a fraction nearer to the truth. By 2003 the definition of the nosological entity “chronic myeloid leukaemia” has achieved a fair level of consensus, even if the precise spelling (leukemia or leukaemia) and nomenclature (myeloid, myelogenous, or myelogenic) vary a little and acceleratedphase disease still defies a universally agreed definition. The recently published World Health Organization classification of tumors defines CML as “a myeloproliferative disease that originates in an abnormal pluripotential bone marrow stem cell and is consistently associated with a Philadelphia (Ph) chromosome and/or the BCR/ABL fusion gene.”17 This seems reasonable but no doubt there will be further attempts to define and classify CML and its various phases as the present century proceeds. Management of leukemia in the 19th century was no success story.8 Lissauer is credited with the first published report of the use of arsenicals,13 although full details of his work are lacking. It is interesting to note that Arthur Conan Doyle, more famous for doc-