HISTORY OF CHRONIC MYELOID LEUKEMIA IN 1800’s

This post is about the history of one of the most important diseases in hematology, earlier known as leucocythemia, now chronic myeloid leukemia (CML). 

We will see each timeline in the history of CML in 1800s

1825- Velpeau described the case of a 63-year-old woman at autopsy who was found to have an enormous spleen and liver and whose blood was `thick, like gruel, one might have asked if it were not rather laudable pus than blood'.

1839- The  French microscopist Paul Donne  and  Bennett had seen the case of a 44 year old woman who died with gross splenic enlargement and whose blood seemed to be semipurulent; under the microscope, more than half the cells appeared to be `white globules'.

1844- This case was mentioned in a textbook on microscopy by Donne.

1841- Dr.David Craigie, a physician at the Royal Infirmary saw a patient admitted for fever, increasing weakness and abdominal swelling. He was puzzled by the unusual blood consistency and the splenic tumour this patient had, but he did not explore further.

1844, November- Dr. Craigie  saw a second patient, 28 year old man with similar features, admitted under Sir Robert Christison. He was sure that the internal pathological state was similar in both the patients.

1845, October - John Hughes Bennett got interested in this case and he was permitted to do autopsy. He submitted the report on 19 March which was published in the Edinburg Medical and Surgical Journal. He titled the paper as ‘Case of hypertrophy of the spleen and liver in which death took place from suppuration of the blood’.

Dr Craigie published details of his 1841 case in the same issue of the journal.

               John Hughes Bennett and Rudolph Virchow. Picture taken from Wikipedia.org.

1845- Robert Virchow, who was a 24 year old graduate from Berlin Army Medical School, studying pathology of phlebitis, reported his first case of a fifty year old woman, with complaints of fatigue, nosebleeds and swelling of the legs and abdomen. Virchow performed autopsy four months after her death and noted a mass closely resembling pus was seen in the blood vessels, in addition to splenomegaly. His case report was published just five weeks after Bennetts.

May be if Virchow had done the autopsy a little earlier, he would have published before Bennett.  When I read about these interesting discoveries, I feel that we should publish the study or if any novel finding, at the earliest, as soon as the study is completed, even if we feel that it’s not a great study.

Those days, there were no stains to see the cells, nor any quantitave methods like Neubauer chamber or any Coulter to count the cells.  As mentioned in my previous posts on romanowsky stains, progress in hematology stains started after 1870.

Then how did they infer that white globules were increased?

It was from a gross change in the colour of blood obtained after death and also some morphological details were made from microscopy. Bennett described the ‘colourless cells’ as having nuclei and generally composed of large granules, also here and there two or three smaller granules.’ He thought them as pus cells.

Virchow, described the nuclei of the predominant cells, as having ‘various shapes’. He used the term ‘Weisses Blut’ meaning white blood, to describe the unusual appearances of his patients blood and the usual proportion of red to white cells.

1847- Virchow also suggested the name ‘leukaemie’ for the disorder but the term did not get universal approval. He had also followed up his original reports  of nine well documented cases of leukemia and observed that in four cases, there was a close relationship between the blood appearance and splenomegaly.

1850- Dr.Henry Fuller of St.Georges Hospital in London, reported a case of a child of 9 years.

1852-Bennett proposed the term ‘leucocythaemia’, which was also the title of his major review with reports of 37 cases, published as a book in Edinburg in 1852.

Gowers later wrote the name leucocythemia, proposed by Bennett is preferred to that of Virchow (leukemia).

Craigie and Bennett initially thought that the blood appearances in their respective cases  was because of an usual infective process, either in the spleen or blood. They did not consider as a primary disturbance of leucopoiesis. But, Virchow took a definite view against the pyaemic theory of leukaemia as there was no evidence of tissue suppuration. 

Drawing of the microscopic appearances of the blood from a patient with leucocythaemia, made by Hughes Bennett (1852)

1856- He published a number of studies on the nature of the disease and summarized in 1856 in a paper.

Thirty years before staining methods for blood films were introduced, Virchow proposed two main varieties of chronic leukaemia: splenic and lymphatic.

1870-Neumann suspected that the bone marrow was an important site for blood cell formation, when he noticed the autopsy appearance of marrow being ‘dirty green yellow’ from its normal red colour. He suggested that there is a ‘myelogenous leukemia’ alongwith Virchow’s splenic and lymphatic types.

1879-Paul Ehrlich’s introduced the staining of blood films, the next important advance in classifying leukemias.

Till the introduction of stains, distinctions was made mainly on the basis of pathological changes in spleen, lymph nodes and marrow.

But by staining the smears, it was clear that the splenic form of Virchow and myelogenous form of Neumann had similar blood pictures, with increased polymorphonuclear and mononuclear cells containing granules, hence the tern splenomyelogenous leukemia was used increasingly.

1882- Dr.Arthur Conan Doyle, published in a letter to Lancet, “notes on a case of leucoythemia’. He described the case of a 29 year old man with splenomegaly with increased number if leucocytes. He assumed that this could be related to a previous attack of malaria. 

 In the next post, we shall see what happened in 1900s in the progress of CML.

 

References :

1.     The story of chronic myeloid leukaemia. British Journal of Haematology.2000:110; 2- 11

 

 

                                                                         Written by Dr.Priyavadhana B