Systematic review of pre-clinical chronic myeloid leukaemia
Studies of a provisional entity pre-clinical chronic myeloid leukaemia (CML), which precedes chronic phase (CP) without leucocytosis or blood/marrow feature of CML CP, has been increasing.
To perform a systematic review of pre-clinical CML and analysis the data relevant to disease progression to CML CP.
We performed a literature search on 16 July 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data and evaluated the quality of studies using an 8-item tool, independently. The outcomes were percentage of Philadelphia chromosome in the number of metaphases examined (Ph%), correlation between Ph% and blood count and time progress to CML.
Our initial search returned 4770 studies. A total of 10 studies with a total 17 subjects were included. The lowest Ph%, which eventually progresses to CML, was 10%. Absolute basophil count seemed to correlate better with Ph% compared to total white cell and absolute eosinophil count. The time from the first documented pre-clinical CML to CML ranged from 12 to 48 months. The overall quality of the included studies was average.
This is the first systematic review on pre-clinical CML. This entity requires additional large-scale studies.
KeywordsChronic myeloid leukaemia Pre-clinical Asymptomatic Smoldering
We would like to thank Mr Sho Kubota for translating articles  in Japanese and Centre For Academic Information Services, Universiti Malaysia Sarawak for retrieving full text of the articles.
KJW initiated and planned the review, designed search term, screened title/abstract/article, searched full texts, performed data extraction and quality assessment, performed data analysis and interpretation, wrote the review. AST searched electronic databases, designed method of quality assessment, provided statistical consultation, wrote (main author) the sections involving quality assessment, reviewed manuscript. LCF screened title/abstract/article, performed data extraction and quality assessment, reviewed manuscript. MO supervised the work, reviewed manuscript. GS supervised the work, confirming data of article in Japanese , reviewed manuscript.
This study was funded by JSPS RONPAKU (Dissertation PhD) Program FY2017, UNIMAS Special Grant Scheme No: F05/SpGS/1401/16/2 & Fundamental Research Grant Scheme No: FRGS/SKK01(01)/1290/2015(7).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Nakagawa M, Noto S, Kobayashi H, Hayashi M. A case of a 47-year-old man who developed chronic myelogenous leukemia after therapy for multiple myeloma. J Obihiro Kosei Gen Hospital. 2003;6:101–6.Google Scholar
- 2.Wakayama T, Fujita S, Ago H. An elder patient coexisted with multiple myeloma and chronic myeloid leukemia before treatments. Med J Shimane Prefect Cent Hosp. 2005;29:63–7.Google Scholar
- 3.Vardiman JW, Melo JV, Baccarani M, Thiele J. Chronic myeloid leukemia, BCR-ABL1-positive. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri AS. WHO classification of tumors of hematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017, p. 32–7.Google Scholar
- 5.Kuan JW, Melaine Michael S. The epidemiology of chronic myeloid leukaemia in southern Sarawak, Borneo Island. Med J Malays. 2018;73(2):78–85.Google Scholar
- 6.Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497.Google Scholar
- 7.Bates I, Lewis SM. Reference ranges and normal values. In: Bain BJ, Bates I, Laffan MA, Lewis SM, eds. Dacie and Lewis practical haematology. 11 ed: Elsevier, Amsterdam 2011.Google Scholar
- 18.Van Den Berghe H, Louwagie A, Broeckaert-Van Orshoven A, David G, Verwilghen R, Michaux JL, et al. Philadelphia chromosome in human multiple myeloma. J Natl Cancer Inst. 1979;63(1):11–6.Google Scholar