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PRACTICE: Carolyn S Grove, George A Follows, and Wendy N Erber Incidental finding of lymphocytosis in an asymptomatic patient BMJ 2009; 338: b2119 [Full text]

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Incidental lymphocytosis

Terry J Hamblin   (4 July 2009)

Re: Incidental lymphocytosis

Edward Fitzsimons, Heather Wotherspoon   (6 July 2009)

Authors' Response to Dr Hamblin

Wendy N Erber, George A Follows, Carolyn S Grove   (9 July 2009)

Incidental lymphocytosis is not always incidental

Luke D Williamson, Lyn Williamson, Sarah Green   (30 July 2009)

Incidental lymphocytosis 4 July 2009
Terry J Hamblin, Honorary Consultant Haematologist Royal Bournemouth Hospital, BH7 7DW Send response to journal: Re: Incidental lymphocytosis	The Practice Point of Grove et al is a little out of date. The diagnosis of CLL now requires a B-lymphocyte count of 5 x 10(superscript 9)/L. [1] rather than a total lymphocyte count of 5 x 10 (superscript 9)/L as with the 1996 guidelines [2]. It is likely that a total lymphocyte count of only 8 x 10 (superscript 9)/L would not meet this threshold [3] and consequently this patient would more likely have monoclonal B lymphocytosis (MBL). The distinction may not matter in fact, but is a matter of intense investigation and one would have thought that a well known teaching hospital like Cambridge would be addressing it. It has been our practice in Bournemouth to study such cases quite intensively as a means of determining why as many as 12% of the population over 40 have MBL [4] but only about 4 per 100,000 develop CLL. References 1. Hallek M, Cheson BD, Catovsky D et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446-56 2. Cheson BD, Bennett JM, Grever M et al. National Cancer Institute- sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-7. 3. Shanafelt TD, Kay NE, Jenkins G et al. B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome. Blood 2009; 113:4188-96. 4. Nieto WG, Almeida J, Romero A et al. Increased frequency (12%) of circulating CLL-like B-cell clones in healthy individuals using a high- sensitive multicolor flow cytometry approach. Blood 2009. Prepublished online May 6, 2009;doi:10.1182/blood-2009-01-197368 Accessed July 3rd 2009. Competing interests: None declared
Re: Incidental lymphocytosis 6 July 2009
Edward Fitzsimons, Consultant Haematologist Western Infirmary, Glasgow, G11 6NT, Heather Wotherspoon Send response to journal: Re: Re: Incidental lymphocytosis	The article on Rational Testing by Grove et al, provides appropriate advice to GPs on how to manage and refer asymptomatic patients with an incidental lymphocytosis and ultimate diagnosis of chronic lymphatic leukaemia(1). The authors recommend repeat blood counts at 2-4 weeks and 3 months, with referral to Haematology clinic thereafter. This advice on rational testing does not appear to sit comfortably against a less rational cancer waiting times target that patients with a suspicion of cancer should be seen within 15 days (2). The suspicion of cancer in this case was extremely high from the outset but did not warrant urgent referral. Asymptomatic patients with monoclonal gammopathy are a similar example. These examples then highlight ongoing clinical concerns with all inclusive cancer targets. The lead cancer clinicians for the West of Scotland have expressed their concerns that cancer targets come at both a clinical cost and at the expense of audit of treatment and outcome(3). Yet clinical audit underpins cancer networks and is the key to service improvement. Now is the time to refocus cancer delivery on the results of clinical audit rather than the ever increasing demands of cancer targets. 1.Grove CS, Follows GA, Erber WN.Incidental finding of lymphocytosis in an asymptomatic patient. BMJ 2009;338:b2119 2.Waiting times for cancer 2006. www.dh.gov.uk/publications 3.Editorial;Cancer waiting times: the clinical perspective. Scot Med J 2008;53:2-4 Competing interests: None declared
Authors' Response to Dr Hamblin 9 July 2009
Wendy N Erber, Consultant Haematologist Addenbrooke's Hospital, Cambridge CB2 0QQ, George A Follows, Carolyn S Grove Send response to journal: Re: Authors' Response to Dr Hamblin	We are grateful for the comments by Dr Hamblin that highlight the current debate regarding the distinction between monoclonal B- lymphocytosis (MBL) and chronic lymphocytic leukaemia (CLL). Dr Hamblin will be aware that the proposed changes to the definition of what constitutes CLL are not uniformly accepted, and significant concerns about this issue continue to be raised in the haematology literature (Blood 2009;113:6495-6498). Under editorial guidance, the article was tailored to be a practical working document written for our colleagues working primary care, not haematology specialists. As such, all references to the distinction between MBL and CLL were beyond the remit of the article and therefore removed from the original text. We would like to reassure Dr Hamblin that in this 'well-known teaching hospital' we are following this debate with interest. Competing interests: None declared
Incidental lymphocytosis is not always incidental 30 July 2009
Luke D Williamson, Medical Student Rheumatology & Haematology Departments, Great Western Hospital NHS Foundation Trust, Swindon SN3 6BB, Lyn Williamson, Sarah Green Send response to journal: Re: Incidental lymphocytosis is not always incidental	In contrast to Grove et al., we present a case where a difficult clinical problem resolved after the empirical treatment of an apparently incidental lymphocytosis. A 68 year old woman presented with painful dactylitis and general malaise. She had a past history of spinal osteoarthritis. On examination the only significant abnormality dactylitis of both second toes. Investigations showed a lymphocytosis (5.2 to 7.7) with white cell count ranging between 13.5 and 17.1. Her haemoglobin was 101 g/L; platelets 856 x 109/L; C- reactive protein 150, and ESR 80. Extensive screening for occult malignancy, connective tissue disease and infection were negative. Initially the mild peripheral blood lymphocytosis was not felt to be relevant to the patient’s symptoms. Peripheral blood leukocyte immuno- phenotyping revealed a neoplastic B-cell clone (13% total nucleated cells; CD19, CD 20, CD23, CD5 positive and CD10 negative) consistent with a diagnosis of chronic lymphocyte leukaemia (CLL) stage A (0). Treatment with analgesics, including opiates, and combination methotrexate, sulphasalzine and leflunamide was ineffective at controlling pain or dactylitis. She was therefore treated with six, 4-weekly cycles of chlorambucil for the CLL. As the lymphocytosis settled, the dactylitis and pain resolved. There was no return of symptoms at two year follow up, although the lymphocytosis has re-emerged. This patient’s lymphocytosis was due to early stage CLL. This is common in the elderly, usually incidental and asymptomatic. There are reports of arthritis associated with CLL, but dactylitis has not previously been described. Competing interests: None declared Editorial note The patient whose case is described has given her signed informed consent to publication.