Alemtuzumab is a humanized anti-CD52 antibody licensed for refractory B-cell chronic lymphocytic leukemia (B-CLL), when given intravenously at 30 mg thrice weekly. However, the intravenous route is associated with infusion-related reactions and is inconvenient. We measured blood concentrations in 30 relapsed patients treated with intravenous alemtuzumab and in 20 patients from a previously untreated group who received similar doses subcutaneously. Highest trough samples in the intravenous group were less than 0.5 microg/mL to 18.3 microg/mL (mean 5.4 microg/mL). The cumulative dose required to reach 1.0 microg/mL was 13 mg to 316 mg (mean 90 mg). Higher blood concentrations correlated with the achievement of better clinical responses and minimal residual disease. The highest measured concentrations in the subcutaneous group were similar (0.6 microg/mL to 24.8 microg/mL, mean 5.4 microg/mL). However, the cumulative dose to reach 1.0 microg/mL was higher: 146 mg to 1106 mg (mean 551 mg). No antiglobulin responses were detected in 30 patients given intravenous alemtuzumab whereas 2 of 32 patients given subcutaneous alemtuzumab made substantial anti-idiotype responses. Thus, subcutaneous alemtuzumab achieved concentrations similar to those for intravenous alemtuzumab, although with slightly higher cumulative doses. Subcutaneous alemtuzumab is more convenient and better tolerated but may be associated with some patients forming anti-alemtuzumab antibodies, particularly those patients who were previously untreated.

Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. 32 We therefore evaluated whether complement defects in CLL patients reduced the induction of 33 complement-dependent cytoxicity (CDC), using anti-CD20 MAbs rituximab (RTX) and ofatumumab 34 (OFA). OFA elicited higher CDC levels than RTX in all CLL samples examined, particularly the poor 35 prognosis cohorts (11q-and 17p-). Serum sample analyses revealed 38.1% of patients were deficient 36 in one or more complement components, correlating with reduced CDC responses. While a proportion 37 of patients with deficient complement levels initially induced high levels of CDC, on secondary 38 challenge CDC activity in sera was significantly reduced, compared with normal human serum (NHS; 39 p<0.01; n=52). Additionally, high CLL cell number contributed to rapid complement exhaustion. 40 Supplementing CLL serum with NHS or individual complement components, particularly C2, restored 41 CDC on secondary challenge to NHS levels (p<0.0001; n=9). In vivo studies revealed that 42 complement components were exhausted in CLL patient sera post-RTX treatment, correlating with an 43 inability to elicit CDC. Supplementing MAb treatment with fresh frozen plasma may therefore maintain 44 CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study 45 has important implications for CLL patients receiving anti-CD20 MAb therapy.

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Royal Free London NHS Trust, London, UK Keywords: Hodgkin lymphoma, Hodgkin disease, lymphocyte predominant Hodgkin lymphoma.The guideline group was selected to be representative of UKbased medical experts. Ovid MEDLINE, Ovid EMBASE and DYNAMED were searched systematically for publications in English from 1980 to 2014 using the key words Hodgkin disease, Hodgkin lymphoma and lymphocyte predominant Hodgkin lymphoma. References from relevant publications were also searched. Editorials, studies with <8 cases, letters and conference abstracts were excluded. The writing group produced the draft guideline, which was reviewed by the British Committee for Standards in Haematology (BCSH) Haemato-oncology Task Force. Further comments were invited from a sounding board of the British Society for Haematology (BSH) and patient representatives identified through the Lymphoma Association.

Clinically and biologically, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has much more in common with germinal-centre derived B-cell NHL than classical HL. Management of NLPHL remains controversial. In a 14-year multi-centre series, 69 cases were analysed; median follow-up was 53 months (range 11-165.) B symptoms were present in only 4.3% of patients. 81.1% of patients had stage I/II disease. Treatment was with radiotherapy (53.6 %), chemotherapy (21.7%), combined modality (17.4%) and observation (7.2%.) 10.1% of patients relapsed and 2.9% of patients developed high-grade transformation to DLBCL. All relapses and transformations were salvageable. No patient died of their disease. The 5 yr relapse-free survival was 96.7%, transformation-free survival 98.4% and overall survival 100%. We conclude that NLPHL behaves as a distinct clinical entity, often presenting at early stage without risk factors. It has an excellent outcome. It may be possible to reduce intensity of therapy in NLPHL without affecting OS.

We describe two cases of autoimmune thrombocytopenia precipitated by fludarabine therapy in patients with chronic lymphatic leukaemia. Both were treated with high dose steroids and initially responded with recovery of normal platelet counts. One patient developed recurrent autoimmune thrombocytopenia on two occasions following re-exposure to the drug when his disease had become refractory to all other treatments. A retrospective review of the case notes of 45 patients with lymphoproliferative disorders treated with fludarabine over the past 6 years indicated the development of autoimmune thrombocytopenia in 4.5% (two out of 45) and autoimmune haemolytic anaemia in 6.7% (three of the 45).

The full blood count (FBC) is perhaps the single most common investigation performed in medical patients. It has the potential, when interpreted carefully and in relation to the clinical history, to provide very useful information to assist in diagnosis and management. Clinicians are often alerted to the presence of a primary haematological disorder by abnormalities in the FBC. For the purpose of this review these diseases will not be discussed in detail but the reader will be alerted to pointers which might indicate primary blood disorders throughout the text. The haematology laboratory in large teaching hospitals will often provide up to 1,500 automated FBC analyses each day. These are individually checked for 'flags' provided by the analyser which indicate values outside the normal range. It is clearly essential that clinical information is provided with the request as this will influence how the result is handled by scientific and medical staff. Furthermore, significant abnormalities will generate a blood film request and the report will be most useful when interpreted in light of the patient's working diagnosis. In cases where a diagnosis is not yet known, even brief information on presentation, for example 'collapse with hypotension', 'fever on return to UK', 'weight loss and anorexia', can all be important and help the lab provide clinicians with guidance. This short review aims to provide physicians with a workable guide to the interpretation of some of the commoner findings in the full blood count. Some of these will be very familiar to you but some will not. This review is not meant to be exhaustive as the rare minutiae will obscure the essential core material. Your haematology colleagues are always happy to help and available for assistance in difficult or problematic cases. I have not specified normal ranges in relation to each entity as these will be defined by your local laboratory.