Nauman M. Butt

Guideline for investigation and management of adults and children presenting with a thrombocytosis.

Guy’s and St Thomas’ NHS Foundation Trust, London, Russells Hall Hospital, Dudley, West Midlands, Arrowe Park Hospital Arrowe Park Road Upton Wirral, Wellcome Trust Sanger Institute, Hinxton, Cambridge, St. James Hospital, James Street, Dublin, Gartnavel General Hospital 21 Shelley Road Glasgow, Addenbrooke’s Hospital, Cambridge, Salisbury Healthcare NHS Trust, Salisbury, Wiltshire, Cambridge Institute for Medical Research, Hills Road, Cambridge, John Radcliffe Hospital, Headley Way, Headington, Oxford, Royal Infirmary, Little France Crescent, Edinburgh, Sandwell and West Birmingham Hospitals, Dudley Road, Birmingham, Royal Hallamshire Hospital, Glossop Road, Sheffield, and Belfast City Hospital, Lisburn Road Belfast, UK

A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials

A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials

Guideline for the diagnosis and management of myelofibrosis

The guideline group regarding the diagnosis and management of myelofibrosis was selected to be representative of UK‐based medical experts, together with a contribution from a single expert from the USA. MEDLINE and EMBASE were searched systematically for publications in English from 1966 until August 2011 using a variety of key words. The writing group produced the draft guideline, which was subsequently revised by consensus of the members of the General Haematology and Haemato‐oncology Task Forces of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The criteria used to state levels and grades of evidence are as outlined in the Procedure for Guidelines commissioned by the BCSH; the ‘GRADE‘ system was used to score strength and quality of evidence. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of primary myelofibrosis, as well as post‐polycythaemic myelofibrosis (post‐PV MF) and post‐thrombocythemic myelofibrosis (post‐ET MF) in both adult and paediatric patients.

Use of JAK inhibitors in the management of myelofibrosis: a revision of the British Committee for Standards in Haematology Guidelines for Investigation and Management of Myelofibrosis 2012

Reilly, John T., McMullin, Mary Frances, Beer, Philip A., Butt, Nauman, Conneally, Eibhlin, Duncombe, Andrew S., Green, Anthony R., Mikhaeel, George, Gilleece, Marie H., Knapper, Steven, Mead, Adam J., Mesa, Ruben A., Sekhar, Mallika and Harrison, Claire N. 2014. Use of JAK inhibitors in the management of myelofibrosis: a revision of the British Committee for Standards in Haematology Guidelines for Investigation and Management of Myelofibrosis 2012. British Journal of Haematology 167 (3) , pp. 418-420. 10.1111/bjh.12985 file

Modification of British Committee for Standards in Haematology diagnostic criteria for essential thrombocythaemia

The diagnosis of the myeloproliferative neoplasms (MPN)‒ essential thrombocythaemia (ET) and primary myelofibrosis (PMF) ‒ in patients lacking a molecular marker is challenging. Recently, mutations in exon 9 of the calreticulin gene (CALR) have been described in around one-third of ET and MF patients (Klampfl et al, 2013a; Nangalia et al, 2013). Notably, these mutations are almost always seen in JAK2 V617F-negative and MPL-non-mutated patients and account for the majority of these cases. Such is the prevalence of these mutations we suggest that they are added to the British Committee for Standards in Haematology criteria for the diagnosis of ET and also PMF (Harrison et al, 2010; Reilly et al, 2012) (evidence grade 1A). The modified diagnostic criteria and algorithms are shown in

Guideline for the investigation and management of eosinophilia

Nauman M. Butt, Jonathan Lambert, Sahra Ali, Philip A. Beer, Nicholas C. P. Cross, Andrew Duncombe, Joanne Ewing, Claire N. Harrison, Steven Knapper, Donal McLornan, Adam J. Mead, Deepti Radia, and Barbara J. Bain on behalf of the British Committee for Standards in Haematology Royal Liverpool and Broadgreen University Teaching Hospitals NHS Trust, Liverpool, University College London Hospitals NHS Foundation Trust, London, Hull and East Yorkshire Hospitals NHS Trust, Hull, Wellcome Trust Sanger Institute, Cambridge, Faculty of Medicine, University of Southampton, Department of Haematology, University Hospital Southampton, Southampton, Heart of England NHS Foundation Trust, Birmingham, Guy’s and St Thomas’ NHS Foundation Trust, London, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff, King’s College Hospital NHS Foundation Trust, London, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and BRC Blood Theme, NIHR Oxford Biomedical Centre, Oxford, and Imperial College London, St Mary’s Hospital, London, UK

A population study showing that the advent of second generation tyrosine kinase inhibitors has improved progression-free survival in chronic myeloid leukaemia

BACKGROUND Population based data suggest the proportion of patients failing imatinib in chronic myeloid leukaemia (CML) is higher than the reported one-third of patients in clinical trials. Clinical trials have demonstrated second generation tyrosine kinase inhibitors (TKI) dasatinib and nilotinib can restore complete cytogenetic remission (CCR) and major molecular response (MMR) to many patients failing imatinib, but their impact in the general population is not clear. DESIGN AND METHODS We report CML outcome in a population of 2.3 million people in a geographically contiguous area of North West England and North Wales. RESULTS Between 2003 and 2009, 192 new CML cases were diagnosed, of whom 184 were in chronic phase and 160 started on imatinib. The maximal CCR rate was 65% at 24 months and the maximal MMR rate was 50% at 36 months. Patients diagnosed since second generation TKI became available for imatinib failure had a more rapid cumulative CCR and MMR rate and a significantly improved progression free survival (p=0.022) than those diagnosed before this time. CONCLUSION The study indicates that second generation TKI have improved CML outcome in the general population.

Diagnostic pathway for the investigation of thrombocytosis

Additional Supporting Information may be found in the online version of this article: Fig S1. Forward DNA sequences of the region surrounding RHAG codon 65. All sequences represent genomic DNA except for the cDNA sequence from patient II:1 (right lower panel). Right middle panel genomic sequence II:1 (S/S in red italics) was from the RHAG exon 2 PCR amplicon produced with oligonucleotide primer “I3R1,” which encompasses intronic SNP rs9473627 (c.22956G>C; 29% minor allele frequency).

High frequency of positive surveillance for cytomegalovirus (CMV) by PCR in allograft recipients at low risk of CMV

Cytomegalovirus (CMV) causes significant morbidity and mortality following allogeneic haemopoietic stem cell transplantation. A pre-emptive strategy for ganciclovir therapy is widely used, where treatment is commenced on finding positive evidence of CMV replication. Surveillance by PCR has increased the sensitivity for CMV detection, but it is not known whether this may detect cases with evidence of CMV DNAemia who have a low probability of CMV disease. We reviewed our experience of CMV infection and disease since introducing CMV surveillance by PCR. All 30 allografts received bedside leucodepleted CMV-negative blood products. Seven of 10 CMV-positive recipients of a CMV-positive graft developed CMV DNAemia, with three developing clinical disease requiring ganciclovir treatment. In contrast, of 11 low risk patients (CMV-negative recipients of CMV-negative grafts), six developed evidence of CMV DNAemia although only one had clinical evidence of CMV disease requiring ganciclovir. Transfusion records confirmed that four of these had received exclusively CMV-negative blood products. The aetiology of the CMV DNAemia in these cases is unclear. It is suggested that before commencing ganciclovir therapy, confirmatory CMV antigenaemia testing is carried out on samples which test positive for CMV DNA, unless there is high clinical suspicion of CMV disease. Bone Marrow Transplantation (2001) 27, 615–619.

CD34 Positive Selection as Prophylaxis Against Graft Versus Host Disease in Allogeneic Peripheral Blood Stem Cell Transplantation

We report our experience of CD34 positive selection as a means of graft T-cell depletion (TCD) in 14 consecutive HLA-identical Peripheral blood stem cells (PBSC) allografts as prophylaxis against graft versus host disease (GVHDp). CD34 positive selection was performed by immunomagnetic separation achieving a median CD34 and T-cell dose of 4.17 (range 1.4–8.50) × 106/kg and 1.89 (range 0.92–13.18) × 104/kg, respectively, in the graft. This represents 4-log depletion of T-cells. The median time to achieve a neutrophil count of 0.5 × 109/l was 15 days and to achieve a platelet count of 50 × 109/l was 20 days. Only four patients developed acute GVHD at a median of 41 days but this was exclusively mild grade I cutaneous disease and settled with oral steroids. Four patients, all of whom had AML, relapsed or progressed after transplant at a median of 161 (range 109–311) days. One of these had been transplanted in early relapse (9% blasts) whilst another was in second remission. The remaining 10 patients are alive and well. The median progression free survival for the whole population is 69% at 686 days. We conclude that CD34 positive selection by immunomagnetic separation in HLA-identical PBSC allografting achieves significant TCD with clinically trivial acute GVHD, prompt engraftment and an acceptable disease relapse risk.