Martin R. Howard

Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients.

Summary. The true incidence and prognosis of autoimmune thrombocytopenic purpura (ITP) in adults is unknown. We present the results of a prospective study in a population‐based cohort of newly presenting adults (≥ 16 years) with ITP and platelet count of < 50 × 109/l, which took place between 1 January 1993 and 31 December 1999 in the former Northern Health Region in the UK (population 3·08 million). A total of 245 cases were confirmed by bone marrow examination with a median follow‐up of 60 months (range 6–78 months). There were 134 females/111 males (1·2:1). Overall incidence was 1·6 per 105 per annum. Absolute incidence was similar for both sexes, with highest age‐specific incidence in those aged > 60 years. Thirty patients (12%) presented with frank bleeding, and 28% were asymptomatic. Forty‐five patients (18%) received no treatment, and 135 (55%) received first‐line treatment only. Thirty patients (12%) underwent splenectomy. There were four deaths (1·6%) from bleeding and/or the complications of therapy in this cohort, but only one was in the acute phase of the illness. The majority of patients (155 out of 245) achieved remission (platelet count > 100 × 109/l), with a further 59 (24%) in partial remission with no symptoms (platelet count 30–100 × 109/l). This population‐based study suggests that the traditional view of adult ITP as being a predominantly chronic disease that preferentially affects females needs to be modified.

Haematological malignancy: are patients appropriately referred for specialist palliative and hospice care? A systematic review and meta-analysis of published data

Haematological malignancies are complex diseases, affecting the entire age spectrum, and having marked differences in presentation, treatment, progression and outcome. Patients have a significant symptom burden and despite treatment improvements for some sub-types, many patients die from their disease. We carried out a systematic review and meta-analysis to examine the proportion of patients with haematological malignancies that received any form of specialist palliative or hospice care. Twenty-four studies were identified, nine of which were suitable for inclusion in the meta-analysis. Our review showed that patients with haematological malignancies were far less likely to receive care from specialist palliative or hospice services compared to other cancers (Risk Ratio 0.46, [95% confidence intervals 0.42–0.50]). There are several possible explanations for this finding, including: ongoing management by the haematology team and consequent strong bonds between staff and patients; uncertain transitions to a palliative approach to care; and sudden transitions, leaving little time for palliative input. Further research is needed to explore: transitions to palliative care; potential unmet patient needs; where patients want to be cared for and die; existing practices in the delivery of palliative and end-of-life care; and barriers to specialist palliative care and hospice referral and how these might be overcome.

Destined to die in hospital? Systematic review and meta-analysis of place of death in haematological malignancy

BackgroundHaematological malignancies are a common, heterogeneous and complex group of diseases that are often associated with poor outcomes despite intensive treatment. Research surrounding end-of-life issues, and particularly place of death, is therefore of paramount importance, yet place of death has not been formally reviewed in these patients.MethodsA systematic literature review and meta-analysis was undertaken using PubMed to identify all studies published between 1966 and 2010. Studies examining place of death in adult haematology patients, using routinely compiled morbidity and mortality data and providing results specific to this disease were included. 21 studies were identified with descriptive and/or risk-estimate data; 17 were included in a meta-analysis.ResultsCompared to other cancer deaths, haematology patients were more than twice as likely to die in hospital (Odds Ratio 2.25 [95% Confidence Intervals, 2.07-2.44]).ConclusionHome is generally considered the preferred place of death but haematology patients usually die in hospital. This has implications for patients who may not be dying where they wish, and also health commissioners who may be funding costly end-of-life care in inappropriate acute hospital settings. More research is needed about preferred place of care for haematology patients, reasons for hospital deaths, and how these can be avoided if home death is preferred.

What determines referral of UK patients with haematological malignancies to palliative care services? An exploratory study using hospital records

We investigated the frequency and characteristics of patients with haematological malignancies (HMs) who were, or were not, referred for specialist palliative care (SPC). Data were abstracted from hospital records of 108 patients who died — 27 with leukaemia, 11 with myelodysplastic syndromes, 48 with lymphoma and 22 with myeloma. Ninety-three patients (86.1%) were >60 years of age at diagnosis, with 33 (30.6%) being ≥80 years and 31 (28.7%) having existing comorbidities. Thirty-three patients (30.6%) were referred to SPC services. There was little difference by age or HM diagnosis in referred patients. Seventeen of 67 patients (25.4%) dying on a hospital ward received SPC compared with 6/7 (85.7%) dying at home. Time between diagnosis and death influenced the referral — 24/52 patients (46.2%) dying ≥30 days after diagnosis received SPC compared with 8/42 (19.1%) dying within 30 days. In 14 patients, HM diagnosis was confirmed after death. Identification of these 14 patients is likely to be a unique feature of our study, as patients were selected from a regional, population-based register with centralized diagnostic services, enabling the identification of all patients with HM. The interface between curative and palliative treatment in HM is more complex than the National Institute for Clinical Excellence recommendations suggest. Palliative Medicine 2007; 21 : 487—492

Regional transfusion centre preoperative autologous blood donation programme: the first two years.

OBJECTIVE--To assess the efficacy of a regional autologous blood donation programme. DESIGN--Clinical and laboratory data were collected and stored prospectively. Transfusion data were collected retrospectively from hospital blood bank records. SETTING--Northern Region Blood Transfusion Service and 14 hospitals within the Northern Regional Health Authority. SUBJECTS--505 patients referred for autologous blood donation before elective surgery. MAIN OUTCOME MEASURES--Patient eligibility, adverse events from donation, autologous blood units provided, and autologous and allogeneic blood units transfused within 10 days of operation. RESULTS--Of 505 patients referred, 354 donated at least one unit. 78 of 151 referred patients who did not donate were excluded at the autologous clinic, mostly because of anaemia or ischaemic heart disease. In 73 cases the patient, general practitioner, or hospital consultant decided against donation. 363 autologous procedures were undertaken. In 213 (59%) cases all requested units were provided. The most common reasons for incomplete provision were late referral or anaemia. Adverse events accompanied 24 of 928 donations (2.6%). Transfusion data were obtained for 357 of the 363 procedures. 281 donors were transfused; autologous blood only was given to 225, autologous and allogeneic blood was given to 52, and allogeneic blood only was given to four. 648 of 902 (72%) units of autologous blood were transfused. Complete provision of requested autologous units was followed by allogeneic transfusion in 12 of 208 procedures (5.8%). Incomplete provision was followed by allogeneic transfusion in 44 of 149 procedures (30%). CONCLUSIONS--This study shows the feasibility of a regional autologous transfusion programme. Autologous donors only infrequently received allogeneic transfusion. Patients should be appropriately selected and referred early.

Variations in specialist palliative care referrals: findings from a population-based patient cohort of acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma

Objective To develop and implement a methodology for capturing complete haematological malignancy pathway data and use it to identify variations in specialist palliative care (SPC) referrals. Methods In our established UK population-based patient cohort, 323 patients were diagnosed with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma between May 2005 and April 2008, and died before April 2010. A day-by-day calendar approach was devised to collect pathway data, including SPC referrals, to supplement routinely collected information on clinical presentation, diagnosis, treatment, response, and date and place of death. Results 155 (47.9%) of the 323 patients had at least one SPC referral. The likelihood of referral increased with survival (OR 6.58, 95% CIs 3.32 to 13.03 for patients surviving ≥1 year compared to ≤1 month from diagnosis), and varied with diagnosis (OR 1.96, CIs 1.15 to 3.35 for myeloma compared to acute myeloid leukaemia). Compared to patients dying in hospital, those who died at home or in a hospice were also more likely to have had an SPC referral (OR 3.07, CIs 1.59 to 5.93 and 4.74, CIs 1.51 to 14.81, respectively). No associations were found for age and sex. Conclusions Our novel approach efficiently captured pathway data and SPC referrals, revealing evidence of greater integration between haematology and SPC services than previously reported. The likelihood of referral was much higher among those dying outside hospital, and variations in practice were observed by diagnosis, emphasising the importance of examining diseases individually.

Preferred and actual place of death in haematological malignancy

Objectives Home is considered the preferred place of death for many, but patients with haematological malignancies (leukaemias, lymphomas and myeloma) die in hospital more often than those with other cancers and the reasons for this are not wholly understood. We examined preferred and actual place of death among people with these diseases. Methods The study is embedded within an established population-based cohort of patients with haematological malignancies. All patients diagnosed at two of the largest hospitals in the study area between May 2005 and April 2008 with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma, who died before May 2010 were included. Data were obtained from medical records and routine linkage to national death records. Results 323 deceased patients were included. A total of 142 (44%) had discussed their preferred place of death; 45.8% wanted to die at home, 28.2% in hospital, 16.9% in a hospice, 5.6% in a nursing home and 3.5% were undecided; 63.4% of these died in their preferred place. Compared to patients with evidence of a discussion, those without were twice as likely to have died within a month of diagnosis (14.8% vs 29.8%). Overall, 240 patients died in hospital; those without a discussion were significantly more likely to die in hospital than those who had (p≤0.0001). Of those dying in hospital, 90% and 75.8% received haematology clinical input in the 30 and 7 days before death, respectively, and 40.8% died in haematology areas. Conclusions Many patients discussed their preferred place of death, but a substantial proportion did not and hospital deaths were common in this latter group. There is scope to improve practice, particularly among those dying soon after diagnosis. We found evidence that some people opted to die in hospital; the extent to which this compares with other cancers is of interest.

Outreach monitoring service for patients with indolent B-cell and plasma cell disorders: a UK experience.

Disease progression occurs in over 1% of monoclonal gammopathy of undetermined significance, monoclonal B‐cell lymphocytosis and early stage chronic lymphocytic leukaemia patients every year therefore regular monitoring is indicated. We assessed the efficacy of an outreach service to replace clinic monitoring using local phlebotomy with central haematologist review of laboratory parameters and symptoms identified by a patient self‐assessment questionnaire. The service was used by 299 patients for 2 years and provided accurate monitoring, improved patient satisfaction, support for primary care and reduced the burden on haematology clinics without an increase in inter‐assessment admissions due to disease progression.

Alpha interferon gene deletions in post-transplant lymphoma

Post‐transplant lymphoproliferative disorder (PTLD) is a well‐recognized complication of organ transplant and has been associated with high mortality using conventional chemotherapy. We have investigated 11 cases of PTLD for alterations to the interferon alpha (IFNA) and p16 genes on chromosome 9p using archival material. 4/9 (44%) cases had deletions of the IFNA genes, in contrast to 1/59 (1.7%) cases of intermediate/high‐grade de novo NHL drawn from the same geographical region. PTLD may therefore represent a distinct NHL subgroup exhibiting distinct gene pathology.

Skin lésions in plasmacytoid dendritic cell leukaemia

A 76-year-old previously fit and healthy man presented with a 6-month history of lethargy, dyspnoea and anorexia. On examination, he had two discoid erythematous skin lesions measuring 3 cm in diameter, one on his left cheek and one on his chest (top left). There was also a more generalized erythematous rash on his left thigh and back (bottom left). There was no lymphadenopathy or hepatosplenomegaly. His full blood count on presentation showed a severe anaemia and thrombocytopenia (haemoglobin 63 g/l, white blood cell count 5Æ4 · 10/l, platelet count 80 · 10/l). His blood film showed hypogranular neutrophils, anisopoikilocytosis and 10% atypical blast-like cells, which were subsequently shown to be plasmacytoid dendritic cells. A bone marrow slide (right) showed replacement with small to medium-sized blasts with eccentric nuclei and grey-blue cytoplasm with pseudopods. Flow cytometry showed blasts positive for CD4 and CD56, but negative for cCD3, CD19, CD20, CD13, CD33 and cMPO (also CD45dimCD34CD15CD117HLADR + CD7CD14 CD64 CD2NG2/, CD38,CD66cCD58CD10cCD79a, CD123). The co-expression of CD4 and CD56 in the absence of the above-mentioned T-, B-cell and myeloid markers corresponded to the diagnosis of plasmacytoid dendritic cell leukaemia. Skin lesions are typical of this disease. In this rare haematological malignancy complete remission can be obtained with differing regimens of chemotherapy in three quarters of patients, but relapse is usual within 2 years unless bone marrow transplant is undertaken. This patient was started on CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) as his physical condition precluded the use of more intensive regimens. A bone marrow biopsy on day 22 of the first cycle has confirmed complete remission.