Quentin A. Hill

Intensify, resuscitate or palliate: Decision making in the critically ill patient with haematological malignancy

The survival prospects of critically ill patients with haematological malignancy (HM) are reviewed, as are the variables which might influence decisions about the limitation of life sustaining therapies (LLST). Approximately 40% of patients with HM admitted to ICU survive to hospital discharge and a broad admission policy is warranted. Short term survival is predicted by the severity of the underlying physiological disturbance rather than cancer specific characteristics, although the prognostic importance of neutropenia and prior stem cell transplantation remains to be clarified. Survival to hospital discharge in cancer patients following cardio-pulmonary resuscitation (CPR) is only 6-8%. Poor performance status and progressive deterioration despite ICU support appear to predict worse outcome. Patients should be provided with realistic information in order to make an informed decision about CPR. Decisions about LLST must be individualised. Consideration should be given to the patients wishes and prognosis, the immediate clinical circumstances and their potential reversibility.

Outcome prediction in plasmacytoma of bone: a risk model utilizing bone marrow flow cytometry and light-chain analysis

The purpose of this study was to use multiparameter flow cytometry to detect occult marrow disease (OMD) in patients with solitary plasmacytoma of bone and assess its value in predicting outcome. Aberrant phenotype plasma cells were demonstrable in 34 of 50 (68%) patients and comprised a median of 0.52% of bone marrow leukocytes. With a median follow-up of 3.7 years, 28 of 50 patients have progressed with a median time to progression (TTP) of 18 months. Progression was documented in 72% of patients with OMD vs 12.5% without (median TTP, 26 months vs not reached; P = .003). Monoclonal urinary light chains (ULC) were similarly predictive of outcome because progression was documented in 91% vs 44% without (median TTP, 16 vs 82 months; P < .001). By using both parameters, it was possible to define patients with an excellent outcome (lacking both OMD and ULC, 7.7% progression) and high-risk patients (OMD and/or ULC, 75% progression; P = .001). Trials of systemic therapy are warranted in high-risk patients.

Survival of patients with hematological malignancy admitted to the intensive care unit: prognostic factors and outcome compared to unselected medical intensive care unit admissions, a parallel group study

Abstract Improved survival in patients with hematological malignancy (HM) admitted to the intensive care unit (ICU) has largely been reported in uncontrolled cohorts from single academic institutions. We compared hospital mortality between 147 patients with HM and 147 general medical admissions to five non-specialist ICUs. The proportion of patients surviving to hospital discharge was significantly worse in patients with HM (27% vs. 56%; p < 0.001). Six-month and 1-year survival in patients with HM was 21% and 18%, respectively. HM, greater age, mechanical ventilation (MV) and acute physiology and chronic health evaluation (APACHE) II score were independent predictors of poor outcome. For patients with HM, culture proven infection, age, MV and inotropes were negative predictors. Disease-specific factors including hematological diagnosis, neutropenia, remission status, prior stem cell transplant, time from diagnosis to admission and degree of prior treatment were not predictive. Overall survival of patients with HM was worse than that recently reported from specialist units.

The diagnosis and management of primary autoimmune haemolytic anaemia

The objective of this guideline is to provide healthcare professionals with guidance on the management of patients with primary autoimmune haemolytic anaemia (AIHA). The guidance may not be appropriate to every patient and in all cases individual patient circumstances may dictate an alternative approach. Attempts to categorise autoimmune haemolytic anaemia (AIHA) and define its response to treatment vary considerably in the published literature. Author defined criteria have been used in this guideline, but this limits study comparisons and will have contributed to differences in reported outcome. The investigation and diagnosis of adult and paediatric AIHA are considered together. Guidance on the treatment of adult AIHA is then followed by a section on paediatric AIHA.

An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF

Increasing demand on the apheresis service makes efficient harvesting of peripheral blood stem cells (PBSCs) essential. A total of 168 adult patients with haematological malignancy were primed using low–moderate dose cyclophosphamide (1.5–3u2009g/m2) with G-CSF 5–10u2009μg/kg per day. Harvesting was booked and peripheral blood (PB) counts first checked between 6 and 10 days post-priming. One hundred and thirty (77%) patients harvested successfully (total harvest yield ⩾2 × 106 CD34+/kg) and the median PBSC collection per procedure was 2.18 × 106/kg (range 0.1–14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34+ cell count correlated significantly with harvest yield (r=0.8448, P<0.0001). A PB CD34+ count ⩾10/μl predicted a collection of ⩾2 × 106/kg (positive-predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6–8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34+ count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service.

Fatigue in immune thrombocytopenia.

Fatigue is an important aspect of health‐related quality of life from the patient perspective and can have significant socio‐economic consequences. It is a common feature of chronic illnesses and a significant number of both adults and children with immune thrombocytopenia (ITP) suffer from fatigue. Reliable, validated fatigue scales have been developed for use in ITP. These will facilitate future investigation of its pathogenesis and the effectiveness of intervention. Acute inflammation acts on neural and endocrine systems resulting in ‘sickness behaviour’, an adaptive response to infection and injury. Inflammation is also thought to cause fatigue in chronic disease and immune dysregulation in ITP appears to have a number of pro‐inflammatory components. Clinicians should consider fatigue when assessing the burden of disease. Although effective ITP‐directed therapy can improve fatigue, a number of fatigue‐directed strategies may also need to be considered.

Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of <5% (range, <5%-18%). The mortality rate was 10.3% (n = 32); 68% of patients had a raised troponin at presentation conferring a sixfold increase in mortality compared with those with normal troponin levels (12.1% vs 2.0%, P = .04). Twenty-four percent had a reduced Glasgow Coma Score (GCS) at presentation with a ninefold increase in mortality (20% vs 2.2% for normal GCS at presentation, P < .0001). Mortality increased with higher anti-ADAMTS13 antibody levels and lower ADAMTS13 antigen levels. Those with antibody levels in the upper quartile (antibody >77%) had a mortality of 16.9% compared with 5.0% for the lowest quartile (antibody <20%) (P = .004). Those with an antigen level in the lowest quartile (antigen <1.5%) had a mortality of 18% compared with 3.8% for the highest quartile (antigen >11%) (P = .005). The synergistic effect of anti-ADAMTS13 IgG antibody in the upper quartile and ADAMTS13 antigen in the lowest quartile had the highest mortality of 27.3%. We conclude that both anti-ADAMTS13 IgG antibody and ADAMTS13 antigen levels correlate with outcome in TTP with increased cardiac and neurological involvement and increased mortality.

Obstructive Jaundice Due to a Pancreatic Mass: A Rare Presentation of Acute Lymphoblastic Leukaemia in an Adult

CONTEXTnTo highlight a rare presentation of acute lymphoblastic leukaemia.nnnCASE REPORTnA 39-year-old man presented with a 4 month history of weight loss and a 6 week history of upper abdominal pain radiating to the back with nausea and vomiting. Liver function tests showed an obstructive picture, full blood count was normal and on computerised tomography there was diffuse enlargement of the pancreas, with dilatation of the common bile duct and intra hepatic biliary radicles. Four weeks after presenting, the white cell count became elevated with blasts on the blood film and bone marrow biopsy revealed a precursor B cell acute lymphoblastic leukaemia. After induction chemotherapy his jaundice resolved, the pancreatic mass reduced in size and he is now in a complete remission.nnnCONCLUSIONnAcute lymphoblastic leukaemia may mimic common causes of a pancreatic mass such as adenocarcinoma and should be considered as part of the differential diagnosis when atypical features are present.

Autoimmune haemolytic anaemia

Autoimmune haemolytic anaemia (AIHA) can be classified as warm or cold type and may be either idiopathic (primary) or secondary to haematological malignancy, infection or other conditions that result in immune dysregulation. Presentation can vary from the gradual onset of symptomatic anaemia, to an acute fulminant episode of life‐threatening haemolysis. Management, which is not evidence based, largely entails the use of initial corticosteroids for primary warm‐type AIHA with either splenectomy, rituximab or alternative immunosuppression for those requiring second‐line therapy. Rituximab is now considered a first‐line therapy for primary cold haemagglutinin disease. Transfusion may be needed as a supportive measure particularly with severe acute haemolysis and requires close liaison between clinical and laboratory teams to ensure appropriate selection of red cell units in a timely manner.

How does dapsone work in immune thrombocytopenia? Implications for dosing

To the editor:nnDapsone is a standard second-line treatment of primary immune thrombocytopenia (ITP), with response rates of 27% to 63%. Most adult studies used 100 mg daily, but the rationale for dose selection is unclear, and no ITP study has sought an association between dose and response.