C. Bunch

FREQUENCY OF SEVERE NEUTROPENIA ASSOCIATED WITH AMODIAQUINE PROPHYLAXIS AGAINST MALARIA

6 out of 7 patients with severe neutropenia associated with the use of amodiaquine for malaria prophylaxis amodiaquine (400 mg weekly) plus proguanil (200 mg daily); 1 of these patients had also taken cotrimoxazole and another had taken sulphaguanidine. The 7th patient had taken amodiaquine alone, but at a higher dose. A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000.

Predictors of infection in chronic lymphocytic leukaemia (CLL).

A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2‐year period. A group of 56 healthy age‐matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P=8.8 × 10−11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P=4.9 × 10−4). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P= <0.00001).

Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes

Summary. Previous studies have shown that intravenous immunoglobulin (IVIg) therapy is useful prophylaxis against infection in patients with secondary hypogammaglobulinaemia due to a low‐grade lymphoproliferative disease. This randomized double‐blind study was undertaken to determine prospectively the dose regime required. 34 such patients received IVIg at either 500 or 250 mg/kg every 4 weeks for 1 year. There was no significant difference in the rates of serious infections between the two groups of patients, which were well matched for disease and laboratory parameters. The rates of infection seen were similar to those in IVIg groups of previous studies and strikingly different from those in the placebo group in the previously randomized placebo‐controlled study.

Demonstration of developing myelodysplasia/acute myeloid leukaemia in haematologically normal patients after high‐dose chemotherapy and autologous bone marrow transplantation using X‐chromosome inactivation patterns

Autologous bone marrow or peripheral blood stem cell transplantation may carry an increased risk of secondary myelodysplasia (MDS) and acute myeloid leukaemia (AML), which are already recognized as complications of conventional treatment for lymphoid malignancies. In order to ascertain whether it is possible to detect the evolution of such a clone at an early stage in its development we have studied X‐chromosome inactivation patterns (XCIPs) in three informative females who developed abnormal myelopoiesis after high‐dose chemotherapy and ABMT. In one patient transplanted for relapsed Hodgkins disease a leukaemic clone comprising approximately 50% of the patients myeloid cells was detectable by comparison of peripheral blood granulocyte and T‐cell XCIPs when the full blood count and morphology were normal. She presented with AML 7 months later. In two patients transplanted for AML, XCIP analysis was complicated by constitutively skewed Lyonization patterns, nevertheless a progressive alteration could be demonstrated by serial analyses. In one patient a difference was detectable 28 months before presentation with MDS. In the other patient, despite evident mild pancytopenia and alterations in her XCIPs over the past 4 years, she has developed no definitive myelodysplastic features and oligoclonality due to stem cell failure cannot be excluded. These studies show that XCIPs can be used to predict development of MDS/AML in some patients, but the technique is limited by technical variability and frequent constitutional skewing in the haemopoietic system.

Anti‐granulocyte opsonic activity in sera from patients with systemic lupus erythematosus

Neutropenia is common in patients with systemic lupus erythematosus (SLE) but mechanisms of cell depletion remain obscure. To investigate the possible autoimmune aetiology of neutropenia in SLE, sera from 31 patients with this disorder were tested for anti‐granulocyte activity. Granulocyte‐binding immunoglobulins were detected by indirect immunofluorescence, and the ability of patient sera to opsonize granulocytes was determined by measuring the chemiluminescent response of human monocytes to granulocytes sensitized by test sera.

Anti-granulocyte opsonic activity and autoimmune neutropenia.

Sera from patients with unexplained neutropenia have been assayed for anti‐granulocyte opsonic activity using a chemiluminescence technique which measures the metabolic response of human monocytes to antibody‐coated granulocytes. This rapid and simple technique was more sensitive than indirect immunofluorescence in the detection of anti‐granulocyte antibodies.

Streptococcus mutans infective endocarditis complicated by vertebral discitis following dental treatment without antibiotic prophylaxis.

We report what we believe is the first reported case of Streptococcus mutans endocarditis complicated by vertebral discitis. The case is particularly interesting and topical as it occurred in a patient with pre-existing cardiac valvular disease who had recently had a dental procedure without antibiotic prophylaxis following a dramatic shift in the UK guidelines.

Hypogammaglobulinaemia in Low Grade B Cell Tumours; Significance and Therapy

Bacterial infection is an important cause of morbidity and mortality in patients with B-cell tumors; this is related to their secondary hypogammaglobulinaemia. Two studies of intravenous replacement therapy [IVIg] have been performed in such patients: a crossover study over two years and a randomised, multicentre study over one year. Both involved infusions of IVIg [400 mg/Kg] or an equivalent volume of saline every three weeks for one year. In both studies, serious bacterial infections were considerably reduced by IVIg. Viral and fungal infections were uncommon. In the crossover study bacterial infections were more frequent in periods in which patients serum IgG levels were below the normal range [less than 6.4 g/l]. The sites of bacterial infection were similar in these studies to those in previously published reports, namely respiratory tract, skin, urinary tract and blood. There were a few mild adverse reactions which were related to the rate of infusion, but no serious toxic effects. Haematological parameters were not significantly changed by IVIg at this dose and disease progression did not appear to be changed.