An Ashkenazi Jewish woman presenting with favism.

The case of a 44 year old Ashkenazi Jewish woman of Russian origin who presented with a typical clinical and haematological picture of favism is reported. There was initial difficulty in confirming glucose-6-phosphate dehydrogenase (G6PD) deficiency because the enzyme concentrations were normal at presentation, but later fell to a concentration compatible with heterozygosity for the Mediterranean type of G6PD deficiency. The diagnosis was also later confirmed by gene analysis. The reasons for the difficulties in the initial confirmation of the diagnosis and the normal G6PD enzyme activity at presentation are discussed.

Thalidomide in low doses is effective for the treatment of resistant or relapsed multiple myeloma and for plasma cell leukaemia.

Thalidomide is an effective treatment for relapsed multiple myeloma (MM), but is associated with a significant side effect profile at higher doses. In a recent study, only half of the enrolled patients were able to tolerate the maximum dose of 800 mg/day [Singhal, S., et al. (1999) "Antitumor activity of thalidomide in refractory multiple myeloma", New Engl. J. Med. 341, 1565-1571]. Moreover, the dose-response relationship has not been defined. We report our use of low dose thalidomide in a small cohort of 12 patients-eight with relapsed or refractory MM and four with plasma cell leukaemia (PCL). Five of the 12 (42%) patients had a partial response, showing a median fall in their PP/BJP of 80% (63-90%) at a median dose of 175 mg (100-300 mg) with negligible side effects. Three of four patients with PCL showed an impressive response to treatment with thalidomide as a single agent. No patient who failed to show any evidence of response at low dose (<150 mg/day) responded to higher doses. In this study, thalidomide induces a similar rate of response at a lower and better tolerated dose than previously reported and produced "best ever" responses in patients with resistant PCL.

Multiple myeloma and human immunodeficiency virus-1 (HIV-1) infection.

Multiple myeloma (MM) in three human immunodeficiency virus (HIV)-infected patients is reported. HIV infection predisposes to the development of high-grade B-cell lymphomas, but few cases of plasma cell tumours in association with HIV have been reported. The coincidence of HIV infection and neoplasia highlights the distinct roles of immunodeficiency and infection with herpesviridae, including HIV itself, in the pathogenesis of HIV-related tumours. In addition, a number of cytokines (e.g., interleukin-6 [IL-6]) and angiogenic factors (e.g., vascular endothelial growth factor [VEGF] and basic fibroblastic growth factor [bFGF]) may play a role in the initiation, maintenance, and progression of multiple myeloma (MM). Infection was the first clinical consideration to the cause of the illness in two of our HIV-seropositive patients. The diagnosis of MM may be difficult in patients with advanced HIV infection as they often have renal failure, bone marrow plasmacytosis, repeated infections, and polyclonal hypergammaglobulinaemia, due to HIV infection itself, opportunistic pathogens, and/or medication.

Blood and bone marrow changes in malaria.

A variety of abnormalities in the number, morphology and function of blood and bone marrow cells may be found in Plasmodium falciparum and P. vivax malaria. In a non-immune individual, the nature of such abnormalities depends on the time after infection. In others it is determined by the pattern and intensity of malaria transmission in the area and the extent of host immunity. Severe anaemia may occur in children with chronic falciparum malaria and low parasitaemia as well as in patients with complicated acute falciparum malaria with high parasitaemia. However, the mechanisms underlying the anaemia in these two situations appear to be different. The possible roles of parasite products, T-cell-derived cytokines produced in response to the infection, macrophage activation and hyperplasia, macrophage-derived factors such as tumour necrosis factor-alpha, and macrophage dysfunction in the pathogenesis of the haematological abnormalities are discussed.

Haematological disease in siblings with Rothmund-Thomson syndrome.

We report two siblings with Rothmund-Thomson syndrome (RTS); the older sister died of acute myeloblastic leukaemia and the younger sister has a slowly progressive leucopenia. Her prognosis is guarded in view of the increased incidence of neoplasms in this condition. More than 200 cases of RTS have now been reported worldwide.1 This is the first report of siblings with haematological disease and RTS.

Azathioprine-associated acute myeloid leukaemia with trilineage dysplasia and complex karyotype: a case report and review of the literature.

A 66-year-old female with dermatomyositis (DM) who had received immunosuppressive therapy with azathioprine developed acute myeloid leukaemia (AML). Cytogenetic analysis revealed a complex karyotype including monosomy 7, and trilineage dysplastic features strongly suggestive of a treatment-related aetiology. The literature on azathioprine-associated AML is reviewed.

Thrombocytosis with sideroblastic erythropoiesis: a mixed myeloproliferative myelodysplastic syndrome.

Some patients with haematological neoplasms have features which overlap between a myelodysplastic syndrome and a myeloproliferative disorder. Two such patients are reported, both having sideroblastic erythropoiesis and thrombocytosis and one sequentially developing features of atypical chronic myeloid leukaemia, idiopathic myelofibrosis and acute megakaryoblastic leukaemia. The prevalence of thrombocytosis among cases of refractory anaemia with ring sideroblasts may be as high as 15-20% and has implications for choice of therapy.

Autoimmune haemolytic anaemia associated with dermatomyositis.

We report the case of a female patient who at presentation fulfilled the diagnostic criteria of dermatomyositis and also had an autoimmune haemolytic anaemia. Although autoimmune haemolysis is a well recognized feature of a number of autoimmune disorders, it has not previously been described in association with dermatomyositis.

Detection of mycobacteria in bone marrow biopsy specimens taken to investigate pyrexia of unknown origin.

AIMS: To investigate the value of bone marrow biopsy in the diagnosis of mycobacterial infection. METHODS: The culture results of 433 bone marrow samples taken between 1983 and 1992 were reviewed. The histopathology reports on bone marrow trephine specimens of culture positive samples and all those on HIV positive patients sent in 1992 were also reviewed. RESULTS: Fifty one specimens yielded Mycobacterium spp, 47 were obtained from HIV positive patients. Of the isolates, 42 were Mycobacterium avium-intracellulare (MAI), five were M tuberculosis (MTB), and the remaining four comprised a variety of atypical mycobacteria. All MAI positive samples were obtained from HIV positive patients, with the bone marrow being the only culture positive specimen in one third. Bone marrow yielded MTB only in patients from whom it was also isolated in other specimens. Eleven of 47 trephine specimens from positive bone marrow showed granulomata and nine showed acid-fast bacilli. No acid-fast bacilli were seen in the absence of granulomata. CONCLUSION: Bone marrow biopsy for mycobacterial culture should be reserved for severely immunosuppressed patients and should not be advocated for immunocompetent patients with suspected tuberculosis. Bone marrow biopsy still has a role in the investigation of pyrexia of unknown origin in HIV positive patients, despite the advent of mycobacterial blood culture techniques, particularly if these can be processed safely in automated systems.

Hematopoiesis in human malaria.

This paper presents changes in the bone marrow of patients with malaria; it is based primarily on observations of bone marrows of 89 Gambian children with P. falciparum malaria and includes a review of the literature. Erythroid hyperplasia with dyserythropoiesis was found to be more common in patients with severe anemia and low grade parasitemia than in those with acute malaria. The dyserythropoietic changes are illustrated both with light photomicropraphs and with electron micrographs. The significance of the dyserythropoiesis and possible causes are discussed. Other changes in these patients with acute malaria include lymphocytosis in the bone marrow and reactive lymphocytes, monocytosis and mild neutrophilia in the peripheral blood. Giant metamyelocytes were also commonly seen in bone marrow of patients but were thought to be part of dysmyelopoiesis and not due to B12 or folate deficiency. Phagocytosis of erythrocytes, parasitized cells and nucleated cells was more commonly seen in macrophages in acute malaria, while phagocytosis of small particles such as merozoites was observed in neutrophils. Megakaryocytes were found to be increased in number in patients with acute malaria; a proportion of these cells had rounded nuclei, probably indicating accelerated platelet turnover.

The value of screening tests for glucose-6-phosphate dehydrogenase deficiency.

The performances of two commercial screening tests for glucose-6-phosphate dehydrogenase deficiency (Sigma fluorescent spot test and Sigma colorimetric method) were assessed in order to determine their usefulness in a routine haematology laboratory. As a first step, three ranges for enzyme activity were determined as follows: a 'normal' range determined from the 95% confidence limit of assays carried out on 114 normal adult males, a deficient range calculated as 25% of the upper limit of normal or less, and an intermediate range between the lower and upper values of these ranges. These values were 4.9-11.8 u/g Hb, 0-2.9 u/g Hb and 3.0-4.8 u/g Hb respectively. A separate normal range was also determined for females and was 5.5-12.8 u/g Hb. The two screening tests were then assessed against these values and the kits were found to be equally reliable at predicting normals and deficients but less reliable at detecting all female heterozygotes. The criteria for using the different procedures were evaluated. It is concluded that screening procedures are useful only when a large number of tests are routinely performed or in the absence of facilities for assays, as they offer no advantage in cost or time over the assay procedure. The colorimetric test (single vials) is easier and cheaper to use if isolated tests are performed, whereas the fluorescent spot test (with some modifications) is more useful for carrying out numerous tests simultaneously.

Iron and folate status in Gambian children with malaria.

Iron and folate status were evaluated in a group of 106 Gambian children with malaria and variable degrees of anaemia. In children with malaria, normal or increased levels of red cell folate were found in 75 patients at presentation and in 15 patients 1-2 weeks after treatment with anti-malarials alone, despite the presence of giant metamyelocytes and megaloblasts in the bone marrow in some cases. Twenty-eight per cent of patients were found to have deficient bone marrow iron stores but malaria could not be directly implicated as the cause of this deficiency. Iron deficiency could also not be implicated as the sole cause of dyserythropoiesis in patients with malarial anaemia. Excess storage iron and the presence of ring sideroblasts were found in the bone marrow in some cases. It is concluded that the morphological changes including dyserythropoiesis, occasional megaloblasts, giant metamyelocytes and ring sideroblasts seen in the bone marrows of these children are manifestations of disturbed marrow function in malaria and are not related to haematinic deficiency. Because of the high rate of iron deficiency found in these patients it is recommended that Gambian children with severe anaemia should receive iron therapy after adequate treatment of malaria.

Peripheral blood and bone marrow leucocytes in Gambian children with malaria: numerical changes and evaluation of phagocytosis.

Neutrophilia, monocytosis, eosinopenia and reactive lymphocytes were found in the peripheral blood of infants and children with acute malaria at presentation. These changes were mostly reversed by days 3 and 7 after starting treatment. Mild rebound eosinophilia was seen in three cases after starting treatment. In patients with low grade malaria and anaemia, peripheral blood counts did not alter significantly after treatment. Two patients with mild eosinophilia at presentation were subsequently found to have strongyloidiasis and the eosinophil count rose markedly in one after treatment of malaria. Bone marrows were hypercellular in all cases. There was a low mean percentage of myeloid precursors in the marrow of all children as compared with the normal. This was due to increased lymphocyte percentage in those with acute malaria and to marked erythroid hyperplasia in those with low grade malaria. Phagocytosis of parasitized and non-parasitized red cells by bone marrow macrophages was seen most frequently in children with high parasitaemias, but erythroblast phagocytosis was more commonly seen in those with low grade malaria. There was no absolute correlation between the presence or absence of erythrophagocytosis in marrow macrophages and the presence or absence of a positive direct antiglobulin test (DAT) in children with malaria. This indicates that immunological mechanisms cannot be implicated as the sole cause of erythrophagocytosis in these bone marrows.

A study of erythroid progenitor cells in the bone marrow of Gambian children with falciparum malaria.

There was a wide variation in the number of BFUe and CFUe in the bone marrow of Gambian children with falciparum malaria and moderate or severe anaemia. However, such children were often not deficient in these erythroid progenitors. The number of BFUe in patients who had parasitaemias greater than 1% was significantly lower than that in patients with parasitaemias less than 1%. There was also a statistically significant negative correlation between the number of BFUe and CFUe in the entire group of children studied. When autologous serum (30%, v/v) was used in the culture system, CFUe growth was observed even in the absence of added erythropoietin (EPO), indicating the presence of high levels of EPO or an EPO-like substance in the anaemic sera. It is concluded that children with Plasmodium falciparum malaria show no major abnormality in their erythroid progenitor cells and that the perturbation of erythropoiesis in such children occurs mainly in the morphologically recognizable erythroid precursor cells. The wide variation observed in the number of CFUe and BFUe in different patients, and the correlations between the number of BFUe and parasitaemia and the number of BFUe and CFUe are all probably largely related to the changing clinicopathological situation in patients with malaria and anaemia.