Angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) occurring within multiple deep lymph nodes and presenting with weight loss and raised CA-125 levels.

We report a case of angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) involving multiple deep mediastinal, abdominal and intramammary lymph nodes in a 52-year-old woman with weight loss and raised CA-125 levels. The unusual clinical presentation with raised CA-125 levels and its occurrence within multiple deep visceral lymph nodes has never been reported in literature.

Autoimmune haemolysis in patients with B-CLL treated with chlorodeoxyadenosine (CDA).

We have treated 19 B-chronic lymphocytic leukaemia (B-CLL) patients with CDA (Leustat, Janssen-Cilag). Four patients developed severe autoimmune haemolytic anaemia, and 2 of these had severe reticulocytopenia due to red cell aplasia/hypoplasia. Two patients died as a complication of the haemolysis one during the primary episode, with a clinical course suggestive of transfusion associated graft-versus-host disease (taGVHD), and one following a relapse of haemolysis. The onset of haemolysis occurs within 4 cycles of CDA therapy and is temporally related to the T-lymphocyte nadir induced by CDA. The presence of a positive DAT prior to therapy in 3 of 4 patients developing haemolysis suggests that the CDA induced T-lymphocytopenia may exacerbate the tendency of certain CLL patients to autoimmune haemolysis.

A comparison of the effect of bcr/abl breakpoint specific phosphothiorate oligodeoxynucleotides on colony formation by bcr/abl positive and negative, CD34 enriched mononuclear cell populations.

In chronic myeloid leukaemia, the expression by clonal cells, of a leukaemia specific bcr/abl chimeric mRNA, makes the condition suitable for the application of "antisense" strategies. Furthermore, the origin of the condition in a pluripotential progenitor allows enrichment of leukaemic clonogenic cells by selection for CD34 expression, together with a useful reduction in contaminating accessory cells. In a methylcellulose clonogenic assay system we incubated bcr/abl expressing (n = 9) and bcr/abl negative (n = 8), CD34 enriched progenitors with phosphothiorate oligodeoxynucleotides (PS oligomers), antisense and sense to the b3a2 and b2a2 chimeric bcr/abl junctional sequences. All samples were cloned in the presence of both antisense, and sense PS oligomers to provide appropriate controls. For bcr/abl positive progenitors, the mean number of colonies formed was reduced by 21 (39%) (P < 0.05) in the presence of the specific antisense oligomer, 11 (20%) (P < 0.05) with the antisense oligomer directed to the alternative junctional breakpoint, and colony formation was not significantly altered by either sense PS oligomer. Colony formation by bcr/abl negative progenitors was not reproducibly reduced by any of the PS oligomers. These results confirm that PS oligomers can have a sequence dependent inhibitory effect on a CD34 enriched progenitor population from patients with chronic myeloid leukaemia.

Macrophage inflammatory protein-1 alpha receptors are present on cells enriched for CD34 expression from patients with chronic myeloid leukemia.

The response of normal and chronic myeloid leukemia (CML), CD34+ cells to human macrophage inflammatory protein-1 alpha (MIP-1 alpha or LD78) was assessed. In tritiated thymidine incorporation assays, stem cell factor plus granulocyte-macrophage colony-stimulating factor stimulated thymidine incorporation in normal CD34+ cells was reduced to 72% of control values in the presence of MIP-1 alpha, whereas incorporation by CML CD34+ cells exposed to the same factors was not altered. In clonogenic assays, the presence of MIP-1 alpha gave a level of colony formation that was 71% of control values for normal progenitor cells, whereas for CML CD34+ cells colony formation was enhanced by 25%. These results suggest that, in vitro, CML progenitor cells are relatively refractory to the growth inhibitory effects of MIP-1 alpha. Using flow cytometry, the specific binding of a biotinylated human MIP-1 alpha/avidin fluorescein (FITC) conjugate to normal and CML mononuclear and CD34+ cell populations was quantified. The data indicate that (for both normal and CML CD34+ cells) there was a single population of cells that express cell surface receptors for MIP-1 alpha and this receptor expression was independent of cell cycle status. CML progenitor cells may be refractory to the effects of MIP-1 alpha as a result of events downstream from receptor expression.

Acute ischaemia of the lower limb: an unusual presenting feature of acute lymphoblastic leukaemia.

Malignant disease is often complicated by coagulation disorders presenting as abnormal clotting or bleeding, acute leukaemia being more often associated with the latter. Acute lymphoblastic leukaemia presenting with peripheral arterial thromboembolism, previously unreported in the literature, is presented. Aetiology, clinical features, and management of coagulation disturbances associated with malignancy are also reviewed.

Serum cytokine levels in patients undergoing bone marrow transplantation.

Daily serum samples collected during 6 autologous and 13 allogeneic BMT were assayed retrospectively for tumour necrosis factor-alpha (TNF), interleukin-6 (IL-6) and C-reactive protein (CRP). In addition, for 6 allogeneic transplant patients soluble TNF receptor (sTNFR) levels were determined. IL-6 levels were regularly raised during febrile episodes and closely mirrored changes in serum CRP but were not predictive for non-infectious major transplant-related complications (TRC). Levels of TNF showed no such close association with infection and in contrast to previously reported data for allogeneic transplants having TRC, TNF levels were consistently detectable in only 3 of 9 patients. Pre-transplant levels were not predictive for the development of TRC and no profile was recognized to be specific for a particular complication. In transplants with only minor complications TNF levels remained consistently undetectable. sTNFR levels increased in a more stable manner in association with TRC, suggesting that they may be a more suitable marker to monitor major TRC.

Acute tumour lysis syndrome.

Acute tumour lysis syndrome results from a rapid massive release of cellular breakdown products consequent upon tumour cell death following effective therapy. This may overwhelm normal excretory mechanisms, resulting in metabolic disturbance which can lead to sudden death or prolonged morbidity from renal impairment.

Heat-induced aggregated human IgG modifies the adherence of human polymorphonuclear cells to cultured endothelium.

The adherence of human blood polymorphonuclear cells (PMNC) to cultured porcine aortic endothelium was enhanced by high concentrations of heat-stable IgG aggregates (HAGG) when sera was omitted from the culture media. With 20% human serum present in the media, HAGG induced a dose-related inhibition of PMNC adhesions with concentrations as low as 10 micrograms/ml producing a significant effect. This inhibitory action of HAGG, which was optimally expressed after 30 min of incubation, seemed to be directed at the PMNC rather than the endothelium. Heat-inactivation of the sera resulted in a marked decline of the inhibitory activity of HAGG. Aggregates of size 15-21 s were demonstrated to be most effective in inhibiting PMNC attachment and it is complexes of this size which are commonly found in the circulation of patients with chronic inflammatory diseases. Immune complex modification of PMNC adherence may control leucocyte extravasation during inflammation.

Adherence of rheumatoid polymorphonuclear cells (PMNs) to cultured endothelial cell monolayers.

Blood polymorphonuclear cells (PMNs) from 40 patients with rheumatoid arthritis (RA) and 40 normal subjects were incubated with confluent cultures of porcine aortic endothelium and their adherence assessed by either a microscopic or radiometric enumeration assay. There was no difference between the number of rheumatoid and control PMNs adhering. The synovial fluid PMNs from patients with RA were less adherent than their paired blood samples when autologous serum was present in the incubation medium and more adherent when serum was absent. Most of the RA sera tested inhibited the adhesion of normal PMNs, an effect that was not due to an increase in PMN aggregation. A similar inhibition was seen with sera obtained from patients with Felty's syndrome. These findings suggest that there is no intrinsic difference between the adhesiveness of rheumatoid PMNs and normal PMNs but that there are soluble factors present in RA serum which inhibit the attachment of normal PMNs to vascular endothelium.

Rheumatoid blood decreases the adherence of polymorphonuclear cells (PMNs) to cultured endothelium.

Rheumatoid sera and plasma inhibited the adherence of normal blood polymorphonuclear cells (PMNs) to cultured porcine endothelium. This inhibition of adhesion was not seen when PMNs were treated with the plasma or serum from normal subjects or patients with other inflammatory arthropathies. The abrogation of PMN adherence was directly related to the levels of circulating immune complexes and was not dependent upon the type of anti-inflammatory therapy that the patients were receiving nor on any of the recorded clinical parameters. A similar inhibition of adhesion was seen with heat induced aggregated human IgG (HAGG) provided that serum was present in the culture medium. In view of these results we propose that circulating immune complexes in RA may have a significant role in controlling the interaction of PMNs with vascular endothelium and in perpetuating the entry of these cells into the synovial fluid of the inflamed joints.