An acquired Bernard-Soulier-like platelet defect associated with juvenile myelodysplastic syndrome

Bernard-Soulier syndrome is an inherited bleeding abnormality characterized by thrombocytopenia with large platelets and deficiency of the platelet membrane glycoprotein (GP) Ib-IX complex. We have identified a young female with an acquired Bernard-Soulier-like platelet defect and a coexisting primary myelodysplastic disorder. Abnormal bruising had developed at age 5. A normal platelet count with some giant platelets was noted at age 7. At age 9 she developed a large haematoma following surgery. Laboratory investigation revealed thrombocytopenia and large platelets. Platelet membrane glycoprotein analysis showed a marked deficiency of the components of the GP Ib-IX complex (approximately equal to 25% of normal). Flow cytometry revealed two populations of platelets: a predominant population of large platelets lacking the GP Ib-IX complex and a minor population of normal-sized platelets with normal GP Ib-IX expression. The patient developed progressive anaemia, more severe thrombocytopenia and neutropenia, and circulating blast cells were seen. A bone marrow showed gross hypercellularity with marked dysplasia of all three lineages and increased blasts. Marrow cytogenetic studies showed the presence of monosomy 7 in all metaphases, with an additional trisomy 21 in 10%. Peripheral blood cells were normal 46XX. The above data are consistent with an acquired myelodysplastic syndrome associated with a Bernard-Soulier-like platelet defect.     

CXCR4 antagonists mobilize childhood acute lymphoblastic leukemia cells into the peripheral blood and inhibit engraftment.

The role of CXCL12 in the bone marrow (BM) homing and growth of B-cell progenitor acute lymphoblastic leukemia (ALL) has been established. However, the effect of modulating CXCL12/CXCR4 interactions on the retention of ALL cells within the supportive BM microenvironment and the expansion and dissemination of ALL cells in vivo has not been examined. We used mouse models of human childhood and murine leukemia and specific peptide and small molecule CXCR4 antagonists to examine the importance of CXCL12/CXCR4 in the development of leukemia in vivo. CXCR4 antagonists mobilized ALL cells into the peripheral blood (PB). Extended administration of CXCR4 antagonists to mice with leukemia resulted in a reduction in the number of leukemic cells in the PB and spleens of animals compared to control treated animals in three of the five cases tested. There was also a marked reduction in the dissemination of ALL cells to extramedullary sites including liver and kidney in all cases where this occurred. Considering the inhibitory effect of stromal layers on the activity of chemotherapeutic agents and the interactive effect of CXCL12 antagonists with chemotherapeutic agents in vitro, this raises the possibility of using these agents to potentiate the effects of current chemotherapy regimens.     

Vascular air embolism: A rare complication of nasal CPAP

Abstract: A preterm infant developed bilateral tension pneumothoraces and extensive vascular air embolism 6 h after being commenced on nasal continuous positive airway pressure (CPAP). Neonatal clinicians should be aware that catastrophic vascular air embolism could occur in infants receiving nasal CPAP, a modality of respiratory support conventionally considered non-invasive and 'safe'.     

Dental caries risk indicators among Australian Aboriginal young adults

Jamieson LM, Roberts‐Thomson KF, Sayers SM. Dental caries risk indicators among Australian Aboriginal young adults. Community Dent Oral Epidemiol 2010; 38: 213–221. © 2009 John Wiley & Sons A/S Abstract – Objectives: To determine dental caries risk indicators among a birth cohort of Australian Aboriginal young adults (n = 442). Methods: Data were from the Aboriginal Birth Cohort study, a prospective longitudinal investigation of Aboriginal individuals born 1987–1990 at an Australian regional hospital. Models representing demographic, socioeconomic, behavioural, dental service utilization and clinical oral health variables were tested using multivariate regression. Results: The percent DT > 0 was 72.9 (95% CI 68.7–77.1), mean DT was 4.19 (95% CI 3.8–4.6), percent DMFT > 0 was 77.4 (95% CI 73.5–81.3) and mean DMFT was 4.84 (95% CI 4.4–5.3). After controlling for other covariates, risk indicators for percent DT > 0 included soft drink consumption every day or a few times a week (PR 1.25, 95% CI 1.08–1.45), not consuming milk every day or a few times a week (PR 1.16, 95% CI 1.04–1.30) and sweet consumption every day or a few times a week (PR 1.18, 95% CI 1.04–1.33). Risk indicators for mean DT included sweet consumption every day or a few times a week (B = 1.14, 95% CI 0.27–2.02), nonownership of a toothbrush (B = 0.91, 95% CI 0.10–1.87) and presence of plaque (B = 2.46, 95% CI 0.96–3.96). Those with 4 + occupants in their house the previous night had 1.2 times the prevalence of having DMFT > 0 than their counterparts with less household occupants (95% CI 1.01–1.49). Percent DMFT > 0 was also associated with consumption of soft drink every day or a few times a week (PR 1.18, 95% CI 1.04–1.34) and consumption of sweets every day or a few times a week (PR 1.23, 95% CI 1.10–1.37). Mean DMFT was higher among those who consumed sweets every day or a few times a week (B = 0.13, 95% CI 0.05–0.22) and who had dental anxiety (B = 0.10, 95% CI 0.01–0.19). Conclusions: In an Australian Aboriginal young adult cohort, risk indicators for dental caries included social determinants such as household size, dietary behaviours such as regular consumption of soft drink and sweets, dental behaviour such as nonownership of a toothbrush and dental anxiety.     

Endothelial cells and normal circulating haemopoietic cells share a number of surface antigens

Human endothelial cells, cultured from umbilical cord veins, have been evaluated for expression of a large number of cell surface antigens with known haemopoietic, particularly myeloid, cell distribution. This was achieved by evaluating endothelial reactivity (using non-fixed cells) with groups of monoclonal antibodies (MAB) belonging to distinct Clusters of Differentiation (CD), as defined by the Third International Workshop on Leukocyte Differentiation Antigens (ILWS). Results indicate that many antigens known to be present on haemopoietic cells, including those on platelets, are co-expressed on endothelial cells. The most intense degree of reactivity was seen using MAB to CD-9 and CD-13, although significant reactivity was also observed using MAB to CD-31 and CD-32. Data also suggests weak binding to endothelial cells of MAB belonging to CD-14, CD-15 and CD-16. A number of unclustered MAB reactive with haemopoietic antigens can also be shown to bind to endothelial cells.     

GM-CSF after allogeneic bone marrow transplantation: accelerated recovery of neutrophils,monocytes and lymphocytes*

Abstract Ten patients given HLA-identical sibling marrow transplants for lymphoid malignancy received recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) from day 7 to day 13 inclusive post transplant. Patients were prepared for transplantation with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. Immunosuppression to minimise the risk of graft-versus-host disease (GVHD) was cyclosporin/short methotrexate. Results were compared with a historical control group of patients (n = 16) given matched sibling transplants for acute leukaemia and receiving the same immune suppressive regime but not given GM-CSF. Recovery of total white cells, neutrophils, monocytes and lymphocytes was more rapid in the GM-CSF recipients (p< 0.02). There was a suggestion of a decrease in non-viral infections in the first 30 days in the GM-CSF recipients (p = 0.09). There was, however, no significant difference in the severity of oropharyngeal mucositis nor in the duration of the transplant hospitalisation. Surprisingly, the severity of acute GVHD was higher in the GM-CSF recipients with six of eight evaluable patients having grade II-IV acute GVHD (p = 0.003). Two GM-CSF recipients developed a fluid retention/capillary leak syndrome. These findings indicate a need for caution in the use of GM-CSF after allogeneic marrow transplantation.     

Unusual immunophenotypes in acute leukaemias: incidence and clinical correlations

The incidence and clinical implications of unusual patterns of expression of leucocyte differentiation antigens in acute leukaemia were assessed on 568 newly diagnosed paediatric and adult cases undergoing immunophenotyping with a panel of monoclonal antibodies at a single centre. Among patients with the precursor B (common) form of acute lymphoblastic leukaemia (ALL), the major variant seen was the group of 15 cases with expression of myeloid surface antigens. 4.5% of ALL cases tested with antibody to CD-11b were positive, 5.1% were CD-13+, and 10.8% CD-33+. All 15 patients achieved a complete remission with chemotherapy, with six of eight children and four of seven adults remaining disease free. A smaller proportion (1.5%) of precursor B ALL patients showed expression of the T lineage marker, CD-7. The only significant variant seen in the precursor T-ALL group was expression of HLA-DR antigen, which was found in five of 35 cases; although all responded to treatment, only one remains a disease-free survivor. Among patients with acute myeloid leukaemia (AML), expression of the lymphoid markers terminal transferase (TdT) and CD-7 were commonly seen (22.2% and 28.4% respectively of cases tested). Other lymphoid markers detected on AML cases were CD2 (11.1%), CD-10 (1%) and CD-19 (4.4%). These results confirm that examples of lineage infidelity are regularly seen in large series of patients with acute leukaemia. Prospective studies using uniform treatment protocols are required to establish whether these patients have significantly different disease outcomes.