MRONJ risk reduction pathway - 360 degree survey.

Introduction Bisphosphonates and denosumab reduce the risk of skeletal events in some malignancies (for example, breast, myeloma). These drugs carry a significant risk of a difficult-to-manage side effect of medication related osteonecrosis of the jaw (MRONJ). Preventive dental screening and treatment reduces the incidence of MRONJ. A managed clinical network (MCN) has been used to provide a MRONJ risk reduction pathway. A 360 degree survey was undertaken to assess the effectiveness of the pathway.Aim The aim of the 360 degree survey was to evaluate if this preventive pathway fulfilled its aims based on patient and stakeholder responses.Method A multidisciplinary, cross-service, cross-health board MRONJ preventive pathway has been developed. A 360 degree feedback survey of patients and other stakeholders was undertaken.Results Overall, this survey revealed high levels of satisfaction across patients, oncologists, community dental services, general dental services, and hospital managers.Conclusion Alternative ways of delivering MRONJ preventive pathways can be developed and assessed using iterative stakeholder feedback aided by a robust clinical governance framework.

Postinfection purpura fulminans in a patient heterozygous for prothrombin G20210A and acquired protein S resistance.

Purpura fulminans usually consists of large, often symmetrical, spreading ecchymosis, which may later develop into extensive areas of skin necrosis and peripheral gangrene. Postinfectious purpura fulminans associated with an autoantibody directed against protein S has been described. The interaction and the contribution of recently described mutations such as factor V Leiden and prothrombin G20210A to the development and progression of postinfectious purpura fulminans and venous thrombosis is not known. The authors describe a patient heterozygous for prothrombin G20210A who developed purpura fulminans and extensive venous thrombosis secondary to acquired protein S deficiency.

Leukemia-associated changes identified by quantitative flow cytometry. III. B-cell gating in CD37/kappa/lambda clonality test.

Normal and malignant B-lymphoid cells were studied for CD37 antigen expression with three-color immunofluorescence (IF) in combination with kappa/lambda light chain staining, and by quantitative immunofluorescence utilizing the QIFI test. Peripheral B cells brightly expressed CD37 antigen (median 80-114 x 10(3) molecules/cell). Moderate to high levels (> 20 x 10(3)/cell) of CD37 expression were detected in 364 in 366 cases of peripheral B-cell disorders including all cases of B-ALL, B-cell lymphomas and B-CLL as well as eight of ten cases of PLL. By contrast, slg- B-cell precursors and other cell types in normal bone marrow (BM) were CD37-/CD37dull (< 10 x 10(3) molecules/cell). The negativity for CD37 or only CD37dull expression was confirmed in 180 of 182 cases of precursor B-ALL and 196 cases of non-B malignancies. Among the CD37 cluster, the RFB7 antibody of IgM class showed the weakest binding to non-B cells. In 64 normal samples of blood and BM the CD37+ gated cells showed normal kappa/lambda ratios as expected, while in 100 cases of B malignancy striking changes such as kappa/lambda monoclonality (79%) and aberrant slg- or sigdull expression (21%) were seen among the gated CD37+ B cells. The CD37/kappa/lambda test identified as few as 0.5% kappa+ or lambda- monoclonal B cells admixed to normal BM: circulating B-lymphoma cells were seen in nine patients with morphologically normal blood count. The discrimination of the Kolmogorov-Smirnov (KS) test for kappa/lambda excess was also improved by CD37+ B gating. Thus CD37+ B-cell gating and kappa/lambda analysis is a simple and sensitive routine test, e.g. when combined with autogating on a Cytoron-Absolute cytometer, for identifying malignant B cells in minimally involved BM and blood.

Combination chemotherapy including epirubicin for the management of non-Hodgkin's lymphoma.

One hundred patients with untreated non-Hodgkin's lymphoma were entered in a prospective randomized study in South and West Wales designed to assess the value of the anthracycline antibiotic, epirubicin (4'-epidoxorubicin), in their management. Patients with low grade histology and progressive disease were randomized to receive either epirubicin, vincristine and prednisolone (EVP) or cyclophosphamide, vincristine and prednisolone (CVP). The response rate of 81% in patients receiving EVP with complete remission rate of 52% were similar to a response rate of 88% and complete remission rate of 58% for patients receiving CVP. No difference was observed in survival between the two groups. Patients with high grade lymphoma were randomized to receive either cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or cyclophosphamide, epirubicin, vincristine and prednisolone (CEOP). The response rate was 71% for CHOP and 84% for CEOP. The complete remission rates were 46% for CHOP and 61% for CEOP. The cardiotoxicity of the two anthracyclines were monitored closely in 45 patients using measurements of systolic time intervals. Patients receiving epirubicin tolerated higher dose per course and higher total cumulative dose with less evidence of compromised left ventricular function than patients receiving doxorubicin. Epirubicin is an effective agent when used in combination chemotherapy in both low grade and high grade lymphoma with less toxicity than doxorubicin.

Erythropoiesis and iron metabolism in Hodgkin's disease.

Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.

Systolic time interval as index of schedule--dependent doxorubicin cardiotoxicity in patients with acute myelogenous leukaemia.

The ratio of the pre-ejection period to the left ventricular ejection time (PEP:LVET) was measured in two groups of patients with acute myeloblastic leukaemia (AML) receiving the anthracycline antibiotic doxorubicin (DXR). Patients receiving high doses of DXR per course (about 90 mg/m2) showed a significant increase in the PEP:LVET ratio irrespective of the total cumulative dose. At a lower dose per course (less than 50mg/m2) only patients who had a total cumulative dose of over 450 mg/m2 showed significant increases in ratio. ECG changes were seen in both groups of patients but did not correlate significantly with the dosage. These findings, which suggest that DXR cardiotoxicity is schedule dependent, are important in the design of schedules of DXR for treating cancer and in interpreting the changes in systolic time intervals (STIs) observed with different schedules. Measurement of the STI is a simple and convenient method of assessing DXR cardiotoxicity. While a total DXR dose of 550 mg/m2 should not normally be exceeded, by carefully monitoring the STI the recommended total dose may be exceeded safely in selected patients.

Factor VIII inhibitor and bronchogenic carcinoma.

An inhibitor to procoagulant factor VIII (FVIIIC) developed in a patient three years after palliative resection of a bronchogenic carcinoma. The inhibitor was not active against ristocetin cofactor but possibly had some activity against factor XI. It responded to immunosuppressive therapy. This is apparently the first reported association of carcinoma and factor VIII inhibitor.

An assessment of laparotomy in the management of patients with Hodgkin's disease.

Planned laparotomy and splenectomy has been a safe investigation for sixty patients with clinical Stage I, II or III Hodgkin's disease. Twenty-four of the 60 patients (40%) changed stage and 18 patients had their treatment altered as a consequence of the procedure. Forty-three per cent of patients without a palpably enlarged spleen had unsuspected disease when the organ was examined pathologically, although a false positive spleen was uncommon. Eight of 55 patients (14.5%) had intra-abdominal disease which was not detected by lymphangiography. Intra-abdominal disease occurred with all histological sub-types and was found in two patients who had clinical Stage I disease and lymphocyte predominance in their node histology. Sarcoid-like granulomata were found in ten patients, seven in the spleen, one in the liver and spleen, one in the skin and one in the original node biopsy. In the majority of patients, granulomata were associated with nodular sclerosing or mixed cellular histology. In all ten patients the Hodgkin's disease was suppressed by appropriate chemotherapy and disease has not recurred. No patient has shown any clinical evidence of sarcoidosis and the Kveim test done in three patients was negative. Our experience encourages us to recommend staging laparotomy for all adult patients with Hodgkin's disease which does not show obvious generalized spread beyond lymph nodes.