Plasma matrix metalloprotease 9 correlates with blood lymphocytosis, leukemic cell invasiveness, and prognosis in B-cell chronic lymphocytic leukemia.

The complex biology underlying chronic lymphocytic leukemia cell migration and tissue invasiveness is not yet completely understood and might provide novel predictive markers and therapeutic targets. A total of 36 patients out of treatment from at least 3 months were enrolled and followed up for a median period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue inhibitor of metalloproteases 1 plasma levels and production/release from lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay (ELISA) analysis. Malignant and normal lymphocyte mobility and matrix-degradation capability were studied using a Boyden chamber system, with and without autologous plasma. Free matrix metalloprotease 9 plasma levels were related with blood lymphocytosis, especially in more advanced stages (p = 0.003), and higher concentrations were associated with an increased disease progression risk (hazard ratio = 9.0, 95% confidence interval = 1.5-13.8). Leukemic cells expressed and secreted very little matrix metalloprotease 9. On the contrary, normal lymphocytes derived from the same leukemic patients showed matrix metalloprotease 9 intracellular levels that were lower in subjects with higher blood lymphocytosis (p = 0.024) and more advanced stages (p = 0.03); the released quantities were inversely associated with matrix metalloprotease 9 plasma concentrations (p = 0.035). Leukemic cells had a reduced spontaneous mobility and matrix-degradation capability that were stimulated by autologous plasma (p = 0.001) and normal lymphocytes (p = 0.005), respectively. Matrix metalloprotease 9 affected cell invasiveness depending on concentration and disease stage. In conclusion, chronic lymphocytic leukemia cells have a reduced mobility, matrix-degradation capability, and matrix metalloprotease 9 production compared to their own autologous normal lymphocytes. They are exposed to matrix metalloprotease 9 of prevalently systemic origin whose higher levels are associated with both leukemic and normal lymphocyte accumulation in the peripheral blood and have a negative prognostic value.

Consolidation treatment with rituximab induces complete and persistent remission of mixed type Evans syndrome.

We describe a 58-year-old woman affected by immune thrombocytopenic purpura (ITP) since 1999, well controlled by low doses of steroid for 4 years, who experienced a relapse with severe mixed type Evans syndrome in March 2006. After an initial response to high doses of steroid, severe anaemia recurred 2 months later, this time resistant to second-line therapy with intravenous immunoglobulins (IVIG) and cyclophosphamide. So in May, we started the treatment with anti-CD20 monoclonal antibody rituximab with the dose of 375 mg/m2 once weekly for a total of four doses. We obtained a full normalization of haemoglobin concentration, but the disease haemolytic parameters persisted. Therefore, we decided to treat the patient with two monthly courses of rituximab, and a gradual normalization of haptoglobin and lactate dehydrogenase (LDH) plasma levels was finally achieved, with a sustained response up to date, lasting more than 12 months. We conclude that rituximab treatment is effective in refractory patients with mixed type Evans syndrome, and consolidation therapy should be considered to prolong beneficial effects achieved during the induction.

The prognostic value of 18F-FDG PET-CT in the management of Hodgkin's lymphoma: preliminary results of a prospective study.

BACKGROUND: To date, Hodgkin's lymphoma (HL) patients have achieved long-term survival of more than 80%. Unfortunately, longer follow-up has shown serious adverse effects of the treatments used. For this reason, therapeutic strategies are becoming more tailored to the individual patient s prognosis. Pre-treatment risk factors for early-stage and advanced-stage HL are well known indicators of prognosis. Recently, early interim (18)F-FDG PET has been shown as a strong and independent predictor of progression-free survival in HL. Our aim was to assess response to therapy by repeating (18)F-FDG-PET/CT after four and six chemotherapy cycles. MATERIAL AND METHODS: We evaluated 21 consecutive patients affected by (HL) and presenting for assessment over a period of three years. All patients underwent initial staging with (18)F-FDG-PET/CT along with standard staging procedures. We tailored an individual treatment plan dependent on pre-treatment risk factors and initial (18)F-FDG-PET/CT. With the aim of the best definition of response to treatment, we repeated (18)F-FDG-PET/CT after two (FDG-PET 2), four (FDG-PET 4) and six (FDG-PET 6) chemotherapy cycles. Chemotherapy was typically given for four cycles in early disease stages and was prolonged to six to eight cycles in advanced disease stages, depending on PET findings. RESULTS: Our results showed a strong negative predictive value in detecting responders in early stage HL and a positive predictive value in advanced-stage patients. Clinical stage, extra-nodal sites and the positivity of the (18)F-FDG-PET/CT performed during chemotherapy were also noted as strong determinants of response to treatment. Moreover, in our series the (18)F-FDG-PET/CT data obtained after only two chemotherapy cycles (FDG-PET 2) were the same of those obtained after FDG-PET 4 and FDG-PET 6 controls. CONCLUSION: The preliminary data of the present study confirm those of previous published studies about the negative predictive value of (18)F-FDG-PET/CT performed after four and six chemotherapy cycles, which contributed to the decision to stop treatment and to avoid radiotherapy in HL patients. Nonetheless, our preliminary data seems to suggest that only the (18)F-FDG-PET/CT performed after two cycles of chemotherapy (FDG-PET 2) is able to provide the same prognostic information of the FDG-PET 4 and FDG-PET 6 earlier.

Epstein-Barr Virus-Positive Mucocutaneous Ulcer Mimicking Rectal Carcinoma at 18F-FDG PET/CT.

We report focally intense F-FDG PET/CT rectal activity (SUVmax = 25) with a horseshoe distribution in an 81-year-old man with B-cell chronic lymphocytic leukemia and suspected Richter transformation. While imaging findings were typical for rectal adenocarcinoma, histology revealed Epstein-Barr virus-positive mucocutaneous ulcer.

[Central venous catheter-related right atrial thrombosis in a patient with Hodgkin's lymphoma]. / Trombosi atriale destra correlata a catetere venoso centrale in un paziente con linfoma di Hodgkin.

Central venous catheters (CVC) are commonly used in clinical practice. Although long-term complications are uncommon, catheter-related right atrial thrombosis is a rare but potentially life-threatening one. The optimal management is still controversial. We report the case of a young woman affected by Hodgkin lymphoma with CVC-related right atrial thrombosis diagnosed during routine echocardiography. After initial anticoagulation treatment, she complicated with pulmonary embolism, and the mass was surgically removed via a minimally invasive approach with right minithoracotomy access. Surgery was well tolerated, without complications and with prompt recovery. This case confirms how CVC can lead to thrombosis in the right atrium and how this complication can rapidly deteriorate. Moreover, the possible treatment options for the successful management of this complication are discussed, along with the available literature, showing the advantages of a minimally invasive approach.

Response criteria for malignant lymphoma.

In the last 35 years, many attempts have been made to define criteria for the assessment of treatment response in malignant lymphoma. These systems, with respect to both morphological and molecular imaging, aim to standardize scan results, in order to simplify the interpretation of findings, facilitate multicentric research trials, and compare published data. Unfortunately, there is no consensus among the main international hematological associations on which criteria are the most appropriate. This detailed and comprehensive description of all classifications intends to focus attention on this topic.