Herpes simplex virus type-I and pyogenic granuloma: a vascular endothelial growth factor-mediated association?

Pyogenic granuloma (PG) is a vascular endothelial growth factor (VEGF)-related neoangiogenic process. Minor trauma, chronic irritation, certain drugs and pregnancy may favor PG. Viral triggers have not been reported up to date. A 52-year-old woman with hairy-cell leukemia presented because of a 3-month history of a giant pseudotumoral lesion on her left cheek. All prior antibacterial, antifungal and anti-inflammatory treatments had failed. Histology revealed PG with sparse and isolated epithelial cell aggregates. Immunohistochemistry (IHC) identified herpes simplex virus type-I (HSV-I) antigens in the nuclei and cytoplasm of normal-appearing as well as cytopathic epithelial cells, suggesting a chronic, low-productive HSV infection. No HSV-I signal was evidenced in the endothelial cells of the PG. Furthermore, IHC revealed VEGF in the HSV-I infected epithelial cells as well as within the PG endothelial cells. These results incited oral treatment with valaciclovir, and the PG promptly resolved after 2 weeks. These findings suggest that a chronic HSV-I infection might play an indirect, partial role in neoangiogenesis, presumably via HSV-I infection-related stimulation of keratinocytic VEGF production.

[Diffuse large B cell lymphoma: management in 2012]. / Prise en charge du lymphome B diffus à grandes cellules en 2012.

Diffuse Large B Cells Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and comprises a large number of different entities with different clinico-pathological characteristics. The role of positron emission tomography is essential during the initial staging and post treatment assessment, and potentially at early- or mid-treatment evaluation of response. First line therapy comprises immuno-chemotherapy with rituximab and different cytotoxic agents that differ for components, dosages and frequency of administration taking worldwide-recognized pre-treatment prognostic variables into account. After relapse, peripheral blood stem cells transplantation remains the only chance of cure. This review attempts to summarize the current state of our knowledge by highlighting the leads pursued to further improve current therapeutic results.

[Mantle cell lymphoma]. / Le lymphome du manteau.

Mantle cell lymphoma comprises 3 to 10% of non-Hodgkin's lymphomas. Cyclin D1 expression due to t(11 ;14) (q13 ;32) is considered as a hallmark of this lymphoma and plays a pivotal role in the pathophysiology of lymphoma transformation. Median age at diagnosis ranges from 60 to 70 years, and diagnosis is often made at an advanced stage with widespread lymphadenopathy and extranodular (particularly bone marrow and gastrointestinal) infiltration. First line treatment consists of combination chemotherapy followed with autologous hematopoietic cell transplantation (HCT) in younger patients, while allogeneic HCT following non-myeloablative conditioning might have a role in patients relapsing after autologous HCT.

[How I treat... Acute myeloid leukemia in older patients with good performance status]. / Comment je traite...La leucémie myéloblastique aiguë (LMA) du sujet âgé en bon état général.

This article describes the treatment of acute myeloid leukemia in older patients with good performance status, and then discusses briefly some future therapeutic perspectives.

Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease.

BACKGROUND: Relapse after treatment of Hodgkin's disease (HD) is usually identified as a result of the investigation of symptoms. We undertook this study to examine the value of whole-body positron emission tomography (PET) for the detection of preclinical relapse. PATIENTS AND METHODS: Thirty-six patients underwent 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)F-FDG) PET at the end of treatment and than every 4-6 months for 2-3 years after the end of polychemotherapy and/or radiotherapy. In those cases of abnormal (18)F-FDG accumulation a confirmatory study was performed 4-6 weeks later. RESULTS: One patient had residual tumor and four patients relapsed during a follow-up of 5-24 months. All five events were correctly identified early by (18)F-FDG PET. Residual tumor or relapse was never first diagnosed based on clinical examination, laboratory findings or computed tomography (CT) studies. Two patients presented B symptoms and the three others were asymptomatic at the time of residual disease or relapse. Confirmation of residual disease or relapse was obtained by biopsy in four patients 1, 1, 5 and 9 months after PET and by unequivocal clinical symptoms and CT studies in one patient 3 months after PET. False-positive (18)F-FDG PET studies incorrectly suggested possible relapse in six other patients, but the confirmatory PET was always negative. Our study also provides important information about physiological (18)F-FDG uptake in the thymus. CONCLUSIONS: Our data suggest the potential of (18)F-FDG PET to detect preclinical relapse in patients with HD. This could help identify patients requiring salvage chemotherapy at the time of minimal disease rather than at the time of clinically overt relapse. Further studies are warranted to determine the impact of PET on treatment management and outcome. In fact, the aim of follow-up procedures is not only to detect preclinical relapse but mainly to obtain better results by starting salvage treatment earlier. A cost-benefit analysis will also be necessary before (18)F-FDG PET can be used routinely in the follow-up of patients with HD.

[End of treatment evaluation in patients with aggressive non-Hodgkin's lymphoma]. / Comment établir le bilan de fin de traitement des patients atteints de lymphomes non-hodgkiniens (LNH) de malignité intermédiaire ou élevée?

Incomplete regression of a lymphomatous mass after chemotherapy and/or radiotherapy constitutes a major problem in the treatment of lymphoma. In patients with persisting tumor, it could be reasonable to use salvage therapy and possibly hematopoietic stem cell transplantation at the time of minimal disease rather than at the time of clinically overt relapse. The authors reviewed the most appropriate imaging techniques for the assessment of response to treatment. The limitations of CT and MRI for predicting the nature of residual masses are well known. 67Ga scintigraphy has become a standard procedure for the posttreatment evaluation of patients with lymphoma, but it appears that 18F-FDG PET may be a more effective method. Personal experience in the field of PET scan is reported. Although PET should be considered the noninvasive imaging modality of choice, a histological confirmation of residual disease is always necessary before starting salvage therapy. 18F-fluorodeoxyglucose is not a tumor specific radiotracer.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL).

BACKGROUND: Although PET has been shown to be highly sensitive in the primary staging of lymphoma, previous studies with small numbers of patients indicated that low-grade NHL may not always be adequately detected by PET. We undertook this study to determine factors influencing the detection of lesions by PET in low-grade NHL and to evaluate the utility of PET in this indication. PATIENTS AND METHODS: Forty-two patients underwent conventional staging procedures (clinical examination, oto-rhino-laryngologic examination, computed tomography of the chest, abdomen and pelvis, gastroscopy and bone marrow biopsy as well as whole-body non-attenuation corrected 18F-FDG-PET RESULTS: PET detected 40% more abnormal lymph node areas than conventional staging in follicular lymphoma but was inappropriate for the staging of small lymphocytic lymphoma where it detected less than 58% of abnormal lymph node areas. PET showed more lesions than conventional staging for peripheral (34% more lymph node areas detected) and thoracic lymph node (39% more) areas but not for abdominal or pelvic lymph nodes (26% fewer areas detected). The sensitivity to detect bone marrow infiltration was unacceptably low for PET. In contrast, PET was as effective as standard procedures for the detection of other extranodal localizations, although a few localizations were detected only by PET and a few others only by conventional procedures. CONCLUSIONS: PET may contribute to the management of patients with low-grade follicular NHL. For the other low-grade lymphoma subtypes, the role of PET is less evident. Further studies using PET to evaluate the results of treatment or to diagnose disease recurrence are warranted in low-grade follicular NHL.

Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease.

BACKGROUND AND OBJECTIVES: Accurate staging is essential in order to determine appropriate treatment in Hodgkin's disease (HD). (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) offers the advantage of metabolic imaging that is largely independent of morphologic criteria. In the present study we evaluated the role of (18)F-FDG PET compared to routine procedures for the staging of patients with HD. DESIGN AND METHODS: Thirty-three patients with HD underwent standard staging procedures (clinical examination, laboratory screening, chest X-ray, computed tomography (CT) of the chest and abdomen and bilateral bone marrow biopsies) and a whole-body (18)F-FDG PET study. In clinical examination, an isolated lymph node > 1 cm or multiple lymph nodes > or = 1 cm in size were considered abnormal. Positive findings at both clinical examination or CT and (18)F-FDG PET were regarded as actual locations of disease. Negative findings with both methods were regarded as true negative (no involvement by HD). In cases of discrepancy, response to treatment and follow-up data were used to assess the overall accuracy of the patient's original evaluation. RESULTS: Completely concordant results in lymph node staging were observed in 20 patients. The two staging procedures indicated complementary information in 1 patient. Conventional staging indicated more pathologic lymph node areas in 6 patients (at least 1 false positive). (18)F-FDG PET showed more sites in 6 patients. The sensitivity of (18)F-FDG PET in detecting all known pathologic lymph nodes was 83% for peripheral lymph nodes, 91% for thoracic lymph nodes and 75% for abdominal and pelvic lymph nodes. Conventional staging procedures and (18)F-FDG PET indicated the same tumor stage in 26 patients. Based on (18)F-FDG PET, downstaging was suggested in 4 patients, including a biopsy-proven case. However in 1 of these cases this was incorrect. (18)F-FDG PET suggested upstaging in 3 patients. Based on conventional staging or (18)F-FDG PET the same treatment strategy was defined in 32 patients. In one patient (18)F-FDG PET downstaged disease extension (stage IIIA-->IIA) that would have suggested radiotherapy as a possible treatment option. INTERPRETATION AND CONCLUSIONS: (18)F-FDG PET provides an easy and efficient whole-body method for the evaluation of patients with HD. (18)F-FDG PET never missed tumor masses >1 cm. (18)F-FDG PET detected additional sites of disease not seen by conventional procedures and identified absence of disease in some sites suspected to be involved. However, in our patients this did not translate into changes in treatment strategy.

[The Hemovigilance Commission of the University Hospital Center]. / La commission d'hémovigilance du CHU.

As suggested by the National Blood Council, a Hemovigilance Committee was set up in the University Hospital of Liège in 1995. A multidisciplinary discussion takes place on any action aiming at the improvement of transfusion safety, and the follow-up of its implementation. The first issue to be discussed was the set up of a detailed documentation of all blood transfusions. The data are now recorded on a single document allowing proper identification of people and products involved, and of the eventual incidents. This document has lead to a better transfusion safety and to an improved administrative management of blood transfusion. The Commission has been coordinating two multi-centric studies analyzing the consumption of fresh blood products and the incidence of transfusion reactions. Among blood-saving policies, autologous transfusion and volume reduction of samples drawn for laboratory purposes have been discussed. Other measures were taken to improve the labeling of samples for cross-mach and to actively follow-up transfusion reactions. By its actions and advises, the Commission aims to direct strategies towards a safe and rational use of blood products.

Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve clinical outcome. Therefore, we studied the value of (18)F-FDG PET for early evaluation of response in patients with non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: We studied 28 patients by (18)F-FDG PET after a median of 3 cycles of polychemotherapy. The presence or absence of abnormal (18)F-FDG uptake was correlated to clinical outcome (median follow-up: 17.5 months, range 4-47 months). RESULTS: Five of 28 patients still had increased (18)F-FDG uptake in one or more sites previously shown to be involved by lymphoma at baseline evaluation. Only one of these five patients entered complete remission (CR), whereas among the 23 patients with negative (18)F-FDG PET studies, two died of toxicity during chemotherapy and all the others entered clinical CR (p<0.00001). All five patients with and 7/21 patients without residual abnormal (18)F-FDG uptake relapsed or reprogressed (positive predictive value for relapse: 100%, negative predictive value: 67%). By Kaplan-Meier analysis, progression-free survival (PFS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive patients and 81+/-9% and 62+/-12% for (18)F-FDG PET negative patients (p=0.0001). Overall survival (OS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive and 87+/-7% and 68+/-11% for (18)F-FDG PET negative patients (p<0.0001). INTERPRETATION AND CONCLUSIONS: Persistent tumoral (18)F-FDG uptake after a few cycles of polychemotherapy is predictive of CR, PFS and OS in NHL. Further studies are warranted to determine whether (18)F-FDG PET has a predictive value independent from conventional prognostic factors. However, the sensitivity of qualitative (18)F-FDG PET imaging in identifying patients with a poor outcome was insufficient. Earlier evaluation after only one cycle of chemotherapy and quantitative analysis might increase the sensitivity of 18F-FDG PET is predicting treatment failure.

Successful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF.

BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials.

Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging.

A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) offers the advantage of functional tissue characterization that is largely independent of morphologic criteria. We compared 18F-FDG PET to computed tomography (CT) in the posttreatment evaluation of 54 patients with Hodgkin's disease (HD) or intermediate/high-grade non-Hodgkin's lymphoma (NHL). Residual masses on CT were observed in 13 of 19 patients with HD and 11 of 35 patients with NHL. Five of 24 patients with residual masses on CT versus 1 of 30 patients without residual masses presented a positive 18F-FDG PET study. Relapse occurred in all 6 patients (100%) with a positive 18F-FDG PET, 5 of 19 patients (26%) with residual masses on CT but negative 18F-FDG PET, and 3 of 29 patients (10%) with negative CT scan and 18F-FDG PET studies (P

Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis.

Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis.

Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.

BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and CD34+ cell count were performed on peripheral blood and leukaphereses products. After log transformation of the data, differences between groups were assessed with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and two patients required 2 and 3 mobilization cycles respectively to reach our target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically increased when G-CSF was added to CT for mobilization. In collections primed with CT and G-CSF, better yields were obtained in patients with breast cancer or small-cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among potential predictive factors of CT- and G-CSF-primed harvests, we found that the CD34+ cell count in peripheral blood (PB) was strongly correlated with both the CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6) CD34+ cells/kg were harvested when the CD34+ cell count in blood was above 20x10(6)/L. Similarly, better results were obtained in collections performed when the percentage of myeloid progenitors in blood on the day of apheresis was above 5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+ cells/L in PB were associated with higher yields of PBPC in collections mobilized with CT+G-CSF.

Whole-body 18F-FDG PET for the evaluation of patients with Hodgkin's disease and non-Hodgkin's lymphoma.

Whole-body metabolic information provided by 18F-FDG PET could help in the evaluation of lymphoma patients at diagnosis and follow-up. We studied 60 patients, 42 at initial presentation and 18 for disease recurrence (23 aggressive non-Hodgkin's lymphoma, 21 low-grade non-Hodgkin's lymphoma and 16 Hodgkin's disease). All patients underwent a clinical examination, computed tomography (CT) and a non-attenuated PET scan within 1 week. The patients received 222-296 MBq (6-8 mCi) 18F-FDG intravenously and emission scans were recorded 45-90 min later. 18F-FDG PET detected more lymph nodes than the clinical examination or CT, but this rarely resulted in upstaging (two patients). The concordance between PET and CT for the evaluation of the spleen, liver and digestive tract was quite good. Discordance was noted in 12 patients for the evaluation of bone marrow infiltration, but confirmation by MRI or focal biopsy was not always obtained. We conclude that non-attenuated 18F-FDG PET is an easy and efficient whole-body method for the evaluation of patients with lymphomas. Compared with conventional techniques, however, it does not appear to offer much improvement for staging but provides a satisfactory base for follow-up.

Bronchiolitis obliterans organizing pneumonia and ulcerative colitis after allogeneic bone marrow transplantation.

A 37-year-old man with acute myeloblastic leukemia in first remission developed ulcerative colitis and bronchiolitis obliterans organizing pneumonia (BOOP) 7 months after bone marrow transplantation (BMT) from an HLA-matched brother who suffered from severe Crohn's disease. BOOP occurred 20 days after idiopathic interstitial pneumonia, in the context of severe ulcerative colitis. Lung and colon biopsies showed no signs of CMV infection or GVHD. The patient was treated with oral methylprednisolone 1 mg/kg/day and his clinical status and chest X-ray improved slowly. Remarkably, the symptoms of colitis also resolved with prednisone therapy and he is now symptom-free. We hypothesize that ulcerative colitis may have been transmitted from donor to recipient (adoptive autoimmunity) and that it was complicated by BOOP. However, other factors such as CMV may have contributed to the occurrence of BOOP.

[Clinical case of the month. The association of Hodgkin's disease and nephrotic syndrome]. / Le cas clinique du mois. Association d'une maladie de Hodgkin et d'un syndrome néphrotique.

The nephrotic syndrome is a rare complication of Hodgkin's disease. The majority of the cases do not respond to corticosteroids but are cured by the treatment of the lymphoma. We describe a patient with a nephrotic syndrome at the time of diagnosis of mixed cellularity Hodgkin's disease and the resolution of this nephrotic syndrome by MOPP-ABV chemotherapy.

Neutrophilic eccrine hidradenitis. A case report.

Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis occurring most frequently during induction chemotherapy for a variety of malignancies. We report a case of NEH in a 41-year-old woman with acute myeloblastic leukemia under daunorubicin, cytarabine and etoposide chemotherapy. She developed red, tender and painful nodules on a shoulder. The lesions resolved spontaneously. Histological examination is mandatory as the clinical presentation of this dermatosis is highly polymorphic. Leukemia cutis, sepsis, deep fungal infection and Sweet's syndrome must be excluded as these implicate different therapies.

Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation.

Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro.