[French recommendations on control measures to reduce the infectious risk in immunocompromised patients]. / Quelles mesures pour maîtriser le risque infectieux chez les patients immunodéprimés ? Recommandations formalisées d'experts.

The increase use of immunosuppressive treatments in patients with solid cancer and/or inflammatory diseases requires revisiting our practices for the prevention of infectious risk in the care setting. A review of the literature by a multidisciplinary working group at the beginning of 2014 wished to answer the following 4 questions to improve healthcare immunocompromised patients: (I) How can we define immunocompromised patients with high, intermediate and low infectious risk, (II) which air treatment should be recommended for this specific population? (III) What additional precautions should be recommended for immunocompromised patients at risk for infection? (IV) Which global environmental control should be recommended? Based on data from the literature and using the GRADE method, we propose 15 recommendations that could help to reduce the risk of infection in these exposed populations.

[Efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) on the neuropathic manifestations in POEMS syndrome]. / Efficacité à moyen terme de l'autogreffe de cellules souches hématopoïétiques périphériques sur la polyneuropathie du syndrome POEMS: expérience chez 5 cas.

INTRODUCTION: POEMS syndrome (polyneuropathy, organomegaly, endocrynopathy, M-protein, and skin changes) is a rare multisystem disease associated with plasma cell dyscrasia. The efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) reported in case series has been mainly based on hematologic criteria and clinical recovery of peripheral neuropathy dysfunctions but has not been specifically evaluated. This retrospective study aimed to analyze the efficacy of auto-PBSCT on disability and electrophysiological patterns in patients with POEMS syndrome. METHODS: Five patients presenting with POEMS syndrome received auto-PBSCT. Disability was evaluated before treatment and at 6 and 12 months using the Overall Neuropathy Limitation Scale (ONLS) and MRC sumscore of 28 muscles. Nerve conduction studies were performed before and one year after treatment, on median, ulnar, fibular and tibial nerves. RESULTS: Mean age was 60.6 years (49-70). Disease duration between first symptoms and auto-PBSCT was 15.4 months (2-33). Before auto-PBSCT, mean ONLS score was 4.2 (1-10) and mean MRC sumscore 115.8/140 (74-140). At M6, mean ONLS score decreased and mean MRC sumscore increased; both were improved in all patients at M12: mean ONLS score 3 (range 0-8) at M6 and 2.2 (range 0-7) at M12; mean MRC sumscore 118/140 (77-140) at M6 and 122.4/140 (80-140) at M12. Significant recovery in electrophysiological patterns was observed in all patients on ulnar and median nerves: before-after treatment differences were observed for motor conduction velocities (34.41 vs. 45.47 m/s; P<0.001), distal CMAP amplitudes (5.04 vs. 5.96 mV; P=0.004), and sensory conduction velocities (43.20 vs. 49.20 m/s; P=0.001). Distal CMAP amplitude remained low in fibular and tibial nerves (0.41 vs. 0.17 mV). CONCLUSIONS: Clinical and electrophysiological improvement is obvious in POEMS syndrome peripheral neuropathy within one year after treatment with auto-PBSCT, undoubtedly resulting from extensive remyelinisation and axonal regeneration. Further studies are required to examine long-term outcome in patients with POEMS syndrome given auto-PBSCT.

Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine.

Metaphase cytogenetics (MC) has a major role in the risk stratification of patients with myelodysplastic syndromes (MDSs) and can affect the choice of therapies. Azacitidine (AZA) has changed the outcome of patients with MDS or acute myeloid leukemia (AML) unfit for intensive chemotherapy. Identification of patients without the benefit of AZA would allow AZA combination or other drugs in first-line treatments. New whole-genome scanning technologies such as single nucleotide polymorphism microarray (SNP-A)-based molecular karyotyping (MK) improve the risk stratification in MDS and AML. Maintenance of genomic integrity is less than three megabases (Mbs) total disruption of the genome correlated with better overall survival (OS) in patients with lower-risk MDS. In this SNP-A study, we aimed at defining a cutoff value for total genomic copy number (CN) alterations (TGA) influencing the median OS in a cohort of 51 higher-risk MDS/AML patients treated with AZA. We observed that the relative risk of worse OS increased >100 Mb of TGA, as detected by SNP-A-based MK (8 and 15 months respectively, P=0.02). Our data suggest that precise measurement of TGA could provide predictive information in poor and very poor revised International Prognostic Scoring system (IPSS-R) patients treated with AZA.

[Six cases of pulmonary MALT lymphoma: a heterogeneous therapeutic management]. / Six cas de lymphomes pulmonaires de type MALT : une prise en charge thérapeutique hétérogène.

Pulmonary mucosa-associated lymphoid tissue lymphomas (PMALT) account for around 1% of lymphomas. Clinical and radiological presentations, and the treatment of six PMALT were collected from 1993 to 2008. All patients received chemotherapy before disease progression. Two patients had a lobectomy and one received thoracic radiotherapy. In 2008, all the patients were alive and three were in remission. A "watch and wait" strategy is widely accepted for stable, asymptomatic patients and patients with low tumour mass. Surgery may be proposed for symptomatic patients who have localised PMALT. When a chemotherapy treatment is to be suggested, chlorambucil-based chemotherapy is preferred. There may be room for rituximab alone or in combination, but this remains to be precisely defined. Several larger studies are currently ongoing to assess the role of monoclonal antibodies and chemotherapy in MALT lymphomas. Subgroup analysis should help us to define the optimal treatment for PMALT.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

[Necrobiotic xanthogranuloma , a cutaneous disorder associated with monoclonal gammopathy]. / La xanthogranulomatose nécrobiotique, une histiocytose non langerhansienne à expression cutanée associée à une gammapathie monoclonale.

INTRODUCTION: Necrobiotic xanthogranuloma is a rare cutaneous disorder usually associated with monoclonal gammapathy. We describe two new cases. EXEGESIS: A 70-year-old patient was affected by a monoclonal gammopathy. She presented with a diplopia related to a retro-orbital tumor. The biopsy showed inflammatory lesions. Five years later, inflammatory xanthomatous skin lesions appeared. Biopsy specimens gave the diagnosis of necrobiotic xanthogranuloma. A 70-year-old woman was referred for inflammatory cutaneous lesions. Clinical, biological investigations and skin biopsies led to the diagnosis of cutaneous sarcoidosis associated with monoclonal gammopathy. Four years later, she developed a nephrotic syndrome. New skin biopsy specimens showed a necrobiotic xanthogranuloma. CONCLUSION: Necrobiotic xanthogranuloma is a systemic disease. It is a rare non-Langerhans cell histiocytosis characterized by frequent cutaneous and ophthalmologic lesions and associated with monoclonal gammopathy. To our knowledge, retro-orbital involvement has never been reported in necrobiotic xanthogranuloma. Treatment is difficult.

[Cutaneous Waldenström's macroglobulinemia]. / Localisations cutanées de la maladie de Waldenström.

BACKGROUND: We report the case of a patient in whom the first manifestation of Waldenström' s macroglobulinemia was specific skin lesions, treated with chlorambucil chemotherapy. CASE REPORT: A 76-years old woman was referred to us because of chronic red nodular lesions on her face. A biopsy specimen showed a dense lymphocytic dermal infiltrate and immunohistochemistry identified a monoclonal B lymphoid population with an IgM-kappa phenotype. The patient's disease was diagnosed as Waldenström's macroglobulinemia with cutaneous localization, on the basis of a high level of circulating macroglobulinemia and a lymphoplasmocytic infiltrate in the bone marrow expressing the same monoclonal IgM-kappa as in blood and skin. Treatment with radiotherapy (12 Grays) was unsuccessful. Chlorambucil (16 mg per day, 7 days per month) was then introduced with rapid disappearance of the skin lesions. Neutropenia led to withdrawal of this treatment after 4 courses. The skin lesions relapsed 18 months later and were cured with chlorambucil at a lower dose. DISCUSSION: Specific skin infiltrates have been rarely described during Waldenström's macroglobulinemia. Review of the literature showed eight cases of such lesions treated by chemotherapy with only two successes with oral cyclophosphamide and polychemotherapy (cyclophosphamide, vincristine and CCNU). Chlorambucil was used unsuccessfully three times. We hypothesize that primary resistance to alkylating-agent and the small number of cases of cutaneous Waldenström's macroglobulinemia may explain the poor response to systemic chemotherapy previously reported.

[Anti-TNF alpha monoclonal antibodies (infliximab) and tuberculosis: apropos of 3 cases]. / Anticorps anti-TNF alpha (infliximab) et tuberculose: à propos de trois cas.

INTRODUCTION: Monoclonal TNF alpha antibodies are a new treatment of severe rheumatoid arthritis. One of the possible side effects is the appearance of opportunistic infections. We report here on three cases of disseminated tuberculosis observed in patients undergoing treatment with infliximab. EXEGESIS: A 45-year-old woman, treated with infliximab, was hospitalised after five infusions for fever and dyspnoea. The exams showed pulmonary and peritoneal tuberculosis. The second case is a 75-year-old woman whose symptoms were fever, cough and cervical adenopathy after three infliximab infusions. Diagnosis was disseminated tuberculosis. The third case is a 59-year-old man who was hospitalised for an infectious syndrome with dyspnoea, after two infliximab infusions. We discovered pulmonary tuberculosis. CONCLUSION: These three cases added to the 68 cases of tuberculosis registered with the treatment of infliximab. This confirms the risk of severe opportunist infectious side effects. TNF alpha is a cytokine which has anti-infectious properties. These tuberculoses are severe and generalized. It is recommended to search for an active or latent tuberculosis before beginning treatment with infliximab, and to check these patients frequently.

[Primary hyperparathyroidism, a differential diagnosis of motor neuron diseases]. / Hyperparathyroïdie primitive, un diagnostic différentiel des maladies du motoneurone.

INTRODUCTION: Motor neuron diseases are always lethal. Other curable causes of neurologic disorders have to be sought. We report an example. EXEGESIS: A 72-year-old man presented a distal weakness and atrophy of the upper extremities. Electromyography showed thenar and hypothenar denervation, without fasciculation. Hypercalcemia led to the discovery of a primary hyperparathyroidism. Five months after parathyroid surgery, there was no worsening. CONCLUSION: Von Recklinghausen and Vical were the first to describe neuromuscular involvement in primary hyperparathyroidism. Faced with symptoms mimicking motor neuron diseases, calcium and phosphorus levels have to be measured because hyperparathyroidism can be cured and neurologic disorders disappear after surgery.

Effect of indinavir and higher CD4+ T-cell count on viral load response after 6 months of highly active antiretroviral therapy.

This retrospective, unmasked chart review was undertaken to determine which HIV-infected patients receiving protease inhibitors (PIs) for the first time were most likely to experience a decrease in plasma viral load (PVL) and which factors were associated with a PVL < 500 copies/mL below the detectable limits after 6 months. A total of 308 patients aged > 15 years with a PVL > 500 copies/mL received therapy that included a PI in addition to other antiretroviral therapies (128 patients, saquinavir hard-gel capsule 600 mg TID; 107 patients, indinavir 800 mg TID; and 73 patients, ritonavir 600 mg BID). The choice of drug was at individual clinicians' discretion. Patients were followed for a median of 10 (range, 6 to 21) months. Of the 128 patients who received saquinavir, 45% were switched to another PI (33%, indinavir; 12%, ritonavir). Seventy percent of the 73 patients initially given ritonavir were switched (45%, indinavir; 25%, saquinavir), as were 23% of the 107 patients initially given indinavir (15%, saquinavir; 8%, ritonavir). A total of 34.1% (n = 105) of patients achieved a PVL < 500 copies/mL; in 51.6%, PVL decreased > 0.5 log copies/mL. In this subgroup, both treatment-naive patients and those who were receiving a new combination of antiretroviral therapy when they started PI treatment had a more pronounced decline in PVL (P < 0.001). After adjustment by logistic regression analysis for age, sex, mode of transmission, and duration of highly active antiretroviral therapy (HAART), CD4+ cell count and initial type of PI received were independently associated with PVL < 500 copies/mL. In the present study, the treatment success rate was low (34.1%) compared with rates observed in randomized, controlled trials. A higher CD4+ cell count and use of indinavir at the initiation of HAART are associated with a better viral load response.

Familial multiple myeloma: report of fifteen families.

To further define the frequency, clinical and biological features of familial multiple myeloma we performed a retrospective study of related patients who presented with multiple myeloma. Most cases of familial multiple myeloma were observed in siblings (10/15), in whom the mean age at diagnosis was similar to unrelated multiple myeloma. In successive generations the mean age at diagnosis was lower. Monoclonal component was identical (IgG kappa) in seven families. Familial history of monoclonal gammopathy of undetermined significance was observed in three families. Five other prospective studies of 1263 patients identified four affected families (3.2 per 1000 cases of multiple myeloma), and raise the question of a genetic background in multiple myeloma.

[Influence of HIV-related immunodeficiency on the histopathology of chronic hepatitis C]. / Influence du déficit immunitaire lié au VIH sur l'histopathologie des hépatites chroniques C.

OBJECTIVE: There is substantial evidence demonstrating the aggravating effect of human immunodeficiency virus (HIV) infection on the progression of chronic hepatitis C virus (HCV) infection. There is however, little data on the affect of certain factors which could affect liver pathology findings in patients with concomitant HIV infection such as the duration of HIV infection or T-cell subpopulation counts. We examined pathology findings in patients with concomitant HIV and HCV infections to determine the impact of immunodepression. PATIENTS AND METHODS: We reviewed liver pathology data collected in patients with concomitant HIV and HCV infections grouping patients according to severity of the liver pathology: group 1 = cirrhosis or active hepatitis; group 2 = minimally active hepatitis or histologically normal liver. Transparietal liver biopsies were obtained for the work-up of viral hepatitis or because of long-term unexplained fever or suspected lymphoma. Epidemiological and biological data were obtained from medical files. The duration of the liver disease was estimated from the date of exposure to risk of immunodepression as determined by the peripheral CD4+ and CD8+ counts. All pathology specimens were read by two pathologists who established the Knodell score for each patient. RESULTS: Fifty patients were included: 23 were classed in group 1 and 28 in group 2. The Knodell score was significantly different between the two groups, 11 +/- 4 and 4 +/- 3 respectively (p < 0.0001). Disease duration was similar for the two groups: mean 8 years. Mean CD4+ count was significantly higher in group 1: 312/mm3 versus 110/mm3 for group 2 (p = 0.0057); as was the mean CD8+ count (758/mm3 versus 360/mm3, p = 0.0013). For the entire study population, there was a significantly negative correlation (p < 0.05) between the Knodell score and the CD4+ count (r = 0.31) and for the CD8+ count (r = 0.41). CONCLUSION: HCV-related liver pathology in patients co-infected with HIV depends on the level of immunodepression. CD8+ counts are better correlated with pathology findings than with CD4+ counts.

[Peritoneal benign polycystic mesothelioma]. / Le mésothéliome polykystique péritonéal bénin.

BACKGROUND: Benign multicystic peritoneal mesothelioma (BMPM) is an uncommon condition. CASE REPORT: We observed a typical case of BMPM occurring in a 57-year-old man who presented with a painful mass of the lower right quadrant. The pathology using immunostaining gave the diagnosis. DISCUSSION: The diagnosis of BMPM can be suspected on the basis of imaging findings, but is usually confirmed by pathology. The only treatment for BMPM is surgical resection. Prognosis is good despite frequent recurrences. Two main hypotheses based on etiopathology can be discussed: does BMPM consist of a mesothelioma proliferative and reactional lesion or is it a real mesothelioma tumor?

[Lung cancer in patients infected with human immunodeficiency virus. Clinical course and therapeutic implications]. / Cancer du poumon chez les malades infectés par le virus de l'immunodéficience humaine. Particularités évolutives et implications thérapeutiques.

OBJECTIVES: HIV infection is associated with increased frequency of non-Hodgkin's lymphoma and Kaposi sarcoma. Like other malignancies, lung cancer has been described in HIV-infected patients although no evidence of a statistical correlation has been reported. PATIENTS AND METHODS: We performed a retrospective analysis of 15 HIV-infected patients with lung cancer. The patients were relatively younger (mean age 45 years) than is commonly found in lung cancer cohorts. RESULTS: The 15 patients had mild immunodepression (240 CD4+/mm3) and were in advanced clinical stage at diagnosis. Mean overall survival was 6 months and no clinical or biological prognostic factors were found. Death was usually due to infection, suggesting a synergetic effect between HIV and chemotherapy-induced immunodepression. CONCLUSION: We propose early antiretroviral therapy in cases of chemotherapy-treated HIV patients, even when commonly accepted immunological and/or clinical criteria are absent.