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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.

La neutropenie est definie par une baisse du nombre absolu de polynucleaires ou par une dysfonction de ces derniers. Elle est source de complications pouvant necessiter une admission en reanimation. Les specificites de prise en charge des patients neutropeniques admis en reanimation ont motive ce referentiel. Ces recommandations ont ete realisees sous l’egide de la Societe de reanimation de langue francaise (SRLF) par un panel d’experts choisis au sein de la SRLF, du Groupe francophone de reanimation et d’urgences pediatriques (GFRUP), de la Societe francaise d’anesthesie et de reanimation (Sfar), de la Societe francaise d’hematologie (SFH), de la Societe francaise d’hygiene hospitaliere (SF2H) et de la Societe de pathologie infectieuse de langue francaise (SPILF). L’analyse du niveau de preuve et la formulation des recommandations ont suivi la methode « GRADE » (grading of recommendations assessment, development and evaluation system). Les recommandations ont ete cotees selon la methode RAND/UCLA. Six champs ont ete definis : 1) admission en reanimation et pronostic ; 2) isolement et prophylaxies ; 3) diagnostic des complications respiratoires ; 4) prise en charge des complications viscerales ; 5) traitements anti-infectieux : antibiotherapie et controle de la source ; 6) prise en charge hematologique. La plupart des recommandations sont de bas niveau de preuve, soulignant les besoins d’etudes specifiques dans cette population. Cependant, sept recommandations de haut niveau de preuve ont pu etre formulees concernant l’isolement protecteur, la strategie diagnostique de l’insuffisance respiratoire aigue, la prise en charge medicale et le delai de la chirurgie de l’enterocolite du neutropenique.

To the Editors: Bronchiolitis obliterans (BO) following allogeneic haematopoietic stem cell transplantation (HSCT) is recognised as a pulmonary manifestation of chronic graft- versus -host disease (GVHD) [1, 2]. As lung biopsy is rarely performed in these patients, the diagnosis of BO syndrome (BOS) usually relies on pulmonary function testing (PFT) and computed tomography (CT) lung scans [1, 2]. Very little retrospective data exist regarding the treatment of BOS, which currently consists of increasing a patient’s baseline dose of systemic immunosuppressive therapy; however, this treatment strategy has been shown to have poor efficacy [2, 3]. The efficacy of new drugs for the treatment of chronic GVHD, including the anti-CD20 monoclonal antibody rituximab, must be specifically evaluated for BOS. Here, we report three cases in which patients received rituximab for BO after allogeneic HSCT. Patient 1 was a 15-yr-old male who received bone marrow from a sibling human leukocyte antigen (HLA)-matched donor for acute myeloid leukaemia after a myeloablative conditioning regimen that included 12 Gy fractionated total body irradiation (FTBI) and cyclophosphamide. 5 months after transplantation, he was diagnosed with chronic liver GVHD that led to the initiation of prednisone at a dosage of 1 mg·kg−1·day−1 as well as tacrolimus. 8 months after transplantation, as his liver GVHD was coming under control, he presented with dyspnoea, dry cough and chest pain. At this time, he was receiving tacrolimus and prednisone at a dosage of 20 mg·day−1. PFT revealed a severe obstructive pattern based on a forced expiratory volume in 1 s (FEV1) of 1.13 L (33% predicted), a forced vital capacity (FVC) of 2.79 L (65% pred) and FEV1/FVC ratio of 41%. A lung CT scan demonstrated the presence of air trapping and a …

Invasive aspergillosis (IA) is a major opportunistic infection in haematology patients. Spore inhalation is the usual route of Aspergillus infection, suggesting a determining role of environmental contamination by spores in the epidemiology of IA. We prospectively examined the relationship between environmental contamination by Aspergillus and other fungal species and the incidence of invasive nosocomial aspergillosis (INA) in a bone marrow transplantation unit and two haematology wards. During a four-year period, levels of air and surface fungal contamination were determined bi-monthly in patients' rooms (some equipped with HEPA filters and LAF systems), and various common sites in each ward (corridors, nursing stations, etc.). Results were compared to the incidence of INA. A total of 3100 air and 9800 surface samples were collected, and 79 cases of IA were diagnosed, of which 64 were probably or possibly INA. Patterns of fungal contamination were comparable in the three wards, with a gradient ranging from high levels in common sites to a virtual absence in rooms equipped with HEPA filters and LAF systems. Using a regression model, a significant relationship was found between the incidence of INA and the degree of fungal contamination of air and surfaces in conventional patient rooms (not equipped with HEPA) and common sites. This study shows that in a non-epidemic setting, there is a significant relationship between environmental fungal contamination in haematology wards and the incidence of INA. Our findings underline the importance of environmental surveillance and strict application of preventive measures.

Fungi are becoming a serious public health hazard, especially for the growing numbers of immunocompromised patients in hospitals. These numbers will only increase and cancer patients will be at greater risk for developing fungal infections as the incidence of cancer continues to rise and as treatment strategies become more aggressive. Along with the increased incidence of fungal infections, established fungal pathogens are beginning to exhibit drug resistance, and new pathogens with reduced susceptibility to older antifungal drugs are emerging. The mortality rates using amphotericin B in Candida sepsis and aspergillosis in cancer patients are still high. Therefore, newer antifungal drugs, such as the triazoles fluconazole and itraconazole, as well as new modalities to administer amphotericin B (lipid formulations) have been developed in the hope of diminishing the toxicity and improving the response rates obtained with amphotericin B. A more thorough study of the epidemiology of fungal infection in cancer patients can help to determine which patients are most likely to develop infection. Thus, more intensive monitoring and diagnostic efforts will improve the rapidity and accuracy of diagnosis of fungal infection and can improve patient outcome by allowing intervention at an earlier point in the onset of invasive disease. Genetic typing of fungal species and strains can be used to identify drug resistant organisms. There is an urgent need for the development of new antifungal agents that attack fungal organisms at different sites than those targeted by currently available drugs. Finally, the value of large, well-controlled clinical studies of antifungal agents, as well as the use of growth factors in certain types of cancers, can greatly increase our understanding of the most effective means of treating disseminated fungal disease in the immunocompromised cancer patient.

PURPOSE: To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease. RESULTS: With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome. CONCLUSION: BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.

Over the last 25 years, the numbers of hematopoietic stem cell transplant (SCT) patients have increased rapidly. Infections have been major obstacles for successful transplantation. Thus, infection prevention is very important in transplant recipients. As the results of transplantation have improved, the number of long-term survivors has increased. Vaccination is a potentially important strategy for reducing the risk for vaccine-preventable infections after SCT. The EBMT produced recommendations for vaccination of SCT recipients published in Bone Marrow Transplantation in 1995. This paper updates the previous recommendations based on current knowledge.

Aim: T-prolymphocytic leukemia (T-PLL) is a rare disease of the elderly characterized by a high white blood cell count and organomegaly, and is currently incurable. Our aim was to elicit graft-versus-leukemia reactions in a patient with T-PLL. Methods: A 52-yr-old woman with refractory T-PLL underwent a nonmyeloablative regimen followed by allogeneic peripheral blood stem cell transplantation (a “minitransplant”) from her HLA-matched sibling. Results: There was no treatment related toxicity other than neutropenia. Engraftment was successful. The patient experienced no graft-versus-host disease (GVHD) at any time but, on day 84 after transplantation, had a relapse in the central nervous system. Despite infusion of donor lymphocytes and intralumbar chemotherapy, she died on day 157 of systemic disease. Conclusion: The reasons why treatment may have failed are discussed (nature of disease, disease progression, treatment schedule).

To determine prognostic factors for survival in bone marrow transplant recipients with invasive aspergillosis (IA), we retrospectively reviewed 27 IA cases observed in our bone marrow transplantation unit between January 1994 and October 1994. On 30 September 1997, six patients were alive and disease-free. The median survival after IA diagnosis was 36 days. Of eight variables found to be related to survival according to the univariate analysis, graft-versus-host disease (GVHD) status at IA diagnosis (P = .0008) and the cumulative prednisolone dose taken during the week preceding IA diagnosis (CPDlw) (P.0001) were selected by a backward stepwise Cox regression model. A three-stage classification was established: CPD1w ofor =7 mg/kg (3 of 8 patients died; 60-day survival rate, 88%), CPD1w of7 mg/kg and no GVHD (9 of 10 patients died; 60-day survival rate, 20%), and CPD1w of7 mg/kg and active acute grade 2 or more or extensive chronic GVHD (9 of 9 patients died; 30-day survival rate, 0) (P.0001).

To the Editor: We read with great interest the article by Yaffe et al. [1] They described reversible MRI abnormalities after seizures. These MR abnormalities occurred in both gray and white matter, and most patients were under chemotherapy. Although three patients received intrathecal methotrexate, known to produce radiologic changes in the white matter but not in the gray matter, one of their patients received cyclosporine and another, cisplatinum. …

Subacute thrombosis of the right anterior tibial artery occured in a bone marrow transplant recipient during onset of varicella and was effectively related to varicella zoster virus in a patient under cyclosporine.

Resume Un patient traite pour une infection mycotique severe, due a Candida tropicalis et Cryptococcus neoformans compliquant l'evolution d'une hemopathie maligne, decede de facon brutale a l'arret du traitement. L'autopsie confirme une infiltration elective du muscle cardia que par le cryptocoque. Cette localisation rare a ete exceptionnellement rapportee dans la litterature et la gravite du pronostic justifie qu'elle soit recherchee chez tout patient presentant une cryptococcose.

“Leukaemia” by itself is a term which is understood by the general public as well as by most doctors to mean a lethal disease or a group of lethal diseases.

The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.

Thirty-seven patients with primary unresectable bronchogenic carcinoma were treated by a combination, (“E.M.O.B.”), of cyclophosphamide (40 mg/k on day No. 1, or 13·3 mg/k × 3 consecutive days), methotrexate (7·5 mg/m2/d × 6 d, given orally for 6 consecutive days from day 21 to 26), Folinic Acid (15 mg/m2, IM, on day 27 at 8 p.m.). vincristin (0·7 mg/m2, IV at 8 a.m. on days 28 and 31) and bleomycin (10 mg/m2, IM at 2 p.m. on days 28 and 31, i.e. 6 hr after vincristin. The response was evaluated on day 48 and a new course started on day 49 if a regression or a stabilisation had been obtained. The 37 cases include 9 small anaplastic carcinomas, 24 squamous cell and large cell anaplastic carcinomas, and 4 cases of undetermined type. Thirty-one patients received almost 1 course of the schedule. Among them, 1 had a complete regression, 5 a regression of more than 50%, 6 a regression of less than 50%, 14 a stabilisation. There were 11 failures. Among 12 objective responders (39%) there were 4 squamous cell carcinomas (22%, median duration: 5 months), and 8 oat cell carcinomas (89%, median duration: 4 months). Four out of 37 patients (10%) were alive after 1 yr. The toxicity was evaluable in 32 cases representing 77 courses of the schedule: in 3 cases a severe toxicity led to an interruption of the treatment; strong (4 cases) or tolerable (15 cases) toxicity included nausea, vomiting and marrow depression. In 10 cases there were no toxic phenomena (31%). The over all results of this combination are not significantly better than those that may be obtained with cyclophosphamide or methotrexate as single agents or with vincristin and bleomycin in combination.

Contains fulltext : 193204.pdf (Publisher’s version ) (Closed access) The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

International audience; Surgery and antifungals are the reference standard for rhino-orbito-cerebral mucormycosis (ROCM) treatment. The impact of local control on survival of 22 consecutive ROCM adults was studied on day 90: none vs. 75% died, respectively, with or without local control (p