French protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases.

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.

[Autologous hematopoietic stem cell transplantation for chronic inflammatory demyelinating polyneuropathy]. / Carrefour des spécialités : autogreffe de cellules souches hématopoïétiques périphériques pour la prise en charge thérapeutique des polyradiculonévrites inflammatoires démyélinisantes chroniques.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a dysimmune neuropathy with sensory and/or motor symptoms due to destruction of the myelin sheat secondary to an auto-immune attack. A quarter to a third of patients do not respond to immunomodulatory first line recommended therapies. No second line treatment has shown its effectiveness with a sufficient level of evidence. Autologous hematopoietic stem cell transplantation (AHSCT) is a promising therapy for autoimmune disease, especially for CIDP in recent works. We present in this article an update on the diagnosis of CIDP, its conventional treatments as well as the results of AHSCT in this indication, which was the subject of French recommendations under the aegis of the SFGMTC and neuromuscular disease french faculty (FILNEMUS) as a third line therapy after failure of two first-line and one second-line treatments.

R-CHOP appears to be the best first-line treatment for second primary diffuse large B cell lymphoma: a cancer registry study.

Second primary diffuse large B cell lymphoma (spDLBCL) is defined as a metachronous tumor occurring after a first primary cancer. To date, while R-CHOP is the standard first-line treatment for de novo DLBCL, no available data show that R-CHOP is the optimal treatment for spDLBCL. This exploratory study aimed to investigate treatment of spDLBCL. From 2008 to 2015, the Poitou-Charentes general cancer registry recorded 68 cases of spDLBCL ≤ 80 years old, having received a first-line treatment with either R-CHOP (78%) or other regimens (22%). Patients without R-CHOP have worse overall survival in univariate (HR 2.89 [1.33-6.24], P = 0.007) and multivariate (HR 2.98 [1.34-6.67], P = 0.008) analyses. Patients without R-CHOP more frequently had PS > 1 (67% vs. 28%, P = 0.007) and prior chemotherapy (60% vs. 26%, P = 0.02), which suggests that both of these factors influence a clinician's decision to not use R-CHOP. Prior chemotherapy had no prognostic impact in univariate and multivariate analyses; this result could call into question the risk-benefit balance of not using R-CHOP to prevent toxicity. In our study, one DLBCL out of ten occurred after a first primary cancer, and as regards de novo DLBCL, R-CHOP appeared to be the best first-line treatment. Larger series are needed to confirm these results.

Observational study of vaccination in cancer patients: How can vaccine coverage be improved?

BACKGROUND: Chemotherapy increases the risk of infections, often severe, and some of them are vaccine-preventable infections. We aimed to assess vaccination coverage and associated factors in oncology and hematology patients. METHODS: Consecutive adult patients followed in a French university hospital for hematological malignancy or solid cancer voluntarily completed an anonymous questionnaire in September and October 2016. It included questions on underlying disease, chemotherapy, flu, and pneumococcal vaccination uptakes, and attitudes toward vaccination. Factors associated with vaccination uptake were assessed by multivariate logistic regression. RESULTS: The response rate was 41.9% (N=671) among 1,600 questionnaires distributed; 232 patients had underlying hematological malignancy and 439 had solid cancer. Half of the patients were aged over 65 years. Chemotherapy was ongoing or discontinued for less than one year in 74.7% of patients. In patients aged <65 years undergoing chemotherapy, flu vaccination rate was 19.9% whereas patients aged >65 years had coverage of 47%. Pneumococcal vaccine uptake was 7.3%. However, 64.7% of patients were favorable to vaccination. Vaccine uptake was associated with age >65 years (OR 4.5 [2.9-7.0]), information about vaccination delivered by the family physician (OR 12.9 [5.5-30.1]), follow-up in hematology unit (OR 2.0 [1.3-3.1]), and positive opinion about vaccination (OR 2.0 [1.3-3.1]). CONCLUSION: Despite specific recommendations regarding immunocompromised patients, anti-pneumococcal and flu vaccinations were rarely conducted, even in elderly patients. Targeted information campaigns to family physicians, oncologists, and patients should be implemented to improve vaccine coverage in patients with underlying malignancies.

Is current initial empirical antibiotherapy appropriate to treat bloodstream infections in short-duration chemo-induced febrile neutropenia?

INTRODUCTION: Fever of unknown origin is by far the most common diagnosis in low-risk febrile neutropenic patients undergoing chemotherapy. The current empirical regimen combines amoxicillin-clavulanic acid and fluoroquinolones in low-risk neutropenic patients. The aim of this study was to assess the appropriateness of antibiotherapy and the outcome of bloodstream infections (BSI) in patients with expected neutropenia of short duration. METHODS: This 2-year monocentric retrospective study included all consecutive neutropenic febrile adult patients with expected duration of neutropenia ≤ 7 days. They were classified into low- and high-risk groups for complications using the MASCC index. Appropriateness of initial empirical antibiotic regimen was assessed for each BSI. Multivariate analysis was performed to identify factors associated with mortality. RESULTS: Over the study period, 189 febrile episodes with positive blood cultures in neutropenic patients were reported, of which 44 occurred during expected duration of neutropenia ≤ 7 days. Patients were classified as high-risk (n = 27) and low-risk (n = 17). Gram-negative bacteria BSI represented 57% of cases, including only two multidrug-resistant bacteria in high-risk patients. Initial empirical antibiotherapy was appropriate in 86% of cases, and inappropriate in the event of coagulase-negative Staphylococcus BSI (14%), although the outcome was always favorable. In low-risk patients, no deaths and only 12% of severe complications were reported, contrasting with mortality and complication rates of 48% (p < 0.001) and 63% in high-risk patients (p < 0.001), respectively. CONCLUSIONS: Outcome of BSI is favorable in low-risk febrile neutropenic patients, even with inappropriate empirical initial antibiotic regimen for coagulase-negative Staphylococcus BSI. Initial in-hospital assessment and close monitoring of these patients are however mandatory.

Vaccination of cancer patients treated with chemotherapy: A survey among general practitioners.

OBJECTIVES: Despite specific recommendations issued by the French Public Health Council (Haut Conseil de Santé Publique), the vaccination coverage of patients with cancer or malignant blood disease remains insufficient. The aim of this study was to assess the vaccination of chemotherapy patients by their general practitioner (GP). METHODS: A survey was conducted between March and July 2017 in 4 French departments to describe the immunization practices of GPs for their chemotherapy patients and provide solutions to help to increase the vaccination rate. RESULTS: Of the 1610 GPs who received the questionnaire, 287 (17.8%) returned a usable form; 92.6% were globally pro-vaccine. One third of GPs (37.3%) declared that they vaccinated all their chemotherapy patients. The GPs (n=180) who never or only sometimes vaccinated their chemotherapy patients mainly voiced concerns about not being properly trained (45.6%) and the lack of easily available information on vaccination (35.0%). Three-quarters (n=212; 74%) of the GPs wanted to improve their level of medical knowledge via continuing education (52.4%) or by reading guidelines available on-line (39.6%). GPs suggested that a specific vaccination schedule be included in the letter they receive from the cancer specialist (72.8%) and that patient awareness be increased (50.5%). CONCLUSIONS: GPs are in favor of the vaccination of cancer patients. The main obstacles stated are the lack of education and the lack of easily available information. Vaccination coverage could be increased by improving the doctor-to-doctor relation between GPs and cancer specialists.

[Free light chains assay: Indications and methods]. / Dosage des chaînes légères libres : indications et méthodes.

Serum free light chains (sFLC) assay is an important marker in plasma cell dyscrasia. It is thus recommended for the diagnosis of monoclonal gammopathy, together with serum protein electrophoresis and immunofixation. sFLC assay has also a prognostic value and is a criterion for treatment response and relapse of some monoclonal gammopathies. Three assays are currently available in France, the gold standard being the Freelite® assay, the two others requiring further validation. These three assays are not interchangeable during patient's follow-up. The Freelite® assay is integrated in the myeloma diagnostic criteria from the International Myeloma Working Group 2014, and has a higher sensitivity than Bence Jones protein test for diagnosis, treatment response and follow-up of light chain myeloma. The Freelite® assay is the main marker of therapeutic response in light chain amyloidosis and allows to stratify the risk for progression in monoclonal gammopathy of undetermined significance. Some studies have also shown its value in diagnosis of multiple sclerosis and in screening for monoclonal gammopathy in the cases of acute renal failure. The Freelite® assay is then currently essential in myeloma or amyloidosis, and could be soon extended to the management of autoimmune diseases.

[Relapse of acute promyelocytic leukemia in the central nervous system revealed by isolated dementia]. / Récidive neuroméningée d'une leucémie aiguë promyélocytaire révélée par un syndrome démentiel isolé.

INTRODUCTION: Approximately 1.5% of dementia is due to curable aetiology. We report an isolated dementia syndrome due to a meningeal relapse of acute promyelocytic leukaemia with favourable outcome after appropriate treatment. CASE REPORT: A 72-year-old woman, in remission of an acute promyelocytic leukaemia, presented a loss of autonomy for several months due to corticosubcortical dementia. Lumbar puncture showed blast cells indicating meningeal relapse of leukaemia. Intrathecal chemotherapy and arsenic trioxide obtained biological and molecular remission as well as restoration of normal cognitive functions. CONCLUSION: In patients with hematologic past history such as acute promyelocytic leukaemia, an isolated cognitive impairment should alert physicians to search for an isolated neuromeningeal relapse.

Multiple myeloma: the quality of care is linked to geographical and organisational determinants. A study in a French registry.

Multiple myeloma is a haematological malignancy whose care is spread over several specialities and provided by centres that various sizes, which raises the issue of equal opportunities in care access. Incident cases of myeloma between 2008 and 2010 were exhaustively identified by the Poitou-Charentes Cancer Registry. To ascertain the quality of care, the diagnosis, staging, and treatment administered were compared to international recommendations. Three hundred and sixty-seven patients were included. The diagnostic procedure exhibited 98% compliance, the staging 58%, and treatment 89%. Concerning diagnostic and staging, non-compliance with recommendations was associated to the failure to perform collegiate case assessments in multidisciplinary team (MDT) meetings [OR 2.15 (1.15-4.04)], care provided at a secondary centre, and a distance between home and the centre of 5-25 km [2.16 (1.06-4.40)] and 25-50 km [2.86 (1.37-6.01)]. Regarding treatment, non-compliance with recommendations was associated with care provided at a secondary centre [5.28 (2.03-13.75)]. Finally, diagnosis, staging and treatment quality improved over time. This study underlines the need to improve the organisation of the healthcare offer, so that patients can receive the best possible care. MDT seems to be the main means to improve quality of care.