A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group.

A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, an analytic hierarchy process (AHP), a multiple-attribute decision-making technique, was used. The steps consisted of selecting the candidate criteria for defining resistance/intolerance; identifying the motivations that could influence the preference of the WG for any individual criterion; comparing the candidate criteria in a pair-wise manner; and grading them according their ability to fulfill the motivations. Every step in the model was derived by questionnaires or group discussion. The WG proposed that the definition of resistance/intolerance should require the fulfillment of at least one of the following criteria: platelet count greater than 600,000/micro l after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400,000/micro l and WBC less than 2500/micro l or Hb less than 10 g/dl at any dose of HU; presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU; HU-related fever.     

Dominant form of vanishing white matter-like leukoencephalopathy

Leukoencephalopathy with vanishing white matter syndrome (childhood ataxia with central nervous system hypomyelination/vanishing white matter disease) is an autosomal recessive disorder characterized by the occurrence of acute episodes of deterioration after minor head trauma or infection, and symmetrical demyelination on magnetic resonance with cavitation aspects. Mutations in each of the five subunits of eIF2B have been identified. We report in an affected man and his mother an adult-onset form of childhood ataxia with central nervous system hypomyelination/vanishing white matter disease-like disorder with no mutations in the EIF2B genes and normal guanine nucleotide exchange factor eIF2B activity, suggesting a new dominant inheritance of this syndrome that may involve other genes.     

Intrathoracic coelomic cysts]

Intrathoracic coelomic cysts are benign embryonic tumors with a mesothelial lining. The aim of this work was to review possible localizations (pleuropericardic and other), the remaining surgical indications, and the current situation of minimally invasive techniques. We reviewed retrospectively, 28 cases of intrathoracic coelomic cysts in 12 men and 16 women, mean age 44 years. We recorded the cyst localization, clinical signs, indication for surgery, access routes used, and outcome. Twenty-one cysts were pleuropericardial cysts and 7 were ectopic mediastinal cysts. In all 7 of the ectopic mediastinal cysts and 4 of the pleuropericardial cysts surgery was indicated for diagnosis; for the other pleuropericardial cysts the indication was based on clinical signs (n = 4), large volume (n = 4), progressing volume (n = 7), no apparent reason (n = 1) and association with surgery for pneumothorax (n = 1). Assess was by mediastinoscopy (n = 1), mediastinotomy (n = 1), sub-xyphoid route (n = 1), thoracotomy (n = 18), and videothoracoscopy (n = 7). Long-term outcomes (mean follow-up 4 years 4 months) were good with no recurrences. Postoperative sequelae were observed in 6 cases after thoracotomy and in 1 case after videothoracoscopy. In summary, pleuropericardial cysts warrant surveillance without surgery unless their volume increases or clinical signs develop. Ectopic mediastinal cysts usually require surgery for diagnosis. It would appear advisable to prefer videothoracoscopy which allows diagnosis and excision of pleuropericardial cysts. Minimal thoracotomy may be helpful for ectopic mediastinal cysts.     

Therapeutic approach to post-radiation xerostomia. A reservoir prosthesis and an artificial salivary gland

Radiation-induced xerostomia is an incapacitating sequela of salivary gland irradiation in patients receiving tumoricidal X-ray therapeutical doses for cancer of the upper respiratory and gastrointestinal tracts. All stimulant type therapeutics available are powerless to bring back wetness into the mouth of patients with asialia. Replacement therapy constitutes the only alternative for symptomatic treatment. Artificial salivary gland sprays have a proven unsustained, short-lasting efficacy. The administration of an oral mucine-containing salivary emollient solution drip, presented either in the form of an oral or external container, constitutes an original symptomatic treatment regimen, the efficacy of which has been established. The authors here review the concept and methodology of their palliative treatment protocol against chronic asialia.     

Pain management in end-of-life care, representations, realities and advances

Pain management is essential at every stage of a disease. At the end of life, healthcare professionals are increasingly attentive to the discomfort each treatment may cause. The recent publication of recommendations offers new perspectives with regard to situations of intractable pain.     

Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study

Low baseline NK-cell counts (NKCCs) in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a poor prognosis. The REMARC phase III trial (NCT01122472) showed that lenalidomide maintenance prolonged PFS in rituximab–chemotherapy responders. We conducted a REMARC ancillary study analysing the impact of lenalidomide maintenance on the prognostic value of low NKCCs. Blood samples from 335 elderly French patients enrolled in the REMARC trial were analysed by flow cytometry to obtain NKCCs at diagnosis (n = 220), at randomization (n = 186) and/or six months after randomization (n = 184). Baseline NKCCs < 100 cells/μl were associated with shorter PFS and OS (HRs = [2.2 (1.4, 3.3), p < 0.001] and [2.8 (1.7, 4.5), p < 0.001], respectively), independently of aaIPI. In a competing risk analysis, low NKCCs at baseline were associated with a higher risk of relapse/progression (p = 0.0025), but not of death without progression (p = 0.33). Lenalidomide did not affect the prognosis value of low baseline NKCCs (p  = 0.6349). Similar results were obtained for low NKCCs at randomization. Our results demonstrate that low NKCCs at baseline and post rituximab–chemotherapy are robust prognostic factors in DLBCL and reveal that lenalidomide has no impact on this parameter. Other therapeutic strategies aiming at improving NK-cell function could improve outcomes in DLBCL.     

How to define intermediate stage in Hodgkin's lymphoma?

Abstract:  Background : Intermediate or unfavourable stage Hodgkin's lymphoma (HL) definition relies upon at least three different scoring systems defined by cooperative groups (EORTC, GHSG and Canadian-ECOG). We aimed to investigate their efficacy and their correlation with International Prognostic Score (IPS) for advanced HL. Patients and methods : We studied a population of 1156 patients with localized stage HL treated prospectively within GELA centres in H8 (518 patients) and H9 (638 patients) protocols. Median age: 30 yr, 18%, Female 50%; stage I: 25%; stage II: 75%. According to scoring systems 70% had 0–1 EORTC factors; 60% 0–1 GHSG factors and 82% 0–1 Canadian factors. The IPS for advanced stages was available only in H9 study with 64% 0–1 factor. Results : Survival curves according to each of the different scoring systems could significantly discriminate the subgroup populations. When a multivariate Cox analysis was performed for overall survival (OS) including all the scoring system variables: age >45 yr, sex male, Haemoglobin <10.5 g/dL, lymphocytes <600/ μ L, B symptoms with elevated ESR, extra nodal sites did retain an independent significant value. Probability of OS was 99%, 98%, 92%, 82% and 73% for patients with 1–5 factors, respectively P  < 0.0001. Conclusion : These factors are similar for most of them with those described in the IPS when stages III and IV are replaced by extra nodal localization. This new score should be validated in other prospective trials, as it will simplify the Hodgkin prognostic scoring systems for localized and advanced stages.