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The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. The median overall follow-up of the patients was 13.5 years (range 3 months to 16.7 years). Based on intention-to-treat analyses, at 15 years, overall and progression-free survival were similar across arms: 85%, 83%, 80%, and 82% and 84%, 87%, 79%, and 79% for the IM 400 mg (N = 223), IM 600 mg (N = 171), IM 400 mg + AraC (N = 172), and IM 400 mg + PegIFN-α2a (N = 221) arms, respectively. The rate of major molecular response at 12 months and deep molecular response (MR4) over time were significantly higher with the combination IM 400 mg + PegIFN-α2a than with IM 400 mg: p = 0.0001 and p = 0.0035, respectively. Progression to advanced phases and secondary malignancies were the most frequent causes of death. Toxicity was the main reason for stopping AraC or PegIFN-α2a treatment.

In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.

Omega zeolite was synthesized by a hydrothermal method and then modified by ionic exchange using Na, Ca, K, Mg, Co and Cu cations. Analyses through CO2- and H2O-TPD revealed an improvement of the Lewis basicity as compared to the parent zeolite. CO2 adsorption was found to take place on two types of sites: i. strong sites on lattice oxygen located in 12- and 8-ring channels; ii. medium and weak sites located in 12-ring channels involving mainly silanol groups and adsorbed water. Weak Bronsted acidity and high porosity of alkali-exchanged Omega turned out to be essential requirements for high catalytic activity. Such catalysts exhibit heterogeneous charge dispersion but with beneficial effect for catalysis. The lowest conversion yields were registered with reagents bearing high electron density chlorine and/or nitro-groups, which may hinder adsorption at room temperature. MCR processes on Omega turned out to be governed by acid-base interactions between the reactants and zeolite surface.

The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. The median overall follow-up of the patients was 13.5 years (range 3 months to 16.7 years). Based on intention-to-treat analyses, at 15 years, overall and progression-free survival were similar across arms: 85%, 83%, 80%, and 82% and 84%, 87%, 79%, and 79% for the IM 400 mg (N = 223), IM 600 mg (N = 171), IM 400 mg + AraC (N = 172), and IM 400 mg + PegIFN-α2a (N = 221) arms, respectively. The rate of major molecular response at 12 months and deep molecular response (MR4) over time were significantly higher with the combination IM 400 mg + PegIFN-α2a than with IM 400 mg: p = 0.0001 and p = 0.0035, respectively. Progression to advanced phases and secondary malignancies were the most frequent causes of death. Toxicity was the main reason for stopping AraC or PegIFN-α2a treatment.

Three mesoporous silica, SBA-16, SBA-15 and MCM-41, with different structures and porosities were synthesized via a hydrothermal method and their interactions with carbon dioxide (CO2) were investigated through thermal programmed desorption (TPD) and differential scanning calorimetry. TPD measurements provided precise assessments of the intrinsic affinity towards CO2, without the influence of moisture. All silica materials were found to exhibit intrinsic affinity towards carbon dioxide, but the surface basicity, expressed in terms of retained CO2 amount, is markedly influenced by increases in pore size and framework structures. SBA-15 displayed the highest CRC values, explained in terms of larger pore size, lower numbers of acidic out-of plane Si–OH and higher numbers of much less acidic in-plane silanols. These findings provide valuable information for a better understanding of the role of the silica structure in the intrinsic basicity, prior to further modifications for improving the affinity towards CO2 or merely for catalysis purposes involving CO2 as reagents, intermediates or products.

Objective: The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. Methods: Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed. Results: According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01). Conclusion: We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm3 that must be taken into account when considering a CCR5 antagonist therapy switch.

The basicity of MCM-48-like silica and modified counterparts was investigated by CO 2 thermal programmed desorption (TPD) and differential scanning calorimetry (DSC). Post-synthesis modifications were achieved through: (i) incorporation of dihexylamine (DHA); (ii) DHA removal by ethanol; (iii) calcination at 550 °C in air stream and (iv) incorporation of Boltorn H-20 dendrimer. After DHA incorporation, the specific surface area dropped from 953 down to 74 m 2 g −1 , and the pore volume decreased from 0.41 to 0.13 cm 3 g −1 . The surface basicity, expressed in terms of retained CO 2 amount decreased markedly after template removal, but was slightly revived after dendrimer loading. CO 2 was found to adsorb via physical or chemical interactions on two types of sites, according to the post-synthesis treatment. Correlating TPD and DSC measurements allows assessing the extent of the acidity attenuation and basicity adjustment for a wide variety of catalysts and adsorbents through suitable post-synthesis modifications.

The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network. All patients who met the recent criteria of hypereosinophilia (HE) or HES and who had a persistent CD3-CD4+ T-cell subset on blood T-cell phenotyping were included. Clinical and laboratory data were retrospectively collected by chart review. CD3-CD4+ L-HES was diagnosed in 21 patients (13 females, median age 42 years [range, 5-75 yr]). Half (48%) had a history of atopic manifestations. Clinical manifestations were dermatologic (81%), superficial adenopathy (62%), rheumatologic (29%), gastrointestinal (24%), pulmonary (19%), neurologic (10%), and cardiovascular (5%). The median absolute CD3-CD4+ T-cell count was 0.35 G/L (range, 0.01-28.3), with a clonal TCRγδ rearrangement in 76% of patients. The mean follow-up duration after HES diagnosis was 6.9 ± 5.1 years. All patients treated with oral corticosteroids (CS) (n = 18) obtained remission, but 16 required CS-sparing treatments. One patient had a T-cell lymphoma 8 years after diagnosis, and 3 deaths occurred during follow-up.In conclusion, clinical manifestations related to CD3-CD4+ T cell-associated L-HES are not limited to skin, and can involve all tissue or organs affected in other types of HE. Contrary to FIP1L1-PDGFRA chronic eosinophilic leukemia patients, CS are always effective in these patients, but CS-sparing treatments are frequently needed. The occurrence of T-cell lymphoma, although rare in our cohort, remains a major concern during follow-up.

Introduction: Hairy-cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with a favorable outcome thanks to treatment with purine analogues (PNA) like cladribine and pentostatin. Here, we updated the French national retrospective cohort of HCL after 10 years of follow-up, in order to evaluate the risk of second cancers in these patients. Methods: Data were collected up to June 2018 through a questionnaire sent to the members of the Société Française d'Hématologie, and centralized in the cohort database. We described the second malignancies observed during the follow-up, distinguishing second 'solid' cancers from second hematological malignancies. Then, using a Fine and Gray model, we performed a multivariate analysis in order to identify second cancer risk factors. Finally, to evaluate the excess of cancers in our cohort in comparison with the French general population, we calculated the standardized incidence ratio (SIR). Results: 279 patients (pts) from 19 centers were included in our retrospective cohort. The median age was 59 years old (range 29-88). 21% had an infectious disease at diagnosis, 23% had a familial history of cancer and 11% a personal history of cancer before HCL diagnosis. The median number of lines of treatments was 1 (0-7). PNA (cladribine or pentostatin) were the first therapeutic choice in frontline (75% of pts) and at relapse (69%). With a median follow-up of 127 months (2-413), the median overall survival for the overall study population was 328 months (95% CI 299-357) and the median relapse-free survival (RFS) was 136 months (95% CI 109-163). Pts treated with cladribine or pentostatin in first line had a statistically significant better RFS than pts treated with 'other' treatments (log rank test, p < 0.001). The 10-year cumulative incidence of relapse was 39% (95% CI 33-46). Pts who received treatments other than PNA in first line had a higher risk of relapse (Gray's test, p < 0.001). For pts receiving PNA in first and second lines, there was no difference in outcomes between those who switched PNA and those who did not. In this cohort, we observed 68 second malignancies during the follow-up: 49 solid cancers (most prevalent: prostate and non-melanoma skin cancers) and 19 hematological malignancies (most prevalent: monoclonal gammopathy of undetermined significance (MGUS) and myelodysplastic syndromes (MDS)). The median onset of second cancer, second solid cancer and second hematological malignancy from HCL diagnosis was 81 months, 99 months and 78 months, respectively. The median age at diagnosis of cancer, solid cancer and hematological malignancy was 70, 69 and 77 years old, respectively. Considering death as a competing risk, the 10-year cumulative incidence of cancer, solid cancer and hematological malignancy was 15% (95% CI 11-19), 11% (95% CI 7.2-15), and 5.0% (95% CI 2.8-8.2), respectively. In multivariate analyses, IFN treatment was associated with a decreased risk for all cancers (Fine and Gray regression model, subdistribution Hazard Ratio (sdHR) 0.53 (95% CI 0.29-0.97); p = 0.038), a familial history of cancer was a risk factor for solid cancers (sdHR 2.12 (95% CI 1.15-3.91); p = 0.017), a personal history of cancer was a risk factor for hematological malignancies (sdHR 3.47 (95% CI 1.14-10.55); p = 0.028). Even after excluding non-melanoma skin cancers and MGUS, there was an excess of cancers (SIR = 2.22), solid cancers (SIR = 1.81) and hematological malignancies (SIR = 6.67). Conclusions: In this updated real-world retrospective cohort with a long follow-up and most pts treated with PNA, we highlighted the importance and the excess of second cancers in HCL patients, in particular hematological malignancies. Figure Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Hermine:AB Science: Membership on an entity's Board of Directors or advisory committees. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Troussard:Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Research Support; Sysmex: Other: Research Support.

Three polyglycerol dendrimers with average molecular weights of 500, 1100, and 1700 were obtained starting from glycidol derived from soybean oil. Intercalation of Na-montmorillonite with these dendrimers produced effective organo-Mt adsorbents (NaMt-500, NaMt-1100 and NaMt-1700, respectively) for the reversible capture of CO2. The CO2 retention capacity ( Q CO 2 ) was assessed through temperature-programmed desorption (TPD), and was found to increase with the number of OH groups incorporated. The latter turned out to be the main adsorption sites. Paradoxically, high dendrimer loadings and larger dendrimer generation did not necessarily raise the amount of adsorbed CO2, because of the formation of dendrimer clusters, which significantly reduces the number of accessible OH groups. The highest Q CO 2 values were registered for NaMt-1700 (3.88–7.14), NaMt-1100-1 (5.24) and NaMt-500 (11.70–16.42 μmol g−1) at loading grades. Such adsorbents can release CO2 at much lower temperatures as compared to amines and other base-like compounds, and turn out to be more suitable for CO2 concentration from major emission sources prior to sequestration or uses in chemical or biological processes. This opens new prospects for the preparation of effective CO2 adsorbents starting from low-cost and ecofriendly materials like clay minerals and hyperbranched polyalcohols deriving from vegetal oils.

Na-montmorillonite modification by the incorporation of hyperbranched polyglycerol dendrimers with average molecular weight 500, 1100 and 1700 g/mol and derived from soybean oil resulted in hybrid matrices with improved hydrophilic character and affinity toward carbon dioxide. Thermal analyses and thermal programmed desorption revealed that the dendrimer incorporation improved the amount of adsorbed water. The hydration grade was found to be proportional to the number of OH groups incorporated, and can double with the insertion of polyglycerol 500, 100 and 1700 at low dendrimer loadings. Inversely, higher dendrimer contents appeared to affect the hydrophilic character, favoring dendrimer aggregation into dense clusters, which reduces the number of OH groups accessible. This phenomenon was more accentuated with larger dendrimers. FTIR investigations also demonstrated that polyglycerol-based organoclays display improved interactions with water and/or carbon dioxide as compared to the starting material. The amount of adsorbed water was found to correlate with that of carbon dioxide, suggesting a certain contribution in CO 2 retention.

Polyalcohol incorporation was found to enhance the hydrophilic character of montmorillonite and its affinity towards carbon dioxide. CO2 adsorption occurred in both dry and humid conditions, but higher amounts were retained in the presence of moisture. This suggests two adsorption pathways: 1. direct OH-CO2 interaction and 2. more predominantly via indirect ternary OH-H2O-CO2 interactions. The retained amounts of water and CO2 increased almost proportionally with the number of OH groups incorporated, thus providing clear evidence that these groups act as adsorption sites. The improvement of the CO2 retention capacity (CRC) appears to be also due to the enhancement of the hydrophilic character of the adsorbent. The CRC value was found to strongly depend on the operating conditions. The major part of the retained CO2 was desorbed at 60-70°C from hydrated matrices, but at 20-50°C from dry adsorbents. CO2 can be easily released even at room temperature through forced convection under a gas stream, or under static conditions in dry and CO2-free media, e.g. in the presence of KOH pellets. It results that the CO2 retention also involves physical interactions. These results open new prospects for the reversible capture of other gases on low-cost hybrid adsorbents without thermal regeneration.

Carbon dioxide (CO2) was reversibly trapped using low cost hybrid matrices obtained through a mere incorporation of organic molecules bearing terminal hydroxyl groups in Na-montmorillonite. For this purpose various organic compounds ranging from bulky Boltorn dendrimers to light molecules like ethylene–glycol were used. At low loadings, the adsorption capacity increased almost proportionally with the number of OH groups. The latter acted as the main adsorption sites. Dendrimer contents exceeding 3 wt.% were found to enhance the hydrophobic character of the organic moiety, which aggregates into clusters and reduces the number of accessible sites. Unlike amine-based adsorbents, such matrices displayed weak interaction with CO2, but sufficient adsorption sites to satisfactorily retain CO2. The latter was contacted with adsorbent powder (0.01–0.1 mm particle size) at room temperature and normal pressure in the presence of nitrogen. Consecutive measurements through thermal programmed desorption gave CO2 retention capacity (CRC) values in the range 2–14 μmol g−1, expressed in terms of CO2 amount desorbed between 20 °C and 200 °C under a nitrogen throughput of 1–15 mL/min. The CRC value was found to be strongly depending on the structure of the incorporated organic molecule and the nitrogen flow rate during impregnation and saturation by CO2 and purge. Increasing the N2 flow rate was found to reduce the CRC value, due to CO2 removal by forced convection. The major part of CO2 can be released at temperature not exceeding 40–70 °C or even at room temperature upon exposure to strong nitrogen stream or in CO2-free media. This provides clear evidence of a truly reversible retention of CO2, and opens new prospects for ideal clay-based respiratory membranes bearing other chemical groups, capable to release the adsorbed gas through mere convection by a carrier gas stream, without heating.

Dendrimers bearing hydroxyl groups supported by layered double hydroxides (CO3–LDH) with Mg/Al ratio ranging from 1:1 to 5:1 showed improved properties for the reversible capture of carbon dioxide (CO2). The adsorption capacity of the starting LDH was due to the intrinsic base-like behavior, and was found to depend on the Mg/Al ratio. When contacted with polyol dendrimers in aqueous media, no intercalation took place. This was explained in terms of low exfoliation grade of LDH and hydrophobic character of the dendrimer molecules. The latter rather adsorb on the external surface of the LDH stacks for low dendrimer loadings, or aggregate into organic clusters for higher contents. Analyses through thermal programmed desorption of CO2 revealed that dendrimer incorporation advantageously attenuates the basicity strength of the starting LDH support, by lowering the desorption temperature. The OH groups of the organic moiety were found to display an amphoteric character, and act as the main adsorption sites. The weak interactions with CO2 facilitate easier release of the major part of adsorbed CO2 at temperature not exceeding 80–100 °C. On polyol organo-LDHs, the reversible CO2 retention was discussed herein in terms of acid–base interactions. This concept allows envisaging the capture of diverse pollutants and other greenhouse gases by modifying the chemical groups on the dendritic moiety.

This paper focuses on the synthesis of polyol/MCM-48 nanocomposite materials with different percentage of polyalcohol dendrimer H20. The obtained materials have been used for CO2 adsorption. CO2-TPD analysis shows that the samples containing 1 and 3 wt% of H20 dendrimer have low CO2 adsorption capacity due to the occupation of active site, while the sample prepared by 0.5 wt% of H20 dendrimer, exhibit higher adsorption capacity and thermal stability although the adsorption capacity decreased with increasing molecular weight of dendrimer. The affinity towards CO2 was found to be mainly to the presence of organic moiety within the MCM-48 pores.

To assess real-life treatment practices with imatinib for chronic-phase chronic myeloid leukaemia (CP-CML) in France.In the observational 'Unmet Needs in CML' (UNIC) study of CML management in Europe, case report forms were completed retrospectively for eligible patients (or =18 years of age, currently treated for CML) during enrolment (September 2006-March 2007). Results from the subset of patients from France are presented.Primary objectives were to estimate from the collected data the proportions of patients ever treated with imatinib and those experiencing imatinib resistance and/or intolerance as determined by physicians' diagnoses of resistance/intolerance leading to a change in imatinib use. Collected data were analysed descriptively. Secondary descriptive measures included imatinib dose modifications and methods for treatment response monitoring.Of the 654 French CP-CML patients, 95.9% had received imatinib. Of these, 15% were judged by physicians as imatinib-resistant and 31% as imatinib-intolerant (not mutually exclusive) during treatment, 44% required dose modification and 23% discontinued imatinib. In the 12 months preceding the last observation, 65% had a cytogenetic features analysis and 93% had a polymerase chain reaction (PCR) assessment of molecular response. Importantly, and contrasting with European recommendations, 46% of imatinib-resistant patients had never been assessed for BCR-ABL mutations.The observational study design limits data collection and interpretation. The findings are specific to the French healthcare system and may not apply to other countries.This observational study of CP-CML management in France confirmed that most patients are treated with imatinib, a treatment widely recognised as efficacious. The study highlights opportunities for optimising CML management, as a proportion of patients may require alternative treatment strategies due to imatinib resistance/intolerance. Response monitoring rates differ from recommendations, representing another opportunity for improving care for CP-CML patients through early identification of patients failing current therapy.

The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome. Atypical CD4(+) T cells lymphoid infiltrates were found in 10 of 12 CD3(-)CD4(+) L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3(-)CD4(+) T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3(-)CD4(+) T cells were CD2(hi) (n=9 of 14), CD5(hi) (n=12 of 14), and CD7(-)(n=4 of 14) or CD7(low) (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3(-)CD4(+) T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative disorder, which should not be confused with angio-immunoblastic T-cell lymphoma.

The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients.Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed.According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p0.0001) and loss of an N-linked glycosylation site (p0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01).We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when considering a CCR5 antagonist therapy switch.

We report the clinical response and biological effects of treatment with rituximab and fludarabine (RF) in five patients with IgM anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy. Between November 2006 and October 2009, four men and one woman aged 52-85 years received intravenous rituximab at 375 mg/m(2) on day 1 and oral fludarabine at 40 mg/m(2) /day from days 1 to 5, in a treatment cycle that was repeated every month for up to 6 months. Two patients had IgM monoclonal gammopathy of undetermined significance and three low tumor mass Waldenstrom's macroglobulinemia. Four patients showed a major hematological response with a decrease in anti-MAG titer in three and clearing in one. One patient did not respond. For the responding patients, symptoms and electrophysiological parameters improved significantly. No patient relapsed at post-RF treatment follow-up (12-45 months), and no toxicity was reported. The combination of RF induced significant responses in IgM anti-MAG demyelinating neuropathies, without toxicity. Clinical improvements were correlated to hematological and immunological results.

Objectives: This study aimed to provide further clinical evidence for the efficacy and safety of epoetin β once weekly across a wide range of cancer types. Methods: This was a multicenter, open-label, prospective, single-arm study in patients with either a solid tumor or non-myeloid hematological malignancy, receiving or scheduled to receive further chemotherapy. Patients received epoetin β 30,000 IU subcutaneously once weekly for 16 weeks. The primary efficacy endpoint was the change in hemoglobin (Hb) level according to the patient’s baseline Hb level. Results: A total of 691 patients were included in the intent-to-treat population. Epoetin β effectively increased Hb levels (a mean increase from baseline of 1.1 g/dl by week 4 and 2.2 g/dl by week 12). Hb response was achieved in 60.4% of all patients and 61.2% of those with baseline Hb Conclusions: Epoetin β 30,000 IU once weekly effectively increases Hb levels, is well tolerated and has similar efficacy in anemic patients with solid tumors or non-myeloid hematological malignancies.

e20520 Background: Comprehensive geriatric assessment (CGA) helps therapeutic decision, predicts chemotherapy toxicities and early deaths in elderly patients treated for advanced cancer. CGA, perfo...

In non-randomized studies, thalidomide appeared to be effective in myeloid metaplasia with myelofibrosis (MMM). We compared thalidomide to placebo for treatment of anemia in MMM.A prospective phase II B, randomized double-blind multicenter trial comparing thalidomide 400 mg/d with placebo for 180 days was conducted in 52 anemic patients (hemoglobin pounds Sterling 9 g/dL or transfused). The main outcome measure was a 2 g/L increase in hemoglobin or 20% reduction in transfusions.In the thalidomide group only 10 patients completed 6 months of treatment. At 180 days, in an intention-to-treat analysis, no difference was observed between the thalidomide and placebo groups as regards improvement of hemoglobin levels (one patient in each group) or reduction of red blood cell transfusions (three vs five patients, respectively). The spleen size, determined by ultrasonography, increased significantly less in the thalidomide group than in the placebo group (p0.05). Thalidomide had no apparent benefit on the Dupriez score, the severity score, survival, death, or any other clinical or biological parameter. Somnolence, gastro-intestinal signs, weight gain, and edema were significantly more frequent in the thalidomide group. Outpatient discontinuation of thalidomide was significantly correlated with a high severity score4 (odds ratio, OR = 16; p0.01), and g-glutamyl transferase levels40 IU/L (OR = 12; p0.05).Thalidomide (200-400 mg/d) does not demonstrate substantial efficacy in anemic MMM patients. The natural history of disease in the placebo group revealed spontaneous periods of remission of anemia. Tolerance of thalidomide was significantly correlated wih the severity and liver involvement of the disease.

V617F JAK2 mutation is a reliable molecular marker of polycythemia vera (PV), potentially useful to monitor the effect of treatments in this disease. In a phase 2 study of pegylated (peg) IFN-alpha-2a in PV, we performed prospective sequential quantitative evaluation of the percentage of mutated JAK2 allele (%V617F) by real-time polymerase chain reaction (PCR). The %V617F decreased in 24 (89%) of 27 treated patients, from a mean of 49% to a mean of 27% (mean decrease of 44%; P < .001), and no evidence for a plateau was observed. In one patient, mutant JAK2 was no longer detectable after 12 months. In 3 patients homozygous for the mutation, reappearance of 50% of wild-type allele was observed during treatment. The results seem to confirm the hypothesis that IFN-alpha preferentially targets the malignant clone in PV and show that %V617F assessment using a quantitative method may provide the first tool to monitor minimal residual disease in PV. This trial was registered at www.clinicaltrials.gov as #NCT00241241.

Abstract 280 Background: Two phase 2 studies have recently shown promising results of peg-IFNα-2a therapy in PV and essential thrombocythemia, including major efficacy, satisfactory tolerance, and significant molecular responses, renewing the interest for IFNα therapy in patients (pts) with MPN. However, no prospective study has assessed the long-term safety and efficacy of IFN therapy in those pts. We analyzed the long-term results of the PVN1 trial (www.clinicaltrials.gov #NCT00241241), a phase 2 study of peg-IFNα-2a therapy in PV, after a median follow-up (FU) of 6.4 years. Patients and methods: 40 PV pts were enrolled in the study between Sept 04 and Sept 05. 4 pts were not evaluable (1 inclusion criteria violation, 2 withdraws of consent, 1 allergic reaction at first injection). Median age was 50 yrs (range 22–65). Median time since diagnosis was 6 months (range 1–65). 9 pts (25%) had previously received hydroxyurea. 6 pts (17%) had a history of thrombosis. 7 pts (20%) had splenomegaly. Long-term analyses were performed in 34 patients in June 11 (2 pts lost to FU). Hematological, molecular and histological responses were assessed according to the European LeukemiaNet (ELN) criteria. Results: Median FU was 77.4 months (mos) (Q1−Q3: 72 – 81 mos) and median duration of peg-IFNα-2a therapy was 47.4 mos (Q1-Q3: 28 – 77 mos). Clinical-hematological efficacy: At last evaluation, 32/34 pts (94%) were in hematological response including 28/34 complete responses (CR) (82%) and 4 partial responses (PR), and 2 pts had relapsed. 14 pts (41%) were still treated with peg-IFNα-2a for a median time of 70 mos. During FU, 20 pts stopped IFN after having received the drug for a median time of 42 mos. Among them, 10 pts (29% of the total cohort) had stopped because of sustained hematological CR, 8 (23%) because of toxicity, and 2 (6%) at investigator's discretion. 13 (38% of the total cohort) of the 20 pts who stopped therapy did not received any other cytoreductive treatment after peg-IFNα-2a discontinuation, and 10/13 were still in hematological CR off-therapy at last evaluation after a mean observation period of 28+ mos (range 3+ – 64+ mos). During FU, PV relapsed in 3/13 pts who had stopped cytoreductive therapy after a mean time of 25 mos (range 6 – 37 mos). Peg-IFNα-2a was restarted in 2 of them and a second hematological CR was achieved. None of the patients experienced any vascular event during FU, when about 10 events would have been expected in this series of 34 PV pts followed for 77 mos (5.5% pts/year in the ECLAP study). Molecular and histological responses: Molecular response was assessed by measuring JAK2V617F allele burden in granulocytes (%V617F) in 29 pts with serial samples: a molecular response was achieved in 24 pts (83%) including 8 molecular CR (28%), and only 5 pts (17%) had no decrease in their %V617F. Mean %V617F was 47% (range 10 – 100%) at baseline, and 10% (range 0 – 45%) at 72 mos. 4 pts had a TET2 mutation: in none of them the TET2 mutant allele burden decreased during therapy although median decrease in %V617F in the same samples was 100% (Q1 – Q3: 75% – 100%). Bone marrow biopsies performed in some pts in hematological CR after discontinuation of peg-IFNα-2a found a normalized BM morphology fulfilling the ELN criteria for histological CR, and excluded an evolution to myelofibrosis as a cause for “apparent” remission. Toxicity: Peg-IFNα-2a was stopped because of adverse event in 8 pts (23%): fatigue in 2, depression in 1, grade 2 neuropathy in 1, arthralgia in 1, thyroiditis in 1, auto-antibodies in 1, liver enzyme elevation in 1 pt, respectively. Importantly, no unexpected adverse event was observed in spite of the very long-term use of peg-IFNα-2a (median of 45.5 mos). Conclusion: In this prospective phase 2 study of PV pts treated with peg-IFNα-2a after 6.4 years median FU, we recognized that: 1) 94% of pts were still in hematological response, including 82% CR; 2) 29% of pts could stop peg-IFNα-2a and remained in hematological response without further cytoreductive therapy after a median observation time of 28+ mos (up to 64+ mos); 3) major and sustained molecular response in %V617F was confirmed in 83% of patients, including 28% who achieved complete molecular response, while TET2 mutated clones appeared resistant to peg-IFNα-2a; 4) histological CR was also achieved in selected patients; 5) no vascular event was observed after 6.4 years median FU; 6) no new safety concern arose with prolonged utilization of peg-IFN alpha-2a. Disclosures: Off Label Use: Phase 2 study of pegylated-Interferon alpha-2a in polycythemia vera (off-label).

Background: Epidemiological data on MDS is scarce in France, and registries from other countries do not provide data on the daily practice management of MDS in 2008. Methods: GFM centers were asked to collect characteristics of ongoing or recent treatments in all MDS patients (pts) seen at their clinic (as in or outpatients) during the Jan 28th–Feb 3rd, 2008 period (one week).Results: 919 pts from 74 centers were included, 57% males, mean age (+/− SD), 73 (±11) years, with 2.8%, 19% and 28% of pts aged 80 years, respectively (resp).13% of pts were hospitalized >24h (4.5% for infections or bleeding and 8.5 % for “active” treatments), 46% were seen in the day care facility (40% for transfusions), and 41% as consultations (for staging, follow up or ambulatory treatment). 93% of patients had PS ≤2. Median interval from diagnosis to survey was 29.2 months. FAB at time of survey was: 35.1% RA, 18.5% RARS, 39.1% RAEB, 7.4% CMML; WHO was: 17.4% RA, 13.3% RARS, 14% RCMD, 4.5% RCMD-RS, 18.5% RAEB-1, 15.9% RAEB-2, 7.7% CMML, 4.9% 5q-syndrome and 3.9% unclassifiable. Cytogenetic analysis had been performed at least once in 77.4 % pts: favorable (498 pts), intermediate (88 pts), unfavorable (96 pts). IPSS (determined in 75.4% of pts) was: 41.6% low, 33.3% Int-1, 16.4% Int-2 and 8.7% high. Significant differences between pts 65 years were, respectively, % of unfav karyotype (25.8% vs. 12.7%, p=0.0004), of isolated +8 (5.1% vs. 2.1%, p=0.04), of isolated −7 (6.2% vs. 1.1%, p=0.0003), and, with borderline significance, of CMML (4.5% vs. 9.5%, p=0.06), of 5q-syndrome (1.5% vs. 5%, p=0.07). EPO level, assessed in 359 (39.1%) of pts at diagnosis and 252 (27.4%) of pts at time of survey) was >200UI/l in 24.5% and 26.6% resp, and >500U/l in 13.5% and 14.7% pts resp and was significantly correlated with interval from diagnosis. At the time of survey, treatment received in the last 6 months (IPSS: high-int 2 vs low–int1) included: no active treatment 66.5% (IPSS: 42% vs. 72.9%), chemotherapy 12.8% (IPSS: 22.6% vs. 9.1%) including 2.7% intensive and 0.7% LD AraC, allogeneic SCT 1.7% (IPSS: 3.8% vs. 2.6 %) including 0.3% classical and 1.4% NMA, azacytidine 6.5%, (IPSS: 21.6% vs. 2.3%), decitabine 0.8%, lenalidomide 4%, thalidomide 0.5%, ATG 0.2 %, androgens 2.2% while 64.8% pts required RBC transfusions (IPSS: 81% vs. 61%) and 39.7% pts received an Erythropoiesis-Stimulating Agent (ESA) (IPSS: 40.3% vs. 37.2%), alone in 314 pts (epoetin alfa or beta in 92 pts, darbepoetin in 222 pts), and with G-CSF (61 pts). Response rates to ESAs were 58.6% and 33.8% in low int-1 and int-2-high risk MDS, resp (p=0.0009). Iron chelation therapy was administered in 17.6% pts (5.8% desferroxamine, 11% deferasirox) including 22.1% and 13.6% low-int-1 and int-2-high risk MDS, resp (p=0.009). Conclusions: Our survey provides a better knowledge of the characteristics and of the daily management of MDS in France. Of particular note are the more frequent unfavorable karyotypes in MDS pts