MOG-Ab prevalence in optic neuritis and clinical predictive factors for diagnosis.

OBJECTIVE: What is the proportion of antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) in optic neuritis (ON) in adults and what would be the ON presentation for which MOG-Ab should be tested? METHODS: Multicentric prospective study conducted during 1 year on all patients diagnosed with acute ON in all ophthalmological units in hospitals in a region in western France. RESULTS: Sixty-five patients were included. MOG-Ab prevalence was 14% (9/65) during an acute ON and 13% (7/55) after exclusion of patients already diagnosed with multiple sclerosis (MS) (8) or MOG+ON (2). Compared with MS and clinically isolated syndrome, MOG+ON had no female preponderance (67% of men in case of MOG+ON and 22% of men in case of MS and clinically isolated syndrome, p<0.05) were more often bilateral (44% vs 3%, p<0.005) and associated with optic disc swelling (ODS) (78% vs 14%, p<0.001). To predict MOG+ON, the positive predictive values (PPVs) of male sex, ODS and bilateral involvement were 29% (95% CI 9% to 48%), 41% (95% CI 18% to 65%) and 40% (95% CI 10% to 70%), respectively, while the negative predictive values (NPV) were 93% (95% CI 86% to 100%), 96% (95% CI 90% to 100%) and 91% (95% CI 83% to 99%), respectively. The combined factor 'ODS or bilateral or recurrent ON' was the best compromise between PPV (31% (95% CI 14% to 48%)) and NPV (100% (95% CI 100% to 100%)). CONCLUSION: Among ON episodes, MOG-Ab were found in 14% of cases. MOG+ON occurred without female preponderance and was significantly associated with ODS and/or bilateral ON. Testing MOG-Ab only in patients presenting with ODS or bilateral or recurrent ON would limit MOG-Ab tests to fewer than half of all patients without the risk of missing any MOG+ON cases.

Reliability and reproducibility of disc-foveal angle measurements by non-mydriatic fundus photography.

PURPOSE: Abnormal torsion could be associated with cyclovertical strabismus, but torsion measurements are not reliable in children. To assess an objective fundus torsion evaluation in a paediatric population, we used Non-Mydriatic Fundus photography (NMFP) in healthy and cyclovertical strabismus patients to evaluate the disc-foveal angle over time and observers. METHODS: We used a retrospective set of NMFP including 24 A or V-pattern strabismus and 27 age-matched normal children (mean age 6.4 and 6.7 years respectively), taken during 2 distinct follow-up consultations (separated by 251 and 479 days respectively). Each disc-foveal angle measurement (from which the ocular torsion can be assessed) was performed by 5 different observers, using graphical software and based on reproducible fundus anatomical marks. Statistical analysis was performed with a multivariate ANOVA using group, time and observers as factors, in addition to intraclass coefficient correlation (ICC) to assess measurement reproducibility. RESULTS: A significant difference of disc-foveal angle measures was observed between groups (p<0,001): 18.73° (SD = 6.42), -3,25° (SD = 5.51) and 6,89° (SD = 4,41) respectively for V-pattern, A- pattern and normal subjects. Neither observers (F = 0,2028 p = 0,9369) nor time between 1st and 2nd NMFP (F = 0,6312 p = 0,4271) seem to influence the measure of disc-foveal angle. The evaluation of disc-foveal angle was very reproducible between observers (ICC>0,97). CONCLUSION: Abnormal amount of objective torsion could be associated with alphabet-pattern strabismus. Disc-foveal angle evaluation by NMFP in a children population appears as a non-invasive, reliable and reproducible method.

Treatment of Elderly Patients With Acute Myeloid Leukemia.

OPINION STATEMENT: There is no standard of care for older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy. AML in older patients remains an area of significant unmet need necessitating novel therapeutic strategies. In older patients with normal cytogenetics, molecular variables can be helpful in refining risk. This molecular revolution has promoted a shift in the treatment paradigm of AML. Open new questions concern the necessity of an individualized therapy that may take into account not only an increase in survival but also the maintenance or improvement in terms of quality of life, the management of symptoms, and a maximization of time outside of hospital care. Molecular abnormalities provide the genomic footprint for the development of targeted therapies. Clinical trials testing the activity of these new agents are ongoing and may reshape treatment strategies for these patients. One promising strategy is to combine low-intensity treatments with novel agents.

Acute myeloid leukemia in the elderly (age 70 yr or older): long-term survivors.

OBJECTIVE: Little data exist regarding long-term survival in elderly patients with acute myeloid leukemia (AML). METHODS: In view of the fact that most deaths occurred during the first 3 yr, this study examined long-term survival in this patient population, defined as overall survival for at least 3 yr with the aim to determine the number of long-term survivors and to identify factors that might impact on longer survival. RESULTS: The criterion for entry into this cohort was fulfilled by 57 patients among 302 seen over a 14-yr period (19%): 12 patients who never achieved complete remission (CR), 21 patients who relapsed after CR achievement, and 24 patients who achieved CR and did not relapse, including three patients who died while in CR and 21 patients still alive in first CR at the time of analysis. The pretreatment prognostic importance of cytogenetics was still apparent. However, some patients with secondary AML and/or unfavorable-risk markers belonged to long survivors. The cohort involved mainly patients treated by intensive chemotherapy, but also some patients receiving low-intensity therapies. CONCLUSION: Improved results should come from a better selection of patients to a more 'personalized' therapeutic approach combined with better supportive care assessment.

Treatment patterns and comparative effectiveness in elderly acute myeloid leukemia patients (age 70 years or older): the Lyon-university hospital experience.

The treatment of very elderly patients (≥70 years) with acute myeloid leukemia remains controversial. We present here 302 patients seen over a 14-year period in order to understand the real-world treatment patterns and outcomes in this patient population. Less than 25% of patients achieved a complete remission. The median overall survival was 12.4, 11.5 and 2.6 months, with a 3-year rates of 27%, 17% and 6%, for non-acute promyelocytic leukemia patients receiving intensive chemotherapy, lower-intensity therapy or best supportive care (BSC), respectively. In all ages, results were not significantly different among patients receiving low-intensity therapy and intensive chemotherapy, but significantly worse in those treated with BSC only. Similarly, intensive chemotherapy and low-intensity therapy gave better survival rates than BSC in patients with favorable- or intermediate-risk cytogenetics and in those with unfavorable cytogenetics (p < 0.0001 and p = 0.04, respectively).

Treating adults with acute lymphocytic leukemia: new pharmacotherapy options.

INTRODUCTION: Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outcome of salvage chemotherapy is very disappointing with less than 10% of long survival. Novel agents are therefore desperately required to improve response rates and survival, but also the quality of life of patients. Areas covered: The following review is a comprehensive summary of various novel options reported over the past few years in the therapeutic area of adult ALL. Expert opinion: Identifying key components involved in disease pathogenesis may lead to new approaches. In a near future, the incorporation of monoclonal antibodies and T-cell directed approaches including blinatumomab and chimeric antigen receptor T cells may increase the cure rates and may reduce the need for intensive therapy.

Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia.

Patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) and patients whose minimal residual disease persists during treatment have a poor leukemia-free survival. Despite improvements in front-line therapy, the outcome in these patients remains poor, especially after relapse. As there are no standard chemotherapeutic regimens for the treatment of patients with R/R B-precursor ALL, T-cell-based therapeutic approaches have recently come to the forefront in ALL therapy. Recently, monoclonal antibodies have been developed to target specific antigens expressed in B-lineage blast cells. In this setting, CD19 is of great interest as this antigen is expressed in B-lineage cells. Therefore, it has been selected as the target antigen for blinatumomab, a new bi-specific T-cell engager antibody. This sophisticated antibody binds sites for both CD19 and CD3, leading to T-cell proliferation and activation and B-cell apoptosis. Owing to its short serum half-life, blinatumomab has been administrated by continuous intravenous infusion with a favorable safety profile. The most significant toxicities were central nervous system events and the cytokine release syndrome. This new therapeutic approach using blinatumomab has been shown to be effective in patients with positive minimal residual disease and in patients with R/R B-precursor ALL leading to a recent approval by the US Food and Drug Administration after an accelerated review process. This review focuses on the profile of blinatumomab and its efficacy and safety.

The safety of treatment options for elderly people with acute myeloid leukemia.

INTRODUCTION: Life expectancy in elderly patients with acute myeloid leukemia (AML) is a function of age, disability, and co-morbidity, combined with leukemia characteristics. There is currently no consensus regarding the optimal therapeutic strategy for older adults with AML. Although selected older adults with AML can benefit from intensive therapies, recent evidence supports the use of lower-intensity therapies in most patients and emphasizes the importance of tolerability and quality of life. AREAS COVERED: Results of the current clinical trials and safety data are reviewed. EXPERT OPINION: Treatment recommendations for elderly patients with AML need to be individualized. In order to avoid toxicities, hematologists should collaborate more with geriatricians to identify clues of vulnerability in elderly patients through the study of functional physical, physiological, cognitive, social, and psychological parameters.

Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.

l-asparaginase, an enzyme originally derived from Escherichia coli, represents a major drug in the treatment of acute lymphoblastic leukemia. However, the occurrence of major adverse effects often leads to early withdrawal of the enzyme. Main side effects include immune-allergic reactions, coagulopathy, pancreatitis and hepatic disorders. Novel asparaginase formulations and alternative sources have been developed to address this issue, but the results were not totally satisfactory. l-asparaginase loaded red blood cells (RBCs; GRASPA) represent a new asparaginase presentation with reduced immunological adverse reactions. RBCs protect l-asparaginase, enhance its half-life and reduce the occurrence of adverse events. We reviewed the history, biology and clinical experiences with l-asparaginase, and the characteristics and first clinical experiences with GRASPA in the treatment of acute leukemia.

Antibody-based therapies in B-cell lineage acute lymphoblastic leukaemia.

Targeted therapies represent a major breakthrough in the treatment of adult acute lymphoblastic leukaemia (ALL). Because lymphoblastic leukaemia cells express a variety of specific antigens, those ones can serve as targets for monoclonal antibodies (MoAbs). Anti-CD20 (rituximab), anti-CD19 (blinatumomab, SAR3419), anti-CD22 (epratuzumab, inotuzumab ozogamicin) and anti-CD52 (alemtuzumab) have therefore been developed. Possible strategies even include recruitment of CD3 cytotoxic T cells (blinatumomab) or adoptive T-cell therapy by gene transfer of CD19-chimeric antigen receptors (CD19-CARs). Recent data show that antibody-based therapy is a highly promising treatment approach. However, optimal treatment approach still needs to be defined.

Initial absolute lymphocyte count as a prognostic factor for outcome in acute myeloid leukemia.

The absolute lymphocyte count (ALC) at presentation has been associated with survival in various malignancies. However, its prognostic value in acute myeloid leukemia (AML) has not been established. In a series of 1702 newly diagnosed patients with AML, we evaluated the prognostic value of ALC at diagnosis with regard to induction chemotherapy response, disease-free survival (DFS) and overall survival (OS). Low initial ALC (< 1 × 10(9)/L) appeared as a poor prognostic factor for DFS (p = 0.01) and OS (p = 0.02), while higher ALC (> 4.5 × 10(9)/L) showed a lower response rate after one (p = 0.004) or two induction chemotherapy courses (p = 0.01). However, ALC did not appear as an independent predictor of outcome in a multivariate analysis model also including age, cytogenetics and white blood cell count. Examination of lymphocyte subsets is warranted to specify the relationship between ALC at diagnosis and clinical outcome in AML.