High-risk additional chromosomal abnormalities at low blast counts herald death by CML

Blast crisis is one of the remaining challenges in chronic myeloid leukemia (CML). Whether additional chromosomal abnormalities (ACAs) enable an earlier recognition of imminent blastic proliferation and a timelier change of treatment is unknown. One thousand five hundred and ten imatinib-treated patients with Philadelphia-chromosome-positive (Ph+) CML randomized in CML-study IV were analyzed for ACA/Ph+ and blast increase. By impact on survival, ACAs were grouped into high risk (+8, +Ph, i(17q), +17, +19, +21, 3q26.2, 11q23, -7/7q abnormalities; complex) and low risk (all other). The presence of high- and low-risk ACAs was linked to six cohorts with different blast levels (1%, 5%, 10%, 15%, 20%, and 30%) in a Cox model. One hundred and twenty-three patients displayed ACA/Ph+ (8.1%), 91 were high risk. At low blast levels (1-15%), high-risk ACA showed an increased hazard to die compared to no ACA (ratios: 3.65 in blood; 6.12 in marrow) in contrast to low-risk ACA. No effect was observed at blast levels of 20-30%. Sixty-three patients with high-risk ACA (69%) died (n = 37) or were alive after progression or progression-related transplantation (n = 26). High-risk ACA at low blast counts identify end-phase CML earlier than current diagnostic systems. Mortality was lower with earlier treatment. Cytogenetic monitoring is indicated when signs of progression surface or response to therapy is unsatisfactory

Hemispheric differences in the duration of focal onset seizures

OBJECTIVE To assess hemispheric differences in the duration of focal onset seizures and its association with clinical and demographic factors. METHODS A retrospective analysis was performed on adult patients with drug-resistant unifocal epilepsy, who underwent intracranial EEG recording between 01/2006 and 06/2016. Seizure duration was determined based on the subdural and/or stereo-EEG (sEEG) recordings. Hemispheric differences in seizure duration were statistically evaluated with regard to clinical and demographic data. RESULTS In total, 69 patients and 654 focal onset seizures were included. The duration of seizures with left-hemispheric onset (n~=~297) was by trend longer (91.88~±~93.92~s) than of right-hemispheric seizures (n~=~357; 71.03~±~68.53~s; p~=~.193). Significant hemispheric differences in seizures duration were found in temporal lobe seizures (n~=~225; p~=~.013), especially those with automotor manifestation (n~=~156; p~=~.045). A prolonged duration was also found for left-hemispheric onset seizures with secondary generalized commencing during waking state (n~=~225; p~=~.034), but not during sleep. A similar hemispheric difference in seizure duration was found in female patients (p~=~.040), but not in men. CONCLUSIONS Hemispheric differences in seizure duration were revealed with significantly longer durations in case of left-hemispheric seizure onset. The observed differences in seizure duration might result from brain asymmetry and add new aspects to the understanding of seizure propagation and termination

Iron Chelation in Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms—Real-World Data from the German Noninterventional Study EXCALIBUR

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing the requirement for RBC transfusions. To assess the utility, efficacy, and safety of the different iron chelation medications approved in Germany, as well as to examine the effect of chelation on hematopoietic insufficiency, a prospective, multicenter, noninterventional study named EXCALIBUR was designed. In total, 502 patients from 106 German hospitals and medical practices were enrolled. A large proportion of patients switched from a deferasirox dispersible tablet to a deferasirox-film-coated tablet, mainly because of more convenient application, which was reflected in the treatment satisfaction questionnaire for medication scores. Iron chelation was effective in lowering serum ferritin levels, with the observed adverse drug reactions being in line with the known safety profile. Hematologic response occurred in a few patients, comparable to other studies that examined hematologic improvement in patients with MDS

Who seizes longest? Impact of clinical and demographic factors

Objective To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from intracranial electroencephalographic (iEEG) recordings. Methods Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006‐2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports. Results In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic‐clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS‐BTCs; 556/654, P < .001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P = .003) and was significantly shortened (P < .001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P = .015) and sign of four (P = .043) were associated with longer bilateral tonic‐clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P < .001) and disease duration (P = .028) were essential for prediction of FS‐BTC duration, whereas the vigilance state (P = .085) was the main prediction factor for the duration of FBTCSs. Significance The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures

Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS

OBJECTIVE As peripheral blood (PB) Wilm's Tumor 1 (WT1)-mRNA expression is established as MRD-marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post-transplant outcome in patients with AML/MDS. METHODS In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut-off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post-transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse-free (RFS), and overall survival (OS). RESULTS Pretransplant forty-six patients (72%) showed hematologic remission, including 21 (46%) MRD-negative and 25 (54%) MRD-positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two-year estimates of post-transplant CIR, RFS, and OS were similar in MRD-positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD-negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P~=~.008), RFS (P~=~.005), and OS (P~=~.049). CONCLUSIONS PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post-transplant outcome and may help improving peri-transplant management in AML/MDS patients

Influence of platelet count at diagnosis and during the course of disease on prognosis in MDS patients

Thrombocytopenia at diagnosis and platelet drop within the first 6~months have an adverse effect on prognosis of MDS patients. We therefore were interested in the association and impact on prognosis of morphologic findings of megakaryocytes and platelets with platelet count at diagnosis, bleeding complications, and the drop of platelets during the course of disease. This retrospective analysis was based on 334 MDS patients from the Duesseldorf MDS registry that were followed up for blood counts, bleeding, transfusion dependency, and AML evolution and correlated with morphology of the megakaryocytes and platelets. Thrombocytopenia was found more frequently in higher risk MDS and was associated with hypocellularity of the megakaryocytes in the bone marrow. Signs of bleeding were present at diagnosis in 14% and occurred during the disease in 48% of all MDS patients. Death due to bleeding was ranked third behind infections and AML. A decrement of platelets during the first 6~months was associated with an inferior overall survival of 21 vs. 49~months and with a higher cumulative 2-year AML rate of 22.2% vs. 8.3% (p = 0.001). In a multivariate analysis, besides bone marrow blasts and karyotype, decreasing platelets were also associated with an inferior outcome. Signs of bleeding are present in a relevant number of MDS patients and account for significant morbidity and mortality in MDS. We could demonstrate the prognostic importance of decreasing platelets during the course of disease in all MDS patients, identifying patients at higher risk for death or AML progression

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence