Dinutuximab Beta Maintenance Therapy in Patients with High-Risk Neuroblastoma in First-Line and Refractory/Relapsed Settings-Real-World Data.

Dinutuximab beta is approved for the maintenance treatment of patients with high-risk neuroblastoma (HR-NB), including patients with relapsed/refractory (R/R) disease. However, the data on its use in real-world clinical practice is limited. We retrospectively reviewed the clinical records of 54 patients with HR-NB who received maintenance therapy with dinutuximab beta in first-line (37 patients) or R/R settings (17 patients) at three centers in Poland. Of the 37 patients who received first-line treatment, twenty-eight had a complete response, two had a partial response, three had progressive disease, and four relapsed at the end of treatment. The median overall survival (OS) was 24.37 months, and the three-year progression-free survival (PFS) and OS were 0.63 and 0.80, respectively. Of the 17 patients in the R/R group, 11 had a complete response, two had a partial response, one had stable disease, and three had progressive disease or relapsed at the end of treatment. The median OS was 33.1 months and the three-year PFS and OS were 0.75 and 0.86, respectively. Treatment was generally well tolerated, including in patients with co-morbidities and those who had experienced toxicities with previous therapies. These findings demonstrate that the use of dinutuximab beta is feasible and beneficial as a first-line or R/R treatment in routine clinical practice in Poland.

Assessment of chromosome stability in boars.

Chromosome instability adversely affects animal fertility and reproduction. Analysis of instability can be a valuable diagnostic tool. Helpful tests for assessment of instabilities include the sister chromatid exchange assay, identification of fragile sites, the bleomycin assay and the comet assay. These techniques can be used to assess and compare the chromosome stability of individual breeds of animals. The aim of the study was to assess chromosome stability in boars: Duroc, Duroc x Pietrain and Pietrain x Duroc crossbreds, Polish Large White, and the Neckar, P76 and PIC lines. The study assessed the chromosome stability of boars. The distribution of instabilities in individual breeds was varied. The average frequency of chromatid exchange was 4.8 ± 1.5, while that of fragile sites was 3.9 ± 1.4. The mean level of DNA damage (% tail DNA) was 9.4 ± 8.3, while in the bleomycin assay b/c and %AM were 0.6 ± 0.7 and 44.4 ± 4.1. A higher rate of instability was found in older individuals than in younger ones. The cytogenetic assays used to identify various forms of chromosome instability can be used to evaluate boars intended for breeding.

PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review.

It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

Up-regulation of stress-inducible genes in tobacco and Arabidopsis cells in response to abiotic stresses and ABA treatment correlates with dynamic changes in histone H3 and H4 modifications.

Animal cells react to mitogenic or stress stimuli by rapid up-regulation of immediate-early (IE) genes and a parallel increase in characteristic modifications of core histones: chromatin changes, collectively termed the nucleosomal response. With regard to plants little is known about the accompanying changes at the chromatin level. We have used tobacco BY-2 and Arabidopsis T87 cell lines to study the nucleosomal response of plant cells to high salinity, cold and exogenous abscisic acid (ABA). When in quiescent stage, both tobacco and Arabidopsis cells show the typical nucleosomal response to high salinity and cold stress, manifested by rapid transient up-regulation of histone H3 Ser-10 phosphorylation, immediately followed by transient up-regulation of H3 phosphoacetylation and histone H4 acetylation. For each of the studied stresses the observed nucleosomal response was strictly correlated with the induction of stress-type specific genes. The dynamics of histone modifications in BY-2 cells in response to exogenous ABA exhibited a more complex pattern than that evoked by the two abiotic stresses, probably due to superposition of the primary and secondary effects of ABA. A rapid increase in H3 Ser-10 phosphorylation was also observed in whole leaves subjected to high salinity; however, the rate of change in this modification was much slower than in cultured cells. Together, these results indicate that the quiescent BY-2 and T87 cell lines show a typical nucleosomal response to abiotic stresses and ABA treatment and may represent suitable models for the study of chromatin-mediated mechanisms of stress tolerance in plants.

Laparoscopic splenectomy in children: experience in a single institution.

PURPOSE: To assess the safety and effectiveness of laparoscopic splenectomy in children. MATERIALS AND METHODS: Hospital records of 63 patients who underwent laparoscopic splenectomy between 1998 and 2005 were reviewed retrospectively. In 16 patients concomitant cholecystectomy was performed. All procedures were performed by the same surgeon. The indications for splenectomy were hereditary spherocytosis (n = 35), idiopathic thrombocytopenic purpura (n = 22), autoimmune hemolytic anemia (n = 3), and other diseases (n = 3). Details of operative technique were reviewed and their implications on intraoperative complications are analyzed. The postoperative course and long-term results were assessed. RESULTS: There were 35 girls and 28 boys, whose average age was 11.3 years (range, 3.9-19.5 years). There were 7 conversions, mainly at the beginning of the series. A mild degree of intraoperative bleeding was observed in 23 (36.5%) cases. In two cases (3%) severe bleeding led to conversion. Postoperatively, 1 patient required blood transfusion and 1 patient had signs of mild general infection that was treated conservatively. There was no mortality in this series. The mean operation time was 134 minutes for splenectomy and 174 minutes for splenectomy and cholecystectomy. Operative time did not significantly diminish at the end of the 7-year study period. CONCLUSION: Laparoscopic splenectomy in children performed by an experienced team proved to be safe and effective with minimal side effects and should be recommended as a procedure of choice in children who require splenectomy.

Experiences with recombinant activated factor VII in the treatment of severe refractory thrombocytopenia.

Approximately 5% of chronic immune thrombocytopenic purpura (ITP) manifests itself as symptomatic, severe thrombocytopenia requiring splenectomy. The surgical procedure increases the risk of serious hemorrhage, especially in patients refractory to platelet transfusions. Recombinant factor VIIa (rFVIIa) has been found to enhance thrombin generation on activated platelets and may be a promising agent in preventing life-threatening bleedings. The administration of rFVIIa in two patients with severe refractory ITP, who underwent splenectomy, is presented. Combined therapy with agents of different mechanisms of action could be useful in cases with the highest probability of bleeding.

[Surgical treatment for malignancies in children--is prolonged bone marrow suppression an absolute contraindication for surgical procedures?]. / Leczenie chirurgiczne dzieci z choroba nowotworowa--czy przedluzajaca sie aplazja jest bezwzglednym przeciwwskazaniem do interwencji chirurgicznej?

AIM: To analyze the perioperative period in children who required surgery anticipated in the protocol and suffered from prolonged bone marrow suppression. MATERIAL AND METHODS: The surgical treatment of 15 children with prolonged bone marrow suppression, resistant to GM-CSF for 5-15 weeks (M=10), was retrospectively analyzed. Criteria to submit a patient to the group were: neutropenia <1000/ml or/and thrombocytopenia <70,000/ml. Four had thrombocytopenia, 8 neutropenia and 3 cytopenia of both cell lines. Neutropenic patients were divided into two groups: severe neutropenia--<500/ml (2), and moderate--500-1000/ml (7). Children with thrombocytopenia were divided into two groups: with thrombocytes <30,000/ml (2) and between 30,000-70,000/ml (5). RESULTS: Complications (pneumonia and sepsis) were noted in 2 out of 4 children with severe neutropenia, remaining patients had uncomplicated perioperative period. Patients with moderate neutropenia did not show any alarming signs after surgery. As a major haemorrhage we assumed loosing > 30 percent of circulating blood. This was observed only in 1 patient (with thrombocytes <30,000/ml). 13 patients were discharged from our Department between 3-10 days after surgery in good general condition. Two had to be treated for a longer time because of advanced cancers (18 and 21 days). CONCLUSIONS: Neutropenia does not seem to be an absolute contraindication for surgical procedures needed in complex cure of malignancies. In our opinion thrombocyte level > 30,000/ml appears to be safe enough to conduct surgery.