Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma.

BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. RESULTS: Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

Distal fusion level, complications, and reoperations in individuals with cerebral palsy undergoing surgery for scoliosis.

PURPOSE: To compare radiological outcome, complications and reoperations in individuals with cerebral palsy and scoliosis fused to the fifth lumbar vertebra (L5), the sacrum, or the ilia. METHODS: 208 individuals were identified in the national quality registry Swespine. Lowest level of fusion was L5 in 58, the sacrum in 92, and the ilia in 58 individuals. A subanalysis on 58 matched pairs operated to L5 or the pelvis (sacrum = 42, ilia = 16) with similar pelvic obliquity (± 5°) was performed. RESULTS: The median (interquartile range) follow-up for the last radiograph was 1.7 (1.7) years and for reoperations 6.0 (5.9) years. Preoperatively, median Cobb angle of the major curve was 65° (23°) in the L5 group, 68° (28°) in the sacrum group, and 78° (25°) in the ilia group (p = 0.006). Preoperative median pelvic obliquity according to Maloney was 16° (19°), 21° (13°), and 27° (28°), respectively (p = 0.004). Immediate postoperative Cobb angles were 28° (18°), 28° (16°), and 32° (25°), respectively (p = 0.11). Immediate postoperative pelvic obliquity was 7° (10°), 7° (8°), and 8° (10°), respectively (p = 0.28). The median change in pelvic obliquity from the first to the last postoperative radiograph was - 5° (7°), - 3° (6°), - 3° (6°), respectively (p = 0.55). 7 (12%), 11 (12%), and 7 (12%) patients required at least one reoperation (p = 1.0), respectively. In the matched analysis, no significant differences in the radiological outcomes were found (all p ≥ 0.38). CONCLUSIONS: Maintained curve and pelvic obliquity correction with no significant difference in complication and reoperation rates were found irrespective of distal fusion level.

Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group.

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.

Clinicobiological features and prognostic impact of diffuse large B-cell lymphoma component in the outcome of patients with previously untreated follicular lymphoma.

BACKGROUND: The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. PATIENTS AND METHODS: All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. RESULTS: The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. CONCLUSIONS: The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.

Automation of blood component preparation from whole blood collections.

BACKGROUND AND OBJECTIVES: Automation of blood component preparation (BCP) from whole blood (WB) collections is increasingly being widespread implemented. This review summarizes the quality of blood components obtained with new automated devices. MATERIALS AND METHODS: We reviewed available literature on the quality of blood components obtained with new automated devices developed in the 2000s. RESULTS: Blood components obtained with the new devices met European standards. Of note, compared with platelet concentrates obtained with manual methods, automation of BCP improved the consistency of the final products. CONCLUSION: The complete automation of BCP from WB collections is still in development and it represents a huge change in paradigm.

Effects of dimethyl sulfone (DMSO2) on early gametogenesis in Caenorhabditis elegans: ultrastructural aberrations and loss of synaptonemal complexes from pachytene nuclei.

The free-living nematode Caenorhabditis elegans has been used extensively for studies in developmental and reproductive genetics. Recently, toxicologic studies have been initiated using specific sex chromosome mutations. In the present study, high incidence of male (him) mutants, him-5 and him-8, were treated with dimethyl sulfone (DMSO2), the primary metabolite of dimethyl sulfoxide (DMSO). In addition to differential effects on X-chromosome nondisjunction, loss of viability and fertility were observed. Much lower concentrations of DMSO2 were required to elicit the same aberrational effects characteristic of DMSO (1); thus, the toxicity of the former was significantly more potent. The observed decrease in life span was associated with senescent morphology of meiotic prophase nuclei, such that nuclei from young and old specimens could not be differentiated. Aging in oocytes at pachytene is characterized by nucleo-cytoplasmic aberrations, increased density of the nucleoplasm and cytoplasm, and decrease in numbers of mitochondria. Increasing concentrations of DMSO2 resulted in a corresponding decrease in fertility and increased production of abnormal gametes. At DMSO2 concentrations higher than 1.0%, synaptonemal complexes (SC) were absent from pachytene nuclei; thus, effective pairing and segregation of homologous chromosomes was prohibited. Since the SC is essential for regulating pairing and subsequent separation of bivalents, the lack of an SC explains the loss of fertility, due to the production of unbalanced gametes, observed in DMSO2-treated specimens.

[The quality of a restaurant service at a geriatric rehabilitation facility]. / Valutazione oggettiva e soggettiva della qualità di un Servizio di Ristorazione collettiva in una Struttura di Riabilitazione Geriatrica.

The aim of our study was to measure the quality of a restaurant service of a geriatric rehabilitation and long-term setting as it is perceived from patients compared with an objective measure of the quality. We have also verified the weight of the restaurant service on the whole quality of the hospital. Our data showed some problems in the organisation of the service, a substantially negative judgment from patients, the necessity to integrate subjective judgments with objective evaluations. The data confirmed also the importance that patients give to taste and variability of food and to the way in which it is presented. The results we obtained suggested an audit of the organisation of the restaurant service. The outcome of the proposed changes will be followed up and bring, eventually, to further arrangements.

Effects of dimethyl sulphoxide on early gametogenesis in Caenorhabditis elegans: ultrastructural aberrations and loss of synaptonemal complexes from pachytene nuclei.

In Caenorhabditis elegans, loss of viability and fertility was observed after treatment with dimethyl sulphoxide (DMSO). The decrease in life span is associated with senescent morphology of meiotic prophase nuclei, such that nuclei from young and old specimens cannot be differentiated. Aging in oocytes at the pachytene stage of meiotic prophase is characterized by nucleo-cytoplasmic aberrations, increased density of the nucleoplasm and cytoplasm and decrease in numbers of mitochondria (Goldstein and Curis, 1987). Increasing concentrations of DMSO result in decrease in fertility and increased production of abnormal gametes. At DMSO concentrations higher than 5.0%, synaptonemal comlexes (SC) are absent from the nuclei, thus, effective pairing and segregation of homologous chromosomes is not possible. The absence of SCs may be the result of: (1) a premeiotic colchicine-like effect which influences pairing of chromosomes; (2) changes in the structure of the DNA due to DMSO binding that results in changes in expression of the DNA; and (3) changes in temporal DNA synthesis in response to DMSO. Since the SC is essential for regulating pairing and subsequent separation of bivalents, the lack of an SC explains the loss of fertility, due to the production of unbalanced gametes, observed in DMSO treated specimens.

Hypervitaminosis E and gametogenesis in Caenorhabditis elegans.

Expected benefits, i.e. increasing life span and vitality, from ingesting d,1-alpha tocopherol (vitamin E), are not realized using vitamin E acetate (VEA) since the acetate form is only slowly converted to vitamin E in either mammalian or nematode tissues. The resultant accumulation of VEA in the cytosol is toxic, which results in aberrations in nuclear morphology, decreased life span and production of progeny, increased mean reproductive day and general loss of vitality. Incorporation of VEA into membranes results in allosteric changes in membrane structure. Such changes are proportional to increasing concentrations of VEA, thereby inhibiting the attachment of the telomere to the nuclear envelope. Reproductive and chromosomal strategies are compromised such that synaptonemal complexes, normally found during pachytene in oocytes, are rarely present in those nematodes exposed to high concentrations of VEA. The resultant loss of SCs correlates with decreased progeny and the chromosomal aberrations characteristic of hypervitaminosis E.