Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study.

The outcome of relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) in adults is poor, with less than 20% of patients surviving at 5 years. Nelarabine is the only drug specifically approved for R/R T-ALL/T-LBL, but the information to support its use is based on limited available data. The aim of this observational phase four study was to provide recent additional data on the efficacy and safety of nelarabine in adults with R/R T-ALL/T-LBL and to evaluate the feasibility and outcome of allogeneic hematopoietic stem cell transplant (SCT) after salvage with nelarabine therapy. The primary endpoints were overall response rate (ORR) and overall survival (OS). Additional endpoints were safety, SCT rate and post-SCT OS. Between May 2007 and November 2018, 118 patients received nelarabine salvage therapy at 27 Italian hematology sites. The median age was 37 years (range 18-74 years), 73% were male, 77 had a diagnosis of T-ALL and 41 of T-LBL, and 65/118 (55%) had received more than two lines of therapy. The median number of nelarabine cycles was two (range 1-4); 43/118 (36%) patients had complete remission (CR), 16 had partial remission (14%) and 59 (50%) were refractory, with an ORR of 50%. The probability of OS, from the first dose of nelarabine, was 37% at 1 year with a median survival of 8 months. The OS at 1 year was significantly better for the 47 patients (40%) who underwent SCT after nelarabine salvage therapy (58% vs 22%, log-rank P < .001). The probability of OS at 2 and 5 years from SCT was 46% and 38%, respectively. Seventy-five patients (64%) experienced one or more drug-related adverse events (AE). Grade III-IV neurologic toxicities were observed in 9/118 (8%) of cases and thrombocytopenia or/and neutropenia (grade III-IV) were reported in 41% and 43% of cases, respectively. In conclusion, this is one of the largest cohorts of adult patients with R/R T-ALL/T-LBL treated in real life with nelarabine. Taking into account the poor prognosis of this patient population, nelarabine represents an effective option with an ORR of 50% and a CR rate of 36%. In addition, 40% of cases following nelarabine salvage therapy could undergo SCT with an expected OS at 2 and 5 years of 46% and 38%, respectively. The safety profile of nelarabine was acceptable with only 8% of cases showing grade III-IV neurological AE.

Evans Syndrome Presenting as an Atypical Complication of SARS-CoV-2 Vaccination.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drastically affected our daily lives, causing millions of deaths worldwide. The early and late complications of this infection are being increasingly revealed on a regular basis; however, an important brake on the spread and especially the lethality of the disease has been guaranteed by the introduction of mRNA-based and viral vector-based COVID-19 Vaccines. Also, an increasing number of adverse effects of the vaccination have been reported to specific pharmacovigilance boards, most of them totally non-serious events that are resolved within one to three days after the administration of the vaccine. In this report, we present a case of Evans syndrome (ES) secondary to SARS-CoV-2 vaccination in an 85-year-old male patient. To the best of our knowledge, this is the first case of ES caused by the COVID-19 vaccination to be reported in the literature.

Water quality and solute sources in the Marsyangdi River system of Higher Himalayan range (West-Central Nepal).

Surface waters, cold and hot springs were collected in different catchments along the Marsyangdi basin, in the Himalayan Range of West-Central Nepal, during the post-monsoon season in 2017 and analyzed for major ions and trace elements, with the aim of assessing the sources of dissolved species and to contribute in watershed planning. The major element data indicate that surface waters coming from the Tethyan Himalayan Sequence (THS) range from the Ca-Mg-HCO3 to the Ca-Mg-HCO3-SO4 water-types and reflect a two-component mixing of waters from carbonate- and sulfate-bearing sources. The latter component is attributable to sulfide oxidation with minor silicate weathering. In the Greater Himalaya Sequence (GHS), alteration of pedogenetic carbonates formed in response to silicate weathering under a variable CO2 gas pressure dominates, yielding a Ca-HCO3 signature. The stability diagram in the K2O-Al2O3-SiO2-H2O system and the paired increases in Ca2+, Na+, K+ and silica indicate that degradation of silicate minerals through kaolinization and possibly plagioclase albitization reactions is the main process for hot groundwater. Cold and hot springs define a trend of increasing Li, SiO2 and Cl-, suggesting that lithium was leached from silica-rich sources, such as pegmatite dykes and sills occurring in host rocks, and concentrated into halite-bearing salt aquifers. In hot waters Sb, As and Tl exceed the EU and USEPA thresholds. Tl is usually incorporated into pyrite and correlates with Li indicating the occurrence of an ore-bearing zone possibly related to hydrothermal activity at the transition zone between THS and GHS, as suggested by the relatively high Ba, Ni, Cu, Sb, As and Mn contents. The obtained data on water quality have significant implications for people living along the Upper Marsyangdi River in the management of water resources, especially in terms of the enhancement of cold water aquaculture and hot water uses for recreation purposes and tourism.