Hematolological manifestations of COVID-19: From cytopenia to coagulopathy

This is an accepted manuscript of an article published by Wiley in European Journal of Haematology on 14/07/2020, available online: https://doi.org/10.1111/ejh.13491 The accepted version of the publication may differ from the final published version.Emerging data from the management of patients with Coronavirus Disease 2019 (COVID‐19) suggests multisystemic involvement, including the hemopoietic system. The hematological manifestations of COVID‐19 include blood count anomalies notably lymphopenia and neutrophilia which are of prognostic significance. Hyperferritinemia and elevated lactate dehydrogenase have also been associated with increased mortality. Furthermore, there is considerable evidence of a distinct coagulopathy associated with COVID‐19 characterised by elevated D‐dimers and an increased risk of thrombotic events. This comprehensive review summarises the latest evidence from published studies and discusses the implications of the various hematological manifestations of COVID‐19 with a view to guiding clinical management and risk stratification in this rapidly evolving pandemic.CA is a recipient of a clinical research fellowship funded by the CRUK-City of London Centre Clinical Academic Training Programme Award [C355/A28852

A Simple and Robust Single-Step Method for CAR-Vδ1 γδT Cell Expansion and Transduction for Cancer Immunotherapy

The γδT cell subset of peripheral lymphocytes exhibits potent cancer antigen recognition independent of classical peptide MHC complexes, making it an attractive candidate for allogeneic cancer adoptive immunotherapy. The Vδ1-T cell receptor (TCR)-expressing subset of peripheral γδT cells has remained enigmatic compared to its more prevalent Vγ9Vδ2-TCR and αβ-TCR-expressing counterparts. It took until 2021 before a first patient was dosed with an allogeneic adoptive Vδ1 cell product despite pre-clinical promise for oncology indications stretching back to the 1980s. A contributing factor to the paucity of clinical progress with Vδ1 cells is the lack of robust, consistent and GMP-compatible expansion protocols. Herein we describe a reproducible one-step, clinically translatable protocol for Vδ1-γδT cell expansion from peripheral blood mononuclear cells (PBMCs), that is further compatible with high-efficiency gene engineering for immunotherapy purposes. Briefly, αβTCR- and CD56-depleted PBMC stimulation with known-in-the-art T cell stimulators, anti-CD3 mAb (clone: OKT-3) and IL-15, leads to robust Vδ1 cell expansion of high purity and innate-like anti-tumor efficacy. These Vδ1 cells can be virally transduced to express chimeric antigen receptors (CARs) using standard techniques, and the CAR-Vδ1 exhibit antigen-specific persistence, cytotoxicity and produce IFN-γ. Practicable, GMP-compatible engineered Vδ1 cell expansion methods will be crucial to the wide-spread clinical testing of these cells for oncology indications

Clinical characteristics and outcomes of IgD myeloma: experience across UK national trials

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.Immunoglobulin D (IgD) myeloma is a subtype often considered to have adverse features and inferior survival, but there is a paucity of data from large clinical studies. We compare the clinical characteristics and outcomes of patients with IgD myeloma from UK phase 3 myeloma trials analyzed in 2 groups: old (1980-2002) and recent (2002-2016) clinical trials, based on the time of adoption of novel myeloma therapies. Patients with IgD myeloma comprised 44 of 2789 (1.6%) and 70 of 5773 (1.2%) of the old and recent trials, respectively. Overall, IgD myeloma was associated with male predominance, low-level paraproteinemia (,10g/L), and l light chain preference. The frequency of ultra-high-risk cytogenetics was similar in IgD myeloma compared with other subtypes (4.3% vs 5.3%, P . .99). Despite the old trial series being a younger group (median age: 59 vs 63 years, P 5 .015), there was a higher frequency of bone lesions, advanced stage at diagnosis, worse performance status, and severe renal impairment compared with the recent trials. Furthermore, the early mortality rate was significantly higher for the old trial series (20% vs 4%, P 5 .01). The overall response rate following induction therapy was significantly higher in the recent trials (89% vs 43%, P, .0001), and this was consistent with improved median overall survival (48 months; 95% confidence interval [CI] 35-67 months vs 22 months; 95% CI, 16-29 months). Survival outcomes for IgD myeloma have significantly improved and are now comparable to other myeloma types because of earlier diagnosis, novel therapies, and improved supportive care.Published versio

Clinical characteristics and outcomes of IgD myeloma : experience across UK national trials

Immunoglobulin D (IgD) myeloma is a subtype often considered to have adverse features and inferior survival, but there is a paucity of data from large clinical studies. We compare the clinical characteristics and outcomes of patients with IgD myeloma from UK phase 3 myeloma trials analyzed in 2 groups: old (1980-2002) and recent (2002-2016) clinical trials, based on the time of adoption of novel myeloma therapies. Patients with IgD myeloma comprised 44 of 2789 (1.6%) and 70 of 5773 (1.2%) of the old and recent trials, respectively. Overall, IgD myeloma was associated with male predominance, low-level paraproteinemia ( .99). Despite the old trial series being a younger group (median age: 59 vs 63 years, P = .015), there was a higher frequency of bone lesions, advanced stage at diagnosis, worse performance status, and severe renal impairment compared with the recent trials. Furthermore, the early mortality rate was significantly higher for the old trial series (20% vs 4%, P = .01). The overall response rate following induction therapy was significantly higher in the recent trials (89% vs 43%, P < .0001), and this was consistent with improved median overall survival (48 months; 95% confidence interval [CI] 35-67 months vs 22 months; 95% CI, 16-29 months). Survival outcomes for IgD myeloma have significantly improved and are now comparable to other myeloma types because of earlier diagnosis, novel therapies, and improved supportive care. This trial was registered at clinicaltrials.gov as # NCT01554852