​Donna Kirby: EHA/HemaSphere, The Hague, The Netherlands

Are you aware that each month our Editor in Chief picks a few of our articles to call out as ‘Editors Highlights’ ? These are articles called out for extra notice: either for new data, exciting breakthroughs, novel use of technology, or general interest  We feature them in our HemaSphere monthly newsletter, as well as on LinkedIn and Twitter.

For your convenience, we have compiled a quarterly round up of the linked articles to catch you up on what you might have missed. 

January:

Pathogen-specific T-cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond 

Yannaki E et al

Adoptive immunotherapy with pathogen-specific T cells (pSTs) can restore immunity and prevent or treat opportunistic infections/diseases post transplantation or even outside of this context. This could provide a platform to also target novel emerging pathogens, including SARS-COV-2. The journey of evolution of immunotherapy with pSTs against infections and virus-associated malignancies from the early steps of development up to clinical translation is presented in this review. Will adoptive immunotherapy with pSTs become a standard treatment in the future?

Outcome Prediction in Patients With Large B-cell Lymphoma Undergoing Chimeric Antigen Receptor T-cell Therapy   

Voltin et al

​While the introduction of chimeric antigen receptor (CAR) T-cell therapy has led to a fundamental shift in the management of relapsed and refractory large B-cell lymphoma, our understanding of risk factors associated with non-response is still insufficient. Relevant patient and disease characteristics should be considered when managing patients with large B-cell lymphoma who are due to undergo CAR T-cell therapy, and this study shows that in this context, higher metabolic tumor volume and SUVmax as well as extra-nodal disease are associated with significantly inferior patient outcome.

February:

Hematopoietic Cell Autonomous Disruption of Hematopoiesis in a Germline Loss-of-function Mouse Model of RUNX1-FPD  

Ernst et al

RUNX1 familial platelet disorder (RUNX1-FPD) is caused by germline loss-of-function mutations in the RUNX1 gene, and is characterized by thrombocytopathy, thrombocytopenia, and an increased risk of developing hematologic malignancies mostly of myeloid origin. However, what are the potential contributions of ancillary, non-hematopoietic cells to the hematopoietic manifestations of this disease? Using a mouse model of RUNX1-FPD that mimicked impaired residual RUNX1 function, authors uncovered hematopoietic cell-intrinsic platelet deficiency, increased myeloid potential, and decreased lymphoid potential.​

Impact of Ultra High-risk Genetics on Real-world Outcomes of Transplant-eligible Multiple Myeloma Patients                

Panopoulou et al

Ultra high-risk genetics predict early relapse and poor subsequent outcomes post standard care in autologous stem cell transplantation. This was further evaluated via a retrospective review of records of patients with newly diagnosed multiple myeloma (NDMM). Double hit genetics — ≥2 adverse markers: t(4;14), t(14;16), t(14;20), gain(1q), and del(17p) — were associated with a shortened progression-free survival (HR = 4.27, P < 0.001) and overall survival (HR = 4.01, P = 0.03), and characterized most early relapses. Results support the real-world utility of extended genetic profiling for improved risk prediction in patients with NDMM.

March:

Simultaneous Inhibition of PI3Kgamma and PI3Kdelta Deteriorates T-cell Function with Implications for Chronic Lymphocytic Leukemia  

Roessner et al​

The goal of this study is a comprehensive analysis of four PI3K inhibitors, idelalisib, umbralisib, duvelisib, and eganelisib, and their impact on CD4 and CD8 T-cell activation and function. By performing treatment studies with naïve and chronic lymphocytic leukemia-experienced T-cells of human or murine origin, authors show that inhibition of PI3K-delta and PI3K-gamma limits the activation and proliferation of T cells. Unexpectedly, the authors observed an additive effect of dual inhibition of PI3K-delta and PI3K-gamma on T-cell function.

Prediction of Nonrelapse Mortality in Patients With Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia Receiving Allogeneic Stem Cell Transplantaion With Posttransplantation Cyclophosphamide-based Graft Versus Host Disease Prophylaxis         

Versluis et al

In this study, authors develop and validate a novel, post-transplant cyclophosphamide (PTCY)-specific risk score model for nonrelapse mortality (NRM) prediction in patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) who receive PTCY-based graft vs host disease prophylaxis. This novel NRM risk score model better predicts NRM and overall survival at 2 years compared to existing models, which might be due to the specific toxicities of high-dose cyclophosphamide.​

You can always find the latest issue here​, and as always, our content is fully open access. ​