Blood Cancer Discovery最新文献

Significance: A new model of intratumor and interpatient heterogeneity in response to drug combinations explains and predicts the results of clinical trials of curative-intent treatments for DLBCL. This model can be used to understand and inform optimal design of curative drug combinations and clinical trials. See related commentary by Goldstein et al., p. 153.

Significance: Our investigation of the SOCS1 pathway in AML and T-cell interactions provides insights into potential mechanisms of resistance of AML to allogeneic hematopoietic stem cell transplantation and demonstrates the potential of targeting SOCS1 and its downstream mediators to enhance antileukemic T-cell activity. See related commentary by Fry, p. 157.

Artificial intelligence could enhance chimeric antigen receptor T-cell therapy outcomes through optimization of all steps, from target identification, vector design, and manufacturing to personalized data-driven clinical decisions. In this report, we highlight steps toward unlocking this potential, including the need for standardized, comprehensive data repositories as a way for addressing barriers to artificial intelligence learning, such as data heterogeneity and patient privacy.

Since the recognition of the allogeneic graft-versus-leukemia effect, acute myeloid leukemia (AML) has been identified as a T cell-targetable malignancy, but success with modern forms of immunotherapy has been slower than anticipated. In this issue, we discuss the biological barriers to the treatment of AML with T-cell therapy revealed by recent reports, including mechanistic insights into AML resistance to T cell-mediated killing by Tin and colleagues. See related article by Tin et al., p. 217.

Significance: SPMs that develop in patients with multiple myeloma have a deleterious impact on survival. Patients with CH may be at risk of developing SPMs, which could potentially be avoided through individualized treatment. However, our results suggest that screening for CH at diagnosis has limited utility.

Significance: This review underscores our shared responsibility to champion multidimensional strategies rooted in basic and translational science, community involvement, and societal responsiveness for a meaningful impact. Unifying themes include the need to enhance collaborative infrastructure to engage laboratory researchers, epidemiologists, data scientists, clinicians, patients, community leaders, and policymakers; patient-level support services; outreach, education, and navigation for patients at the community level; recruitment and retention of underrepresented groups in the healthcare and research workforce; and funding for these efforts.

Significance: In recent years, remarkable technological advances have illuminated aspects of the pathogenesis of myeloid malignancies-yet outcomes for patients with these devastating diseases have not significantly improved. We posit that a synthesized view of the three dimensions through which hematopoietic cells transit during their healthy and diseased life-clonal evolution, stem cell hierarchy, and ontogeny-promises high yields in new insights into disease pathogenesis and new therapeutic avenues.

Abstract: Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immunosuppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. In this study, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, and tisagenlecleucel 24.7%). Following infusion, patients remain persistently immunosuppressed, with 48.1% having CD4+ T-cell counts <200/µL and the median CD3-CD19+ B-cell counts remaining zero through 1 year after CAR-T therapy. IR differences exist by product, with the fastest CD4+ T-cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7−CD45RA− effector memory subset. NK cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR, 0.65; 95% confidence interval, 0.48–0.88) and overall survival (HR, 0.64; 95% confidence interval, 0.44–0.92) and inversely correlated with inflammatory markers measured at the time of infusion.

Significance: This study reveals differences in IR patterns after CAR-T therapy in patients with large B-cell lymphoma, with early NK cell recovery emerging as a key predictor of survival. These findings provide potential future avenues of research for improving patient outcomes and tailoring post-therapy management strategies to mitigate relapse risk.

Significance: As survival of HCT recipients continues to improve, late treatment effects gain importance. We demonstrate that pediatric HCT recipients show increased risk of CH compared with age-matched controls. Prospective studies are crucial to understand the clinical implications of posttransplant CH in this young population.

Significance: In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.