This Week in Hematology — Jun 4, 2026

Welcome to This Week in Hematology. This week we're covering 8 notable papers spanning new therapeutic strategies in lymphoma and leukemia, fundamental new insights into hemostasis, and a key trial in pediatric hyperinflammation. Let's dive in.

First, we look at long-term outcomes and novel targets in lymphoid malignancies. A report in *Blood* presents the five-year survival outcomes from the TRANSCEND NHL 001 study of lisocabtagene maraleucel, or liso-cel, in patients with relapsed or refractory large B-cell lymphoma [6]. This provides a crucial long-term look at the durability of this CAR-T therapy.

The Study Investigators followed 345 leukapheresed patients, of whom 270 received liso-cel. The primary focus was on the 257 patients in the efficacy-evaluable set.

Results Among efficacy-evaluable patients, the median overall survival was 27.5 months. The estimated five-year overall survival rate was 38 percent. When looking at disease-specific survival, which excludes deaths from causes other than disease progression, the median was 67.8 months, with an estimated five-year rate of 52 percent. The authors note that most deaths occurred within two years of infusion, and no new long-term safety signals emerged. These data support the curative potential of liso-cel for a subset of patients with relapsed or refractory large B-cell lymphoma.

While CAR-T therapy is an established modality, the search for new targets in other diseases continues. A study, also in *Blood*, focuses on a high-risk group in multiple myeloma [7].

Background Deletion of 17p is one of the most adverse cytogenetic abnormalities in multiple myeloma. Researchers sought to identify a targetable vulnerability in these specific myeloma cells.

The Study By integrating RNA sequencing data from patient cells with genetic data from myeloma cell lines, they identified the kinase PKMYT1 as a potential therapeutic target. They then tested this hypothesis using both genetic suppression and a selective pharmacological inhibitor, RP-6306.

Results Inhibiting PKMYT1 triggered DNA damage and mitotic catastrophe, leading to cell death preferentially in the del(17p) myeloma cells, while largely sparing cells without this deletion and healthy cells. In both xenograft and syngeneic mouse models, the inhibitor RP-6306 reduced tumor burden and extended survival. This study nominates PKMYT1 inhibition as a promising biomarker-driven therapeutic strategy for patients with high-risk, del(17p) multiple myeloma.

Turning to acute myeloid leukemia, two papers this week address the linked challenges of therapeutic resistance and disease monitoring. In the *British Journal of Haematology*, investigators explored why some AML patients are resistant to venetoclax [3]. They focused on patients with high expression of the gene EVI1, a subgroup known to have a poor prognosis.

Findings The study confirmed that patients with EVI1-high AML had inferior outcomes with both chemotherapy and venetoclax-based regimens. The researchers then uncovered the mechanism in vitro: elevated EVI1 expression leads to activation of the PI3K/AKT signaling pathway. This, in turn, stabilizes the MCL-1 protein, which prevents cancer cell death and thus confers resistance to venetoclax.

Implications Importantly, the team showed that co-treatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity to venetoclax in both cell lines and primary AML samples with high EVI1 expression. This suggests a potential combination strategy to overcome resistance in this high-risk AML subset.

As we refine therapies for AML, refining how we monitor response is equally critical. A companion technical note from the European LeukemiaNet, published in *Blood*, provides recommendations on this front [5]. The document addresses the use of next-generation sequencing for FLT3-ITD measurable residual disease, or MRD, testing for patients in remission from AML. This type of MRD testing is now recommended by updated clinical standard of care guidelines, and this paper provides the important laboratory and clinical recommendations for how to perform and interpret such testing.

Next, we have a trio of papers that take us back to the fundamentals of hemostasis, from platelet production to function. First, a study in *Blood* explores a key metabolic step in making platelets, a process called thrombocytopoiesis [4]. The work focuses on an enzyme called glutamine synthetase, or GLUL.

Findings The researchers found that GLUL is highly expressed in platelet-producing megakaryocytes and that its levels increase as the cells mature and become polyploid. They discovered that GLUL's crucial role is to detoxify ammonia, which accumulates during the massive DNA synthesis required for megakaryocyte maturation. In megakaryocytes lacking GLUL, ammonia builds up, leading to lysosomal and mitochondrial damage and cell death, which impairs platelet production. The investigators also identified a potential GLUL agonist, called Fulvotomentoside A, which was able to promote thrombocytopoiesis in mouse models after radiation and chemotherapy. This work uncovers a new biological pathway in megakaryocyte maturation and a potential avenue for regulating platelet production.

From production, we move to function. Another paper in *Blood* identifies a new role for a plasma protein in regulating platelet activity [8]. The protein is Histidine-rich Glycoprotein, or HRG.

The Study Researchers investigated how HRG, which is known to localize on the platelet surface, might directly regulate adhesion and aggregation. They showed that HRG binds to two key platelet receptors: GPIb-alpha on resting and activated platelets, and GPIIb/IIIa on activated platelets.

Results By binding to these receptors, HRG competes with von Willebrand factor and fibrinogen, respectively. The functional consequence is that HRG attenuates platelet agglutination, aggregation, and thrombus growth under high-shear conditions. The study also notes that plasma HRG levels in patients with sepsis or COVID-19 were about half those of healthy controls. When they mimicked these low levels in vitro, it promoted a hyperreactive platelet phenotype. This suggests that HRG is a natural modulator of platelet function, and its depletion in inflammatory states may contribute to thrombosis.

These fundamental discoveries are the building blocks for future treatments. A review in *Blood Advances* this week surveys the landscape of novel therapies for von Willebrand Disease [2]. The authors highlight that after decades of reliance on classic approaches, a new wave of innovation is underway. This includes repositioning molecules from other bleeding disorders, as well as developing new antibodies, engineered factors, siRNAs, and even genome editing tools, some of which are now entering clinical evaluation. This reflects a broader trend of leveraging basic science insights, like those in the GLUL and HRG papers, to create next-generation therapeutics.

Finally, we turn to a rare but life-threatening condition in children: hemophagocytic lymphohistiocytosis, or HLH. A prospective trial in *Blood Advances*, called HLHRUXO, evaluated a ruxolitinib-containing regimen for pediatric HLH [1]. HLH is a severe hyperinflammatory syndrome driven by cytokines that signal through the JAK-STAT pathway, making the JAK1/2 inhibitor ruxolitinib a logical therapeutic candidate.

The Study This was a multi-institutional trial in eight children with either newly diagnosed or relapsed/refractory HLH. Patients received ruxolitinib combined with dexamethasone, with or without etoposide, for eight weeks.

Results The regimen was found to be safe, with no dose-limiting adverse events. All patients had a favorable response at one week. The best results were seen in patients with newly diagnosed disease. All five newly diagnosed patients—three with primary HLH and two with secondary HLH—achieved a complete response at eight weeks and were alive at one year. Outcomes were less favorable in the two patients with relapsed/refractory primary HLH, who ultimately died. The findings confirm the safety of this ruxolitinib-containing regimen and suggest it is a highly effective component of frontline therapy for children with newly diagnosed HLH.

Editor's Pick If you only have time for one paper this week, make it the five-year survival data for lisocabtagene maraleucel in large B-cell lymphoma, published in *Blood* [6]. These results from the TRANSCEND NHL 001 study provide crucial long-term evidence supporting the curative potential of this CAR-T therapy for a significant fraction of patients.

Clinical Bottom Line Here are the key takeaways from this week in Hematology. First, five-year follow-up of the TRANSCEND study shows that liso-cel offers durable, potentially curative responses for patients with relapsed/refractory large B-cell lymphoma, with a five-year overall survival rate of 38 percent in the efficacy-evaluable population. Second, for the subset of AML patients with high EVI1 expression who are resistant to venetoclax, preclinical data suggests adding an AKT inhibitor like capivasertib could be an effective strategy to restore sensitivity. Third, a reminder that NGS-based MRD testing for FLT3-ITD in patients with AML in remission is now a recommended standard, and new technical guidelines are available to support its implementation. Fourth, in pediatric HLH, a prospective trial shows a ruxolitinib-containing regimen is safe and highly effective as frontline therapy, with all newly diagnosed patients in the small study achieving a complete response. Finally, new basic science is identifying novel regulators of platelet production and function, such as GLUL and HRG, which may become future therapeutic targets for managing thrombocytopenia or thrombosis.

That's your roundup for This Week in Hematology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.