This Week in Hematology — May 21, 2026

Welcome to This Week in Hematology. This week we're covering 10 notable papers spanning new therapeutic targets and prognostic markers in leukemia and myeloma, evolving management strategies in thrombosis, and a major population study reassessing long-term risks in sickle cell trait. Let's dive in.

Advances in Malignant Hematology

We begin this week in malignant hematology, with several key papers from the journal *Blood* exploring new therapeutic avenues and refining prognostic markers in AML, ALL, and multiple myeloma.

The Study Two papers offer important insights for acute myeloid leukemia. First, a study by Duployez and colleagues challenges our current approach to risk stratification based on FLT3-ITD mutations [5]. Current guidelines focus on so-called "macroclones" with an allelic ratio of 0.05 or higher. This post-hoc analysis of the large BIG-1 trial used sensitive next-generation sequencing to look for low-level "microclones," with an allelic ratio between 0.0004 and 0.05.

Results They found these microclones in over 17 percent of patients who were previously considered FLT3-ITD negative. Critically, these microclones were independently associated with an increased risk of relapse. The two-year cumulative incidence of relapse was 45 percent in patients with microclones, nearly identical to the 42 percent seen in patients with macroclones, and substantially higher than the 29 percent in patients with no FLT3-ITD detected. The findings were particularly relevant in NPM1-mutated AML, where both micro- and macroclones were linked to higher MRD levels and increased relapse. This suggests that our current testing thresholds may be missing a significant group of high-risk patients.

Discussion Supporting the theme of targeted therapy in high-risk AML, a second paper in *Blood* from Creamer and colleagues provides a compelling mechanism for the use of venetoclax in AML with a complex karyotype [6]. It’s known that these leukemias often have TP53 mutations and chromosome 5q deletions, but how this drives the accumulation of chromosomal abnormalities has been unclear. Using a patient-derived stem cell model, the investigators showed that it was the combination of a TP53 mutation plus the 5q deletion—not the TP53 mutation alone—that drove the evolution of a complex karyotype. These aneuploid cells shared a common gene expression signature marked by upregulation of the anti-apoptotic factor BCL2. This created a targetable vulnerability, as the BCL2 inhibitor venetoclax effectively eradicated these aneuploid clones in their model.

This BCL2 theme continues in a study on acute lymphoblastic leukemia. Also in *Blood*, Gong and colleagues report results from a phase 2 trial in newly diagnosed Philadelphia-negative ALL in adolescents and adults [3]. They combined the BCL2 inhibitor venetoclax with a pediatric-inspired chemotherapy regimen. The results were impressive. The primary endpoint, MRD negativity by flow cytometry after induction, was achieved in 73 percent of responders. After a median follow-up of about 19 months, the estimated 2-year overall and disease-free survival rates were approximately 79 percent and 77 percent, respectively, which was superior to historical controls. The safety profile was manageable, consisting mainly of expected hematologic toxicities and infections.

Finally, in multiple myeloma, we have a report on a very difficult-to-treat population: patients with relapsed or refractory disease that has spread outside the bone, known as extraosseous extramedullary disease. In a phase 2 trial published in *Blood*, Zhou and colleagues tested a novel bispecific CAR T-cell therapy targeting both BCMA and GPRC5D [8]. The therapy induced a remarkable overall response rate of 97 percent, with 43 percent achieving a stringent complete response and MRD negativity. However, these responses were not durable for many. The median progression-free survival was only 5.8 months. While median overall survival was not reached, this highlights the ongoing challenge of achieving lasting remissions in this high-risk group, even with potent new immunotherapies. Cytokine release syndrome occurred in 73 percent of patients, but all cases were grade 1 or 2, and neurotoxicity was rare.

Hemostasis and Thrombosis

Next, we turn to hemostasis and thrombosis, with updates on clinical management and a look at future technologies.

In the *Journal of Thrombosis and Haemostasis*, a large comparative cohort study by Ko and colleagues examined outcomes in patients with splanchnic vein thrombosis, or SVT [1]. This rare form of VTE is often associated with myeloproliferative neoplasms, but it was unclear if these patients required different management. The study pooled data on nearly 1200 SVT patients, about 16 percent of whom had an MPN.

The Study Investigators found that anticoagulant management was similar between groups, with about three-quarters of all patients starting on therapy within 30 days. More importantly, the 6-month clinical outcomes were also similar. The cumulative incidence of recurrent thrombosis was 2.5 percent, and major bleeding was 4.5 percent, with no significant differences between patients with and without an MPN. This suggests that for the purposes of short-term anticoagulation management, MPN-related SVT can be approached similarly to non-cirrhotic, non-malignant SVT.

While that study provides some clinical clarity, a perspective piece in the same journal by Shaw and Ansell highlights a major area of uncertainty: how to interpret DOAC levels [2]. The authors argue that while we increasingly need rapid DOAC testing for urgent situations like major bleeding or emergent surgery, the field lacks consensus on what constitutes a clinically meaningful result. They point out that widely used cutoffs, such as 30 or 50 nanograms per milliliter, are pragmatic but not based on strong pharmacodynamic data linking specific drug levels to bleeding risk or residual anticoagulant effect. They call for future research to establish these critical links to guide bedside decisions.

Looking to the future of hemostasis, a preclinical study in *Science Translational Medicine* introduces a potential new topical hemostatic agent [4]. Researchers developed what they call a high phosphatidylserine-exposed procoagulant platelet, or hPPL. This product is derived from isolated platelets that are reprogrammed via induced apoptosis to robustly expose phosphatidylserine on their surface, a key trigger for coagulation. In murine and porcine models of liver injury and gastric ulcer bleeding, this agent demonstrated superior hemostatic efficacy compared to existing clinical products. Notably, it worked well even in the presence of antiplatelet therapy. The mechanism involves not just the phosphatidylserine, but also an upregulation of prostaglandin E2 signaling, which further amplifies platelet activation. While still in early development, this represents a promising new approach for managing difficult-to-control hemorrhage.

Finally, a commentary in *Blood* by Dr. Marie Scully reminds us of the persistent challenges in managing refractory thrombotic thrombocytopenic purpura, a key area where innovation is still needed [10].

Reassessing Risk in Common Hematologic Conditions

Finally, we look at two common concerns in benign hematology, with a major study on sickle cell trait and a direct call to action on iron deficiency.

The centerpiece is a large study from the United Kingdom Biobank, published in *Blood* by Warny and colleagues, which provides important clarity on the long-term risks associated with sickle cell trait [7]. Uncertainty has persisted for decades about whether being a carrier shortens lifespan or predisposes to cardiovascular disease. This study prospectively followed over 467,000 individuals, including more than 1,200 with genetically confirmed sickle cell trait, for a median of 15 years.

Results The main finding is reassuring: individuals with sickle cell trait were not at increased risk of all-cause death or cardiovascular death. They also had no increased risk for myocardial infarction, ischemic stroke, pulmonary embolism, or heart failure. However, the study did uncover important associations. Carriers had a 30 percent increased risk of developing diabetes, a 46 percent increased risk of chronic kidney disease, and a 24 percent higher odds of hypertension. The study also offers a crucial insight into why past research may have been misleading. When the investigators re-analyzed the data using hospital diagnosis codes to identify SCT carriers, instead of genetic data, they found a markedly increased risk of death and stroke. This strongly suggests that previous hospital-based studies suffered from selection bias, as individuals with SCT who come to medical attention are more likely to have other comorbidities.

Lastly, a brief but important commentary in *Blood* from Dr. Jacquelyn Powers delivers a simple, actionable message in its title: "No need to wait: treat iron deficiency in the hospital" [9]. This serves as a reminder that this common and easily treatable condition is frequently overlooked during inpatient stays, representing a missed opportunity to improve patient outcomes.

Editor's Pick

If you only have time for one paper this week, make it the study by Duployez and colleagues in *Blood* on FLT3-ITD microclones in AML [5]. This work challenges our current diagnostic thresholds and suggests that a significant number of patients currently classified as standard risk may actually harbor low-level mutations that drive relapse, potentially changing how we risk-stratify and monitor these patients in the near future.

Clinical Bottom Line

Here are the key takeaways from this week in Hematology.

First: In newly diagnosed AML, be aware that FLT3-ITD microclones, detectable only by sensitive next-generation sequencing, carry a significant risk of relapse similar to macroclones. Current risk models may need updating [5].

Second: For patients with newly diagnosed Philadelphia-negative ALL, adding venetoclax to pediatric-inspired chemotherapy appears to significantly improve MRD negativity and survival, based on promising phase 2 data [3].

Third: In your patients with sickle cell trait, a large population study provides reassurance against increased all-cause mortality or major cardiovascular events. However, you should be vigilant for an increased risk of chronic kidney disease, diabetes, and hypertension in this population [7].

Fourth: For patients with splanchnic vein thrombosis, the presence of an underlying MPN does not appear to alter the short-term risks of recurrent thrombosis, bleeding, or death, suggesting a unified anticoagulation strategy may be appropriate for many patients [1].

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.