This Week in Hematology — Jul 1, 2026

Welcome to This Week in Hematology. This week we are covering ten notable papers spanning three major areas: myeloid malignancies including myelofibrosis, myelodysplastic syndromes, and acute myeloid leukemia; lymphoid neoplasms featuring chronic lymphocytic leukemia, acute lymphoblastic leukemia, and classic Hodgkin lymphoma; and key updates in benign hematology, thrombosis, and bleeding disorders. Let's dive in.

We begin in the realm of myeloid malignancies, where clinical trials are testing novel combinations to improve responses, though often at the cost of increased toxicities. In the phase three TRANSFORM-1 study published in Blood, researchers evaluated adding the BCL-2 and BCL-XL inhibitor navitoclax to ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis who had not previously received a Janus kinase inhibitor [1]. Among 252 patients, the combination of navitoclax and ruxolitinib roughly doubled the rate of spleen volume reduction of 35% or more at week 24, achieving this in 63% of patients compared to 31.5% with ruxolitinib alone. Spleen response at any time was also higher, at nearly 77% versus 44%. However, this did not translate into a significant difference in symptom burden; the change in the Total Symptom Score at week 24 was not statistically different between the groups. Furthermore, navitoclax was associated with substantial hematologic toxicity, including a nearly threefold increase in grade 3 or 4 thrombocytopenia, at 54% versus 19%, and a more than fourfold increase in grade 3 or 4 neutropenia, at 40% versus 9%. Diarrhea was also more common. While these cytopenias were manageable and reversible with dose adjustments, clinicians must weigh the superior spleen response against the lack of symptom benefit and the added toxicities.

Continuing with combination strategies, a large real-world analysis from the International Consortium for MDS VALIDATE database, published in Blood Cancer Journal, examined the addition of venetoclax to hypomethylating agents in frontline higher-risk myelodysplastic syndromes [2]. This analysis of over 1,900 patients is particularly timely given that the randomized phase three VERONA trial recently showed no overall survival benefit for adding venetoclax to azacitidine. In this database, adding venetoclax significantly improved the composite complete remission rate from 28% to nearly 49%. However, the true complete remission rate was not significantly different, and there was no statistically significant overall survival benefit for the combination across the entire cohort. Crucially, subgroup analyses revealed that patients with TP53 wild-type disease experienced a significant improvement in overall survival, with the hazard ratio for death dropping to 0.47, and there was a strong trend toward survival benefit in patients with 10% or more bone marrow blasts. These findings suggest that while a universal combination strategy is not warranted, a targeted approach prioritizing patients with TP53 wild-type status or higher blast counts could yield meaningful survival advantages.

In acute myeloid leukemia, we have two important updates. First, the PETHEMA group published results from the FLAG-QUIDA trial in the American Journal of Hematology, a phase one/two study evaluating the FLT3 inhibitor quizartinib combined with intensive FLAG-IDA chemotherapy for patients with their first relapsed or refractory acute myeloid leukemia [8]. The recommended phase two dose of quizartinib was established at 60 milligrams per day for 14 days of a 28-day cycle. Among 61 patients, the combination produced a complete remission or complete remission with incomplete hematologic recovery rate of 56%, which rose to 66% when including patients who achieved a morphologic leukemia-free state. This high rate of response allowed over half of the cohort to be successfully bridged to an allogeneic stem cell transplant. Patients treated with the quizartinib combination had a median relapse-free survival of 17 months, compared to 7.6 months in a matched historical cohort treated with FLAG-IDA alone. Although the median overall survival of nearly 16 months did not reach statistical significance compared to the 8.6 months in the matched cohort, the safety profile was manageable with no new safety concerns. Meanwhile, a study in Blood Cancer Journal explored the clonal dynamics of IDH1 and IDH2 mutations in acute myeloid leukemia [10]. The researchers demonstrated that the persistence and fluctuation of these mutated clones challenge their utility as universal markers for measurable residual disease. Because pre-leukemic clones carrying IDH mutations can persist in the bone marrow during complete morphologic remission without predicting imminent relapse, the authors advise that clinicians should not rely on IDH mutational status alone to define measurable residual disease or to guide post-remission therapeutic decisions.

We now turn to lymphoid malignancies, where the focus is shifting toward personalized, measurable residual disease-driven treatment. In Blood Advances, investigators published the long-term follow-up of the phase two trial evaluating the BOVen triplet regimen of zanubrutinib, obinutuzumab, and venetoclax in treatment-naive chronic lymphocytic leukemia [4]. Using an innovative, MRD-driven treatment design, the study aimed to optimize the duration of therapy to minimize toxicities. With a median observation time of nearly 69 months and a median treatment duration of only 10 cycles, 96% of patients achieved undetectable measurable residual disease at the 10-to-the-minus-4 threshold in the blood, and 92% achieved this in both blood and bone marrow. The 48-month progression-free survival was nearly 80%, and the regimen was well-tolerated, with a 25% rate of grade 3 or 4 neutropenia and a low 9.6% rate of infections. A key finding was that a 400-fold or greater reduction in blood MRD at four months, termed delta-MRD400, successfully identified patients who achieved earlier bone marrow clearance and experienced significantly longer MRD-free survival, despite receiving a shorter duration of therapy. This biomarker is currently being evaluated in prospective trials to guide the duration of venetoclax- and sonrotoclax-based triplets, offering a path toward personalized, time-limited therapy.

In B-cell acute lymphoblastic leukemia, a phase two study published in Blood Cancer Journal evaluated the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin to eradicate detectable measurable residual disease in adults who were in morphologic remission [3]. Among 37 patients, 70% achieved complete MRD negativity, with high rates of clearance in both Philadelphia-chromosome-negative and Philadelphia-chromosome-positive disease. Over a median follow-up of 50 months, the median overall survival was 61 months, and the median relapse-free survival was 40 months. Crucially, patients who received inotuzumab during their first morphologic remission had a median overall survival that was not reached, compared to only 14 months for those treated in their second or subsequent remission, highlighting the importance of early, aggressive MRD eradication. The therapy was generally well-tolerated, although three cases of non-fatal sinusoidal obstructive syndrome were observed, reinforcing the need for close hepatic monitoring.

In classic Hodgkin lymphoma, the German Hodgkin Study Group published a validation study in Blood Advances regarding the newly refined Deauville Score [9]. The Lugano Imaging Committee recently subdivided Deauville Score 5 into 5a, defined as more than twice the liver uptake without new lesions, and 5b, representing new lesions. Analyzing data from several GHSG trials including HD18 and HD21, the researchers confirmed that while a Deauville Score of 5a at interim PET after two cycles of chemotherapy is relatively rare, occurring in only 4 to 6% of patients, it is a highly adverse prognostic marker. In the primary cohort of patients treated with eBEACOPP, a score of 5a was associated with a threefold increased risk of disease progression compared to scores of 1 to 3, and more than double the risk compared to scores of 1 to 4. This study provides the first prospective validation of this refined scoring system, confirming that Deauville Score 5a successfully isolates a very small, high-risk population of patients with advanced-stage classic Hodgkin lymphoma who may benefit from early, risk-adapted treatment adaptation.

Our final theme covers benign hematology, providing practical insights for daily clinical practice. In Blood Advances, researchers utilized data from the large RIETE registry to analyze the presentation, management, and outcomes of over 2,700 women under the age of 50 who experienced acute venous thromboembolism while on estrogen therapy [6]. When compared to men and other women of similar age, women with estrogen-associated thrombosis were younger, with a mean age of 32, and the vast majority had no additional transient risk factors. Estrogen therapy was discontinued in 92% of cases at the time of diagnosis, and patients were treated with anticoagulation for a median of six months. The study revealed two critical findings: first, during active anticoagulation, women with estrogen-associated events experienced high rates of bleeding, driven primarily by heavy uterine bleeding. Second, after stopping anticoagulation, the risk of recurrent thrombosis in the first year was remarkably low at just over 2% per 100 patient-years, which was significantly lower than the recurrence rates of nearly 9% in men and 5% in other women. This suggests that while a standard course of anticoagulation is highly effective and recurrence risk is low once therapy is stopped, clinicians must proactively manage and support patients regarding the risk of heavy menstrual bleeding during active treatment.

In the field of bleeding disorders, a study in Blood resolved a long-standing clinical and laboratory dilemma in hemophilia A gene therapy [7]. When monitoring patients treated with adeno-associated virus gene therapy delivering a B-domain-deleted factor VIII, the one-stage clotting assay consistently yields activity values that are one and a half to two times higher than those obtained with the chromogenic substrate assay. By comparing gene-therapy-derived factor VIII to recombinant factor VIII in both mouse models and participants from the SPK-8011 clinical trial, researchers discovered that this discrepancy is driven by enhanced thrombin-mediated activation of the gene-therapy-derived factor VIII. This enhanced activation is fully captured by the one-stage assay but missed by the chromogenic assay. Crucially, the one-stage assay activity levels better correlated with actual in vivo hemostatic function and trended toward a better prediction of the annualized bleeding rate. This provides strong reassurance to hematologists that the one-stage assay is the most physiologically relevant and clinically predictive tool for managing these patients.

To round out our benign hematology updates, the British Journal of Haematology published expert guidance on the diagnosis and management of neutropenia in adults [5]. The authors reinforce the standard absolute neutrophil count threshold of 1.8 times 10 to the ninth per liter for defining neutropenia in Caucasian adults, while emphasizing that normal thresholds can vary significantly based on age and ethnic origin. The guidance provides a structured diagnostic framework to differentiate inherited and congenital causes from acquired forms, such as drug-induced or autoimmune neutropenia. It also outlines the appropriate clinical use of granulocyte colony-stimulating factor to manage severe chronic neutropenia and prevent life-threatening infections, and introduces a dedicated transition program to support adolescent patients as they move into adult hematology care.

If you only have time for one paper this week, make it the long-term follow-up of the BOVen trial in chronic lymphocytic leukemia, published in Blood Advances [4]. This study is a major step forward for personalized hematology, demonstrating that an MRD-driven, time-limited triplet regimen can achieve durable, deep remissions with a median of only ten months of therapy, while introducing a highly practical four-month blood biomarker to safely guide treatment duration in daily practice.

Here are the key takeaways from this week in Hematology. First, in untreated myelofibrosis, adding navitoclax to ruxolitinib significantly increases spleen volume reduction but does not improve symptom scores at 24 weeks, and it carries a high burden of hematologic toxicity [1]. Second, while adding venetoclax to hypomethylating agents does not improve overall survival for all higher-risk MDS patients, it offers a substantial survival benefit for those with TP53 wild-type disease [2]. Third, in B-cell acute lymphoblastic leukemia, using inotuzumab ozogamicin to target detectable MRD in morphologic remission is highly effective, especially when initiated during the first remission [3]. Fourth, for young women with estrogen-associated venous thromboembolism, the risk of recurrence after completing a standard course of anticoagulation is very low, but they face a high risk of uterine bleeding during active treatment [6]. And finally, when monitoring patients after hemophilia A gene therapy, the one-stage factor VIII clotting assay is the most reliable predictor of hemostatic function and clinical bleeding risk [7].

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.

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