This Week in Hematology — Jun 24, 2026

Welcome to This Week in Hematology. This week we are covering nine notable papers spanning advanced cellular therapies and precision monitoring in lymphomas, optimized treatment protocols in chronic lymphocytic leukemia and hemophilia, and novel systemic interventions in thrombosis and immunology. Let us dive in.

We begin with a milestone in cellular immunotherapy. CD19-directed chimeric antigen receptor T-cell therapy has transformed the management of relapsed or refractory B-cell non-Hodgkin lymphomas, but long-term data on its curative potential have been limited. In The New England Journal of Medicine, Ruella and colleagues present the ten-year outcomes of thirty-eight heavily pretreated patients with B-cell lymphomas, including twenty-four with large B-cell lymphoma and fourteen with follicular lymphoma, who received a single infusion of tisagenlecleucel [8]. At a median follow-up of ten point one years, the results demonstrate a true plateau in the survival curves, with absolutely no relapses occurring beyond five point four years. The ten-year lymphoma-free survival was thirty-two percent for patients with large B-cell lymphoma and forty-seven percent for those with follicular lymphoma. However, when accounting for deaths from any cause, the ten-year progression-free survival rates were seventeen percent and twenty-nine percent, while overall survival rates were seventeen percent and fifty percent, respectively. Notably, a second primary cancer developed in nine patients, representing a ten-year cumulative incidence of twenty-one percent, while the ten-year non-relapse-related mortality was eighteen percent. While these decade-long remissions confirm the curative potential of CAR T-cell therapy for a substantial subset of patients, clinicians must remain vigilant regarding late complications. Indeed, a key challenge in post-CAR T-cell care is hematologic toxicity. Writing in Blood Advances, Wudhikarn and colleagues from the Cell Therapy Consortium analyzed four hundred and forty-four patients with relapsed or refractory large B-cell lymphoma to characterize late cytopenias, defined as those persisting beyond day thirty post-infusion [6]. Grade three or higher cytopenias were remarkably common, affecting forty-seven percent of patients at one month, thirty-four percent at two months, nineteen percent at three months, twenty-one percent at six months, and eleven percent at twelve months. Neutropenia consistent with late immune effector cell-associated hematotoxicity occurred in roughly one-third of patients between days thirty and one hundred. The researchers identified a high CAR-HAEMATOTOX score of two or greater as a predictor of cytopenia at three months, whereas receiving bridging systemic chemotherapy and axicabtagene ciloleucel predicted cytopenia at six months. Crucially, the presence of late cytopenia was associated with a more than doubled rate of one-year non-relapse mortality, at eleven percent compared to four point four percent, as well as significantly worse two-year progression-free and overall survival. This highlights the urgent need for consistent, long-term hematologic monitoring and supportive care in these patients. To better identify which responding patients are at risk of relapse, we look to a meta-analysis also published in Blood Advances by Gordon and colleagues [5]. While positron emission tomography, or PET, is the standard for response assessment in large B-cell lymphoma, twenty to thirty percent of patients who achieve a metabolic response will still relapse. This meta-analysis of three hundred and sixty-seven patients treated with curative-intent frontline chemoimmunotherapy evaluated the integration of end-of-treatment circulating tumor DNA, detected by highly sensitive phased-variants, alongside PET imaging. The prognostic value of undetectable circulating tumor DNA was striking, with a hazard ratio for progression-free survival of fourteen point zero two compared to detectable circulating tumor DNA, which was substantially stronger than the hazard ratio of five point zero nine for achieving a PET complete metabolic response versus no complete response. Patients with both undetectable circulating tumor DNA and a PET complete metabolic response had an outstanding two-year progression-free survival rate of ninety-five point seven percent. In contrast, those with detectable circulating tumor DNA but a PET complete metabolic response had a two-year progression-free survival rate of only forty point two percent. These findings suggest that phased-variant-detected measurable residual disease provides powerful, independent prognostic information that could refine post-treatment surveillance and guide consolidation strategies.

Moving from post-treatment monitoring to consolidation therapy, we examine the role of post-transplant brentuximab vedotin maintenance in classic Hodgkin lymphoma. In Blood Cancer Journal, Desai and colleagues evaluated a large international real-world cohort of high-risk relapsed or refractory patients undergoing autologous stem cell transplantation to clarify the benefit of brentuximab maintenance based on pre-transplant metabolic response [1]. In patients with a partial metabolic response, brentuximab maintenance was associated with a highly significant improvement in five-year progression-free survival, reaching fifty-nine point six percent compared to forty-three percent in those without maintenance, representing a nearly halved risk of progression. In the overall subgroup of patients in complete metabolic response, brentuximab maintenance did not show a statistically significant progression-free survival benefit. However, when the investigators restricted the analysis to patients with a complete metabolic response treated after the United States Food and Drug Administration approval of brentuximab vedotin, a significant survival benefit did emerge, with a five-year progression-free survival of eighty-one point two percent in the maintenance group versus fifty-five point two percent in the non-maintenance group. This real-world evidence supports the continued use of post-transplant brentuximab maintenance in high-risk classic Hodgkin lymphoma, regardless of whether patients achieve a complete or partial metabolic response prior to transplant. In chronic lymphocytic leukemia, venetoclax-based regimens are highly effective, but their initiation is complex due to the risk of tumor lysis syndrome, which traditionally requires a meticulous five-week outpatient dose ramp-up. Crombie and colleagues, writing in Blood Advances, investigated a novel solution in the SAVE trial, a phase one-b study evaluating an accelerated, inpatient daily venetoclax escalation protocol combined with obinutuzumab [9]. Forty patients, including those with medium or high tumor lysis syndrome risk, underwent a rapid daily ramp-up from twenty milligrams to the full four hundred milligram dose over a median inpatient stay of just seven days. Remarkably, no patients experienced clinical tumor lysis syndrome. Only one patient, who had high-risk, BTK-inhibitor-refractory disease, developed laboratory tumor lysis syndrome, which resolved within twenty-four hours with a one-day dose hold and standard supportive care. The overall response rate at three months was seventy-eight percent. While this accelerated inpatient protocol requires validation in larger trials, it represents a highly promising option for rapidly initiating venetoclax in patients who cannot undergo a five-week escalation. For patients with hemophilia, non-factor-replacement therapies have revolutionized prophylactic care. In Blood Advances, Young and colleagues presented the fifty-six-week cut-off results from the phase three explorer eight study of concizumab, a once-daily subcutaneous anti-tissue factor pathway inhibitor prophylactic treatment for patients with hemophilia A or B without inhibitors [4]. Among one hundred and forty-eight patients, those receiving concizumab maintained low median annualized bleeding rates of one point seven for hemophilia A and two point eight for hemophilia B, which was highly consistent with earlier thirty-two-week data. Concizumab plasma concentrations remained stable over the fifty-six-week period, and no new safety concerns were identified, confirming that daily subcutaneous concizumab offers safe, highly effective, and sustained bleed protection.

Our final theme addresses critical systemic therapies spanning cardiovascular, cerebrovascular, and immunological health. We begin with the management of acute ischemic stroke, where successful endovascular thrombectomy does not always translate to functional independence. In The Lancet, the ATTRACTION trial investigators evaluated whether adjunctive tirofiban, a glycoprotein two-b three-a receptor antagonist, could improve outcomes when administered immediately after successful endovascular reperfusion in acute anterior-circulation large-vessel occlusion [2]. In this double-blind, randomized trial of one thousand three hundred and eighty patients across eighty-two hospitals in China, patients received either an intra-arterial bolus of tirofiban followed by a twenty-four-hour intravenous infusion, or a matching placebo. Tirofiban significantly increased the likelihood of achieving functional independence at ninety days, with forty-nine percent of patients in the tirofiban group achieving a modified Rankin Scale score of zero to two compared to forty-three percent in the placebo group. Symptomatic intracranial hemorrhage within forty-eight hours occurred numerically more often with tirofiban, at twelve percent versus nine percent, though this difference did not reach statistical significance, and there was no difference in ninety-day mortality. Clinicians must carefully weigh this absolute six percentage point gain in functional independence against the potential bleeding risk when considering adjunctive tirofiban post-thrombectomy. In the realm of pediatric immunology, the prevention and management of peanut allergy has undergone a paradigm shift. A review in The New England Journal of Medicine by Du Toit and Lack emphasizes that the early introduction of peanut protein in infancy reduces the prevalence of peanut allergy by approximately eighty percent, with efficacy rapidly diminishing as introduction is delayed [7]. For low-risk infants, a weekly ingestion of approximately two grams of peanut protein is recommended, while high-risk infants require four to six grams weekly. The authors stress that population-level implementation targeting all infants yields a far greater reduction in disease burden than high-risk screening, and that peanut immunotherapy initiated in children aged one to three years achieves superior rates of clinical remission compared to older cohorts. Finally, we look at a novel cardiovascular therapy that addresses a major comorbidity in hematology and oncology populations: heart failure with reduced ejection fraction. Existing inotropic therapies are often limited by significant adverse effects. In The Lancet, Lund and colleagues reported results from the GOAL-HF one trial, a phase one-b two-a randomized, double-blind, placebo-controlled study of AC01, a novel oral calcium-sensitizing inotrope and ghrelin receptor agonist [3]. Fifty-eight patients with stable heart failure and an ejection fraction of forty percent or lower, all of whom had an implantable cardioverter defibrillator, were randomized to ascending doses of AC01 or placebo. The therapy was well tolerated with no drug-related serious adverse events. Mild or moderate adverse events occurred in eighty percent of the AC01 group and seventy-one percent of the placebo group, with the most common events being hypotension, non-sustained ventricular tachycardia, dyspnea, hyperglycemia, dizziness, and headache, without any signs of new-onset tachyarrhythmias or myocardial ischemia on continuous electrocardiogram monitoring. This study establishes a safe foundation for further efficacy trials of this novel inotropic mechanism.

If you only have time for one paper this week, make it the ten-year follow-up of tisagenlecleucel for B-cell lymphomas published in The New England Journal of Medicine [8]. This landmark study provides the longest prospective follow-up to date for CD19-directed CAR T-cell therapy, confirming that a single infusion can lead to decade-long, treatment-free remissions in approximately one-third of patients with large B-cell lymphoma and nearly half of those with follicular lymphoma, while simultaneously highlighting critical long-term risks like second primary malignancies that require lifelong surveillance.

Here are the key takeaways from this week in Hematology. First, a single infusion of tisagenlecleucel offers durable, decade-long remissions for relapsed or refractory B-cell lymphomas, but patients require long-term monitoring for late toxicities, including a twenty-one percent cumulative incidence of second primary cancers at ten years. Second, late cytopenias beyond day thirty post-CAR T-cell therapy are common and clinically significant, carrying a more than doubled risk of non-relapse mortality and worse overall survival, with high-risk patients identifiable via the CAR-HAEMATOTOX score. Third, circulating tumor DNA detected by phased-variants at the end of frontline therapy in large B-cell lymphoma is a highly powerful prognostic marker that outperforms PET imaging and can identify patients at high risk of relapse despite achieving a complete metabolic response. Fourth, post-transplant brentuximab maintenance significantly improves five-year progression-free survival in high-risk classic Hodgkin lymphoma, with clear benefits demonstrated in patients with a partial metabolic response and those in complete metabolic response treated in the modern era. Finally, in chronic lymphocytic leukemia, an accelerated daily inpatient venetoclax ramp-up over seven days is clinically feasible and safe, offering a rapid alternative to the standard five-week protocol for select patients.

That is 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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