This Week in Hematology — Sep 9, 2026

Welcome to This Week in Hematology. This week we're covering 10 notable papers spanning risk stratification across myeloid and plasma cell disorders, salvage and supportive strategies in acute leukaemia and bone marrow failure, and a set of papers that ask us to rethink diagnostic thresholds — from haemoglobin cut-offs to how we biopsy for amyloid. Let's dive in.

Let's start with acute myeloid leukaemia, where two papers approach the same disease from very different angles. In the British Journal of Haematology, Dumas and colleagues report a real-world comparison from the DATAML-IPC-AURAML consortium of salvage therapy for adults in first relapse after intensive chemotherapy — just over two hundred patients treated with intermediate or high-dose cytarabine regimens against 114 given venetoclax plus azacitidine [1]. Second complete remission rates were essentially identical, about two thirds in each arm, and relapse-free and overall survival were statistically indistinguishable at roughly twelve to fourteen months. What makes this useful clinically is the interaction they found on multivariable analysis: patients aged sixty and over with low or intermediate-risk cytogenetics did better with venetoclax-azacitidine, whereas younger patients with poor-risk cytogenetics did better with cytarabine-based salvage. This is retrospective and non-randomised, so it should not replace clinical judgement, but it supports what many of us already do — reserve intensive salvage for the young, biologically adverse patient who needs rapid cytoreduction to transplant, and consider the doublet for older patients with more favourable cytogenetics. Complementing that, Blood Advances published a prospective multicentre genomic study by Kim and colleagues of 603 adults with newly diagnosed acute myeloid leukaemia in Korea, benchmarked against the Beat AML cohort [8]. The core architecture was broadly conserved, but core-binding factor rearrangements, CEBPA, GATA2, KIT and DDX41 mutations were all more frequent in the Korean cohort, while FLT3 and NPM1 were less common. That shifts the distribution across European LeukemiaNet 2022 risk categories in a way that has direct therapeutic consequences. The practical message is DDX41: about three percent of patients carried alterations that were mostly germline, which matters for genetic counselling and, critically, for related donor selection. The apparent survival advantage in the Korean cohort disappeared once clinical variables were accounted for.

Moving to plasma cell disorders, where two papers tackle risk stratification and a third addresses diagnosis. In Leukemia, Li and colleagues asked whether circulating tumour cells add anything to the new 2025 International Myeloma Society and International Myeloma Working Group consensus genomic staging system [4]. Across more than six hundred patients from the NICHE cohort, circulating tumour cells were detectable in roughly two thirds of newly diagnosed patients, and a threshold of about 0.4 percent independently predicted shorter progression-free survival. The interesting finding is where it added value — specifically within the genomic high-risk group, where patients who were also circulating tumour cell-high had the shortest progression-free survival. That defines what the authors call a disseminated genomic high-risk phenotype in about one in eight evaluable newly diagnosed patients, and it is identifiable from peripheral blood. Circulating tumour cells also tracked outcomes during non-progressive disease and added information alongside bone marrow minimal residual disease. Set against that, the British Journal of Haematology published a Japanese real-world evaluation by Nakayama and colleagues of the UK Myeloma Research Alliance risk profile in nearly eight hundred transplant-ineligible patients [5]. The score held up well overall — high-risk patients had roughly two and a half times the mortality of low-risk patients — and it discriminated survival in those treated with bortezomib-based and lenalidomide-based regimens. But here is the flag: among patients receiving daratumumab-based therapy, the risk groups no longer separated at all. That is a genuine caution about applying clinical prognostic scores built in a pre-anti-CD38 era to today's front-line practice, and it contrasts instructively with the circulating tumour cell work, where the biology-based marker retained discriminating power. On the diagnostic side, Blood Advances carried a systematic review and meta-analysis by Azzam and colleagues of thirty-one studies assessing fat pad sampling and bone marrow biopsy for light-chain amyloidosis against organ biopsy [7]. Pooled sensitivity for abdominal fat pad sampling was about 77 percent with moderate certainty evidence, while bone marrow biopsy came in at only about 55 percent with low certainty. Aspiration and surgical or punch biopsy performed similarly, and a single large study found combining fat pad and marrow raised sensitivity to about 89 percent. Because every included study enrolled patients with confirmed disease, specificity could not be assessed. The take-home is that a negative fat pad aspirate — and certainly a negative marrow — does not exclude amyloidosis, and roughly a quarter of patients will need organ biopsy to secure the diagnosis.

Our third theme concerns clonal biology, age, and long-term surveillance. Also in Leukemia, Tian and colleagues followed 371 patients with aplastic anaemia through immunosuppressive therapy, with serial targeted sequencing in 237 of them [6]. Somatic mutations were present in about a fifth of patients at baseline and rose to roughly two fifths after treatment, most commonly through newly acquired clones. The dynamics were not uniform: high-risk mutations such as ASXL1 expanded persistently, whereas BCOR and PIGA clones tended to contract or stay stable. Cytogenetic abnormalities roughly doubled from about five to ten percent of patients, paroxysmal nocturnal haemoglobinuria clones stayed relatively stable with fifteen patients progressing to overt PNH syndrome, and six patients evolved to a myeloid neoplasm. The clinical implication is straightforward — detecting a clone after immunosuppression is common and is not in itself a reason to abandon course, but the specific gene matters, and long-term molecular surveillance is warranted. On a related theme of age as a biological modifier, the British Journal of Haematology published a Chinese multicentre study by Li and colleagues of 1,728 patients with essential thrombocythaemia across 29 centres, comparing adolescents and young adults aged fifteen to thirty-nine against those forty and older [9]. Younger patients had fewer cardiovascular risk factors and less thrombosis despite more extreme thrombocytosis, were enriched for CALR mutations rather than JAK2, and carried a lower burden of non-driver mutations such as TET2, DNMT3A and ASXL1. They did better across overall, myelofibrosis-free and leukaemia-free survival. But CALR mutation showed an age-specific association with progression to post-essential thrombocythaemia myelofibrosis in the young — so a favourable overall prognosis should not translate into casual follow-up for the young CALR-mutant patient.

Finally, two papers on the harder edges of practice. Journal of Thrombosis and Haemostasis reports preclinical work by Xue and colleagues on fusion constructs that link a truncated, autoantibody-resistant ADAMTS13 to a single-domain antibody directed at the active conformation of von Willebrand factor's A1 domain [10]. The dual-action construct retained strong proteolytic activity, reduced platelet-von Willebrand factor interaction in solution without impairing platelet adhesion to collagen-bound von Willebrand factor, and showed superior resistance to patient autoantibodies. This is bench work, not a clinical trial, but it points to a plausible successor strategy to caplacizumab plus recombinant ADAMTS13 in immune thrombotic thrombocytopenic purpura. And in Blood, Weaver and colleagues offer a How I Treat piece on paediatric haematology-oncology patients from families identifying as Jehovah's Witnesses [2]. Their central point is that transfusion avoidance should never be presumed — preferences are heterogeneous, shaped by individual conscience and interpretation, and worth exploring in depth rather than assumed. Through three cases they walk through emerging adolescent autonomy, intrafamilial disagreement in an infant with severe aplastic anaemia, the thresholds at which pre-emptive court orders become appropriate, and concrete blood conservation and anaemia mitigation strategies.

Tying the diagnostic thread together, Annals of Internal Medicine published a prospective cohort analysis by Ahmad and colleagues of nearly half a million United Kingdom Biobank adults followed for a median of almost fourteen years, examining haemoglobin and mortality [3]. The relationship was U-shaped, with the lowest mortality at haemoglobin concentrations one to three grams per decilitre above the current World Health Organization anaemia thresholds. Participants more than two grams below threshold had roughly a threefold higher risk of death, with ten-year mortality of about twelve and a half percent versus four and a half percent in the reference group. Even patients sitting just zero to one gram above the threshold — technically not anaemic — had a modest but clear excess risk. Associations were less consistent in women under sixty. The authors are explicit that this is hypothesis-generating and should not redefine thresholds, but it is a reminder that a borderline-normal haemoglobin is not always a reassuring one.

If you only have time for one paper this week, make it the venetoclax-azacitidine versus cytarabine salvage comparison in the British Journal of Haematology [1]. It addresses a decision most of us face without randomised data, and it gives an age-and-cytogenetics framework you can apply at the bedside on Monday.

Here are the key takeaways from this week in Hematology. In first-relapse acute myeloid leukaemia, venetoclax-azacitidine matched cytarabine-based salvage overall, with older, better-cytogenetic-risk patients favouring the doublet and younger, poor-risk patients favouring intensive chemotherapy. Population-specific genomic architecture matters — the higher frequency of germline DDX41 in the Korean cohort is a direct prompt for germline testing and careful donor selection. In myeloma, circulating tumour cells refine the new consensus genomic staging within the high-risk group, while a clinical risk score built before anti-CD38 therapy lost its discriminating power in daratumumab-treated patients. A negative fat pad or bone marrow biopsy does not exclude light-chain amyloidosis; sensitivity is roughly three quarters and just over half respectively. And clonal evolution after immunosuppression for aplastic anaemia is common but gene-specific — ASXL1 expands, BCOR and PIGA often do not — so surveillance should be long-term and interpreted by mutation, not by mere presence of a clone.

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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