Secondary and idiopathic polycythaemia is far more common than polycythaemia vera. Whilst venesection for polycythaemia vera has a robust evidence base, the data supporting this treatment for secondary and/or idiopathic polycythaemia are limited to small single-arm studies showing transient improvement in symptoms or physiologic endpoints. As a result the British Society for Haematology Guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis suggests considering venesection in patients with hypoxic lung disease with Hct > 0.56 or to a target Hct < 0.55 in those with idiopathic polycythaemia. We hypothesised that this paucity of evidence results in widespread variation in management of secondary polycythaemia.
To assess attitudes and practice in the treatment of secondary and idiopathic polycythaemia we designed an international clinician survey to evaluate current practice and define the point of clinical equipoise at which clinicians would be content to enter patients into a randomised venesection study. This survey was distributed using the wide-reaching HaemSTAR research network.
A total of 123 clinicians responded, of which 90 were experienced senior clinicians. 62% reported not routinely offering regular venesection whereas 38% of respondents did. Those considering venesection rose to ∼2/3 of respondents in specific circumstances such as polycythaemia-related symptoms, previous arterial or unprovoked venous thrombosis. Respondents were more likely to offer venesection to patients with idiopathic- compared to androgen- or hypoxia-driven polycythaemia. Of those who would venesect, most would use a threshold Hct ≥ 0.55, with a target Hct < 0.55 but there was significant variability.
Our survey showed considerable variability in venesection practice for patients with secondary or idiopathic polycythaemia, probably reflecting the paucity of the evidence base. There was widespread support for a trial of venesection vs observation in secondary polycythaemia and this survey has helped to define the threshold Hct at which clinical equipoise exists.
Patients with relapsed/refractory post-transplant lymphoproliferative disorder (R/R PTLD) following solid-organ transplants (SOT) or hematopoietic stem cell transplants (HSCT) after frontline chemoimmunotherapy have dismal outcomes. There is no standard of care for this group of patients, and they are generally excluded or ineligible for clinical trials. Several effective novel agents have been licensed in recent years for the treatment of diffuse large b-cell lymphoma (DLBCL), including CD19 CAR-T cell therapy and CD3xCD20 bispecific antibody.
Acknowledging the limited data and extrapolating the evidence from trials in DLBCL, we report a case of R/R PTLD successfully treated with CD3xCD20 bispecific antibody, Epcoritamab, with good tolerability and long-term response.
The authors have confirmed clinical trial registration is not needed for this submission.
IgA-mediated autoimmune hemolytic anemia (AIHA) is a rare condition associated with severe hemolysis and limited therapeutic response. Bortezomib, a proteasome inhibitor, targets plasma cells responsible for autoantibody production. Here, we describe a case of refractory IgA-mediated AIHA in a 13-year-old boy presenting with severe hemolysis, who was successfully treated with bortezomib.
Blood samples were collected at different time points throughout the disease course for immunohematology testing.
The patient showed significant hematologic improvement following four doses of Bortezomib with reduction in hemolysis and recovery of hemoglobin levels. Laboratory tests revealed complement-negative, Coombs-positive blood tests combined with altered RBC morphology. Phagocytosis of patient's RBC was absent at all timepoints. Notably, despite hematologic improvement, IgA-positive RBC remained present, accompanied by compensated hemolysis.
The present case demonstrates the potential of bortezomib as a treatment option for refractory AIHA cases, particularly in children.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission
Aggressive non-Hodgkin lymphoma (aNHL) often relapses after first-line treatment. Clinical data supports the safety and efficacy of the combination of mosunetuzumab, a CD20×CD3 bispecific antibody, and polatuzumab vedotin, an anti-CD79b antibody drug conjugate (Mosun-Pola) in relapsed/refractory aNHL. This study investigated the molecular mechanism behind the combination effect of Mosun-Pola in human diffuse large B-cell lymphoma (DLBCL) cell lines.
The in vitro Mosun-Pola efficacy in DLBCL cells (SU-DHL-8 and HT) was evaluated by T cell-dependent cellular cytotoxicity (TDCC) assay. CD20-stable-knockdown SU-DHL-8 cells were established using lentiviral short hairpin RNA. Surface and T-cell activation marker proteins expression were determined by flow cytometry. Human T-cell-injected mice or humanized NOD/Shi-scid, IL-2Rγnull (huNOG) mice were used for an in vivo study.
An in vitro TDCC assay showed a synergistic effect in SU-DHL-8 and HT cells. Based on our experimental results of suppressing CD20 expression, it was suggested that this combination effect could be caused by an increase in CD20 expression by polatuzumab vedotin. In addition, examining the effects of CD20 upregulation in tumor cells on T-cell activation demonstrated that the combination of Mosun-Pola enhanced T-cell activation markers in both CD4+ and CD8+ T cells during the TDCC reaction. In vivo studies, using human immune system-reconstituted mouse models confirmed that polatuzumab vedotin enhanced CD20 expression in tumors, and the combination of Mosun-Pola showed significantly improved anti-tumor effects compared with single-drug treatments.
These findings suggest that polatuzumab vedotin-induced CD20 upregulation provides a molecular rationale to explain the synergistic effect of this combination therapy.
The authors have confirmed clinical trial registration is not needed for this submission.
A. Alraddadi, J. P. Smalley, W. Alzahrani, et al. “Targeted Degradation of Class 1 HDACs With PROTACs is Highly Effective at Inducing DLBCL Cell Death,” EJHaem 6, no. 4 (2025): e70127, https://doi.org/10.1002/jha2.70127.
Co-author Martin J. S. Dyer was incorrectly listed as Martin Dyer.
We apologize for this error.
NUP98::BPTF rearranged (r) leukaemia is rare with only five reported cases, including acute myeloid leukemia and T-lymphoblastic leukemia (T-ALL).
Herein, we report a case of NUP98::BPTF-r mixed phenotype acute leukemia (MPAL), B/T with T-lineage-predominance in a 15-year-old female. Cytogenetic and molecular studies revealed a t(11;17)(p15;q23)/NUP98::BPTF fusion and cooperative gene alterations characteristic of T-ALL (NOTCH1, FBXW7, and PHF6). Our patient had a primary induction failure with T-ALL-directed chemotherapy and achieved complete remission following consolidation.
This is the first case study characterizing the clinicopathological and genomic features of B/T MPAL harboring NUP98::BPTF fusion and providing insights into molecular pathogenesis.
The authors have confirmed clinical trial registration is not needed for this submission.
The emergence of JAK2-mutated myeloproliferative neoplasms (MPNs) after remission from acute myeloid leukaemia (AML) is exceedingly rare.
This case series describes two patients who developed JAK2-mutated MPNs years after achieving AML remission, each retaining persistent TET2 and SRSF2 mutations while losing AML-defining mutations.
Findings support clonal persistence from a shared haematopoietic progenitor with divergent progression into distinct myeloid neoplasms. A two-pathway model is proposed to explain this trajectory.
These observations highlight the biological relevance of CHIP-associated mutations and underscore the value of post-remission molecular surveillance to detect emerging secondary neoplasms in AML survivors.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
Measurable residual disease (MRD) is a strong predictor of the risk of relapse of acute myeloid leukemia (AML). Therefore, for use in clinical decision-making, methods for MRD assessment must achieve adequate accuracy, sensitivity, specificity, and reproducibility. Multiparametric flow cytometry (MFC) is the most widely used method for assessing AML-MRD, but its sensitivity varies considerably due to the differing approaches used across centers, in addition to the different experiences of flow cytometrists, especially during clonal evolution. This study aimed to standardize AML-MRD by MFC in a multicenter project involving 16 Brazilian laboratories.
In the first phase, specialists were trained in pre-analytical standard operating procedures (SOPs) and analysis strategies of pre-validated 8- and 10-color protocols, followed by a data-only, that is, a Dry Phase of flow cytometry standard (FCS) file exchange by the coordinating laboratory in a comparability assessment. In the second or Wet Phase, laboratories prepared and analyzed their samples, and the FCS files were submitted for central analysis.
The agreement of MRD results was 81% and 80% between laboratories and central analysts in the Dry and Wet Phases, respectively. However, non-suitable application of pre-analytical SOPs hampered MRD interpretation for 30% of the laboratories in the Wet Phase.
This study demonstrated that standardized flow cytometry protocols are reproducible as long as rigorous SOPs are implemented. The project's results underscore that continuous education and external quality control are essential to build expertise and ensure reliable AML-MRD results in clinical practice.
Trial Registration:The authors have confirmed clinical trial registration is not needed for this submission.
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