Light chain amyloidosis is a hematological disease requiring rapid diagnosis and urgent therapeutic intervention. The confirmation of the clinical suspicion demands invasive methods, in order to demonstrate histological involvement of organs. Substantial efforts are required especially for cardiac localization, because of mimicking conditions and non-specific symptoms. Florbetaben PET is an emerging powerful tool for early and non-invasive diagnosis and for detection of atypical sites of deposits. The present paper reports the case of a 72-year-old man diagnosed with light chain amyloidosis with cardiac and thyroid involvement early identified through this promising imaging technique.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of hematopoietic stem cell transplantation (HSCT) and is typically driven by immunosuppression and Epstein-Barr virus infection. This study analyzed the clinicopathological spectrum and outcomes of PTLD in a large single-center cohort. We retrospectively reviewed 37 PTLD patients who were diagnosed post-HSCT (2017-2024). Histopathological classification was conducted in accordance with the 5th Edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO-HAEM5). Immunohistochemistry, EBV-encoded RNA in situ hybridization, fluorescence in situ hybridization, and clonality assays were performed. Clinical data, treatment responses, and survival outcomes were collected and analyzed. The PTLD incidence was 2.4% among allo-HSCT recipients, with a male predominance (2.36:1). The median time to onset post-HSCT was 3 months (range: 1-21 months), with 81.1% of cases occurring within 6 months. The pathological types of PTLD included hyperplasias (9 cases), polymorphic PTLD (20 cases), and lymphoma (8 cases; all diffuse large B-cell lymphomas). First-line management include reduced immunosuppression, rituximab, and antiviral therapy. Prebiopsy rituximab in 5 patients caused CD20 loss, complicating the diagnosis. The mortality rate was 27%, primarily from infectious complications following PTLD-directed therapy. The median postdiagnosis survival was 3.5 months. PTLD post-HSCT is a serious complication that often follows an aggressive clinical course. While the direct contribution of PTLD to mortality was challenging to establish, its development frequently triggered intensive interventions (e.g., rituximab and immunosuppression reduction), which in turn led to fatal infectious complications in more than one-quarter of our cohort. Therefore, the high mortality in these patients was largely indirect and attributable to treatment-related infectious complications in profoundly immunocompromised hosts.

CD20 antigen loss after anti-CD20-based therapy is a mechanism of immune escape in diffuse large B-cell lymphoma (DLBCL). Emerging real-world data have shown that patients with undetectable CD20 expression who are treated with CD20-targeting bispecific antibodies may have inferior outcomes. Herein, we report a 77-year-old female patient with primary cardiac DLBCL who exhibited cardiac tamponade. The patient's CD20 expression was weak based on immunohistochemistry but was clearly positive on flow cytometry (79.2%) upon diagnosis. She received dose-reduced rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, followed by polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone. However, she developed primary refractory disease with recurrent cardiac tamponade and embolic cerebral infarction, with near-complete loss of CD20 expression according to both immunohistochemistry and flow cytometry (0.1%) on rebiopsy. The patient was not eligible for autologous stem cell transplantation and chimeric antigen receptor T-cell therapy as she personally refused blood transfusions. After one cycle of salvage gemcitabine, carboplatin, and dexamethasone, epcoritamab therapy was initiated. Catecholamine support was discontinued on day 16 of cycle 1, and hemodynamic stability was achieved on day 22. Pericardial effusion completely resolved by the end of cycle 1. Epcoritamab has been continued for > 8 months without significant adverse events, and the patient remains in computed tomography scan confirmed complete remission. Based on this case, epcoritamab may retain clinically significant activity despite undetectable CD20 expression, and CD20 negativity alone should not automatically preclude its use in refractory DLBCL.

To investigate the novel genetic mutations and clinical characteristics in a patient with MYH9 related disease in order to enhance understanding of the disease. Clinical information was obtained, including medical history, pertinent laboratory tests, and family history. Whole exome sequencing (WES) was conducted on the patient and her parents. A 19-year-old female presented with a history of epistaxis and chronic thrombocytopenia. Her aunt and brother also have a history of thrombocytopenia. Sequencing analysis revealed mutations of MYH9 gene (c.5765 + 2T > G) and HBB gene (c.126_129del) in the patient, with the c.5765 + 2T > G mutation being previously unreported. The splice site mutation of MYH9 was predicted to be pathogenic by Mutation Taster and Polyphen software programs. As a result of identifying this splicing site mutation in this particular case, we have added c.5765 + 2T > G to the broad spectrum of potential MYH9 mutations.

Patients with JAK2‑mutated MPN may develop clonal T‑cell expansions, but the prevalence, immunophenotypic spectrum, and association with other lymphoid clones remain poorly defined. Clonal T‑large granular lymphocyte (T‑LGL) expansions have been observed in myeloproliferative neoplasms (MPN), but systematic data comparing different MPN driver mutations are lacking. This retrospective study of 354 MPN patients (182 BCR::ABL[+], 163 JAK2[+], 9 CALR[+]) evaluated the prevalence and immunophenotypic features of clonal T‑LGL, and examined their co‑occurrence with monoclonal B cells and plasma cells. We retrospectively analyzed flow cytometry and molecular data from 354 consecutive MPN patients between January 2021 and April 2026. Clonal T‑LGL were identified by T-cell receptor beta chain constant region 1 (TRBC1) restriction (> 85% or < 15%) with LGL phenotype (CD3[+]CD57[+] or CD3[+]CD56[+]). Clonal burden, CD4/CD8 subset, CD5/CD7 expression, CD56/CD57 positivity, and coexisting monoclonal B or plasma cells were analyzed. Clonal T‑LGL were detected in 34 of 354 MPN patients (overall detection rate 9.6%). Detection rates were 17.2% (28/163) in JAK2[+] patients, 3.3% (6/182) in BCR::ABL[+] patients, and 0 in CALR[+] patients (JAK2[+] vs. BCR::ABL[+]: χ[2] = 18.45, P < 0.001). Among the 28 JAK2[+] cases, CD8[+] T‑LGL accounted for 71.4% (20/28), CD4[+] for 14.3% (4/28), CD4[ - ]CD8[ - ]for 10.7% (3/28), and TCRγδ[+] for 3.6% (1/28). TRBC1‑restriction showed decreased expression (< 15%) in 60.7% (17/28) and increased (> 85%) in 39.3% (11/28). CD5 downregulation/loss was observed in 57.1% (16/28) and CD7 downregulation/loss in 46.4% (13/28). CD56/CD57 positivity were 35.7% (10/28) and 78.6% (22/28), respectively. Notably, the majority of CD8[+] T-LGL clones also expressed CD57, representing the predominant immunophenotype. In the JAK2[+] group, 2 patients (7.1%) had concurrent monoclonal B cells. JAK2‑mutated MPN patients have a significantly higher prevalence of clonal T‑LGL (17.2%) compared with BCR::ABL[+] MPN (3.3%) with diverse immunophenotypes, predominantly CD8[+] with frequent CD57 expression and CD5/CD7 aberrancy. A small subset of JAK2[+] T-LGL patients (2/28, 7.1%) had concurrent monoclonal B cells, no plasma cell clones were identified. Routine TRBC1‑based flow cytometric screening for T‑cell clonality is recommended in JAK2‑mutated MPN patients.

Core binding factor acute myeloid leukemia (CBF-AML)-defined by t(8;21) or inv(16) chromosomal rearrangements-is classified as favorable-risk disease per the European LeukemiaNet 2022 risk model and is typically treated with intensive chemotherapy. Patients unsuitable for intensive therapy increasingly receive hypomethylating agents plus venetoclax (HMA/ven), though CBF-AML was excluded from pivotal trials of this regimen. Furthermore, HMA/ven is typically administered as indefinite therapy in AML; however, there is increasing interest in exploring the feasibility of therapy cessation given persistent treatment-free remissions with this regimen. Here, we report the first case of sustained treatment-free remission following HMA/ven in CBF-AML. Features in this case that suggest a higher likelihood of achieving a durable treatment-free remission include inv(16) disease and rapid measurable residual disease (MRD) clearance. We summarize the current retrospective data comparing response rates of inv(16) vs. t(8;21) AML to HMA/ven: inv(16) AML consistently exhibits higher response rates compared with t(8;21) disease, although an overall survival benefit is not well established. Emerging data also suggest achieving MRD-negative complete remission after induction may predict more durable outcomes. This case provides proof-of-concept that carefully selected CBF-AML patients achieving sustained MRD-negative remission with HMA/ven can successfully discontinue therapy. Prospective evaluation of HMA/ven in unfit CBF-AML patients, weighed against dose-attenuated intensive chemotherapy, is needed to define its role and optimal duration.

The management of patients with essential thrombocythemia (ET) and extreme thrombocytosis (ExT) remains plagued by several unresolved issues. Therefore, we conducted a web-based survey to better understand hematologists' clinical approaches to ExT and to compare them with responses generated by artificial intelligence (AI) programs. A total of 56 hematologists participated. Cytoreductive treatment was preferred by 41.1% of respondents at a platelet threshold of ≥ 1000 × 10[9]/L and by 83.9% at ≥ 1500 × 10[9]/L. Assessment of vWF: RCo at diagnosis was reported by 78.6% of hematologists. In the presence of cardiovascular risk factors and the absence of acquired von Willebrand disease (vWD), aspirin therapy was favored by 91.1% and 78.6% of respondents for platelet counts ≥ 1000 × 10[9]/L and ≥ 1500 × 10[9]/L, respectively. Prevention of thrombosis, prevention of bleeding, and symptom control were cited with similar frequencies as reasons for initiating cytoreductive treatment. Artificial intelligence (AI)-generated recommendations supported vWF testing, favored cytoreductive treatment, particularly at platelet counts ≥ 1500 × 10[9]/L, and generally recommended aspirin only for patients with platelet counts ≥ 1000 × 10[9]/L in the absence of acquired vWD. Overall, ExT appeared to be an important driver of treatment decisions, particularly at platelet counts ≥ 1500 × 10[9]/L. Comparisons with AI-generated recommendations revealed few differences in treatment approaches across some clinical scenarios, supporting the exploratory nature of the AI analysis.

Histiocytic sarcoma is a rare and aggressive malignancy with poor outcomes under conventional chemotherapy. Activating MAPK pathway alterations, including BRAF V600E mutations, provide a rationale for targeted therapy; however, the durability of responses and the role of post-transplant maintenance remain unclear. We report a patient with refractory BRAF V600E-mutant histiocytic sarcoma who achieved complete remission following BRAF/MEK inhibition and subsequently underwent allogeneic stem cell transplantation. Post-transplant maintenance therapy with dabrafenib and trametinib was initiated early after engraftment. The patient achieved sustained complete remission with no radiological or molecular evidence of disease during follow-up exceeding one year. Circulating tumor DNA analysis remained negative for previously detected mutations. This case suggests that an integrated strategy combining targeted therapy, allogeneic transplantation, and post-transplant maintenance may enable durable disease control in high-risk BRAF-mutant histiocytic sarcoma and warrants further evaluation.

Glofitamab, a CD20×CD3 bispecific antibody, has shown durable activity in relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL), but real-world data from Korean patients and after CAR-T failure remain limited. We retrospectively analyzed 46 patients with RR-DLBCL treated with glofitamab monotherapy. Response and safety were assessed in all patients, whereas the main survival and prognostic analyses were conducted in the non-bridge-intent cohort (n = 41), excluding five bridge-intent patients. Median age was 57.5 years; patients had received a median of three prior lines, and 58.7% had failed prior CAR-T. In the overall cohort, the objective response rate was 39.1% and the complete response rate was 32.6%. In the non-bridge-intent cohort, median progression-free survival (PFS) and overall survival (OS) were 2.6 and 5.9 months, respectively, after a median follow-up of 8.2 months. Median duration of response was not reached, and 10 of 15 responders remained in response. Prior CAR-T exposure was not associated with PFS or OS. A longer pre-glofitamab interval was associated with improved PFS (adjusted hazard ratio 0.51 per category increase; p = 0.018), but not OS. Patients with an interval < 1 month had an ORR of 15.4% and median PFS of 1.0 month. Cytokine release syndrome occurred in 26.1%, all Grade 1 or 2; no immune effector cell-associated neurotoxicity syndrome or treatment-related deaths occurred. Glofitamab monotherapy demonstrated clinically meaningful activity and manageable safety in heavily pretreated RR-DLBCL. In exploratory analyses, a shorter pre-glofitamab treatment interval was associated with poorer outcomes; this hypothesis-generating observation requires prospective validation.

Treatment-free remission (TFR) is an established therapeutic goal for patients with chronic myeloid leukemia (CML) achieving sustained deep molecular response (DMR) on tyrosine kinase inhibitors (TKIs). However, evidence on TFR following bosutinib discontinuation remains limited. BOSUTFR is a multicenter, retrospective study by the Spanish CML Group (GELMC) evaluating TFR feasibility after bosutinib cessation in patients with chronic-phase CML. Twenty-five adults from 15 centers who maintained ≥MR4.0 for at least 2 years or discontinued for intolerance were included. The primary endpoint was TFR rate at 12 months. Thirteen patients (52%) stopped treatment after sustained MR4.0 and 12 (48%) due to intolerance, including 2 patients from fifth-line therapy. After a median follow-up of 4.6 years, 17/25 (68.0%) maintained TFR, with TFR rates at 12 and 24 months of 70.4% and 64.5%. No disease progressions or deaths occurred. All patients with molecular recurrence regained DMR after restarting bosutinib (n = 6) or switching to asciminib (n = 2). Median duration of bosutinib therapy before discontinuation was 4.5 years, and median DMR duration was 36 months. Notably, 9 of 11 patients (81.8%) who discontinued due to intolerance remained in TFR, including 4 of 5 who stopped in MMR. This is the largest real-world cohort of bosutinib discontinuations to date. Results confirm that bosutinib discontinuation is feasible and safe in real-world practice, including for patients who discontinue for intolerance, heavily pretreated patients, and patients with less stringent molecular response criteria.

Iron overload is a significant complication for patients with sickle cell disease (SCD) on chronic red blood cell (RBC) transfusion therapy. While pharmacological iron chelation therapy (ICT) is the standard of care, it is often associated with high costs, significant side effects, and poor adherence. Non-pharmacological interventions are increasingly explored as adjuncts to improve clinical outcomes, yet a comprehensive synthesis of this evidence is lacking. We conducted a scoping review and evidence gap mapping following the PRISMA-ScR guidelines. We systematically searched PubMed, Embase, and Cochrane Library from inception to May 2026 for studies evaluating non-pharmacological interventions in chronically transfused SCD patients with iron overload. Extracted data were synthesized into an evidence gap map to visualize the distribution of studies across intervention types and clinical outcomes. The search identified 14 eligible studies encompassing 642 participants. Interventions were categorized into dietary modifications (n = 5), nutritional supplementation (n = 4), physical activity (n = 3), and psychological/behavioral support (n = 2). The evidence gap map revealed a concentration of studies on short-term adherence and quality of life, with a notable paucity of long-term data on objective iron parameters (e.g., liver iron concentration) and organ-specific morbidity. The quality of evidence was generally low to moderate, limited by small sample sizes, lack of control groups, and heterogeneity in outcome measures. Non-pharmacological interventions show potential as adjuncts to iron chelation in chronically transfused SCD. However, significant evidence gaps remain, particularly regarding long-term objective outcomes. Future research should prioritize robust, longitudinal trials to establish standardized, evidence-based non-pharmacological protocols that can be integrated into comprehensive SCD care.

Cyanosis is an uncommon clinical presentation in infants, children and adolescents, but can manifest from conditions that range from benign to life-threatening. It is often a sign of serious cardiopulmonary disease that affects blood oxygenation levels, and will often present with additional symptoms of dyspnea, jaundice, or splenomegaly. Rare etiologies of cyanosis, including inherited red blood cell disorders, should also be considered. Herein, we report a case of a 17-year-old Japanese male with longstanding cyanosis, progressive anemia, and exercise intolerance with normal cardiopulmonary assessments. Methylene blue provided for the treatment of cyanosis but was ineffective. Laboratory evaluation demonstrated anemia (Hb 10-11 g/dL), macrocytosis (MCV 106 fL), reticulocytosis (9%), and platelets 160-179 × 10[9]/L. Hemoglobin electrophoresis workup showed an abnormal hemoglobin M fraction (~ 10%), and molecular testing confirmed HBB: c.277 C > T (p.His93Tyr), confirming Hemoglobin M-Hyde Park (Akita) disease. After being lost to follow-up and requiring transfusions, he later presented with marked splenomegaly and Hb 7.5 g/dL. A bone marrow biopsy was done which revealed significant erythroid dysplasia, not previously described in this entity. Administration of hydroxyurea reduced transfusion needs, increased fetal hemoglobin to 11%, and stabilized Hb at ~ 9 g/dL. In summary, Hb M-Hyde Park can present with cyanosis and dysplasia. Early genetic studies may prevent misdiagnosis of this rare hemoglobinopathy, for which hydroxyurea is a possible treatment option.

Hereditary high molecular weight kininogen (HMWK) deficiency is a rare autosomal recessive disorder characterized by a markedly prolonged activated partial thromboplastin time (APTT) without an associated bleeding diathesis. We report a patient presenting with significant APTT prolongation and profoundly reduced HMWK activity. Genetic analysis identified a novel homozygous deletion, c.628_629delAA, in exon 5 of the KNG1 gene, resulting in a p.Asn210Phe fs*15 frameshift mutation. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this mutation was classified as pathogenic. This mutation introduces a premature termination codon (PTC), leading to protein truncation. Family members carrying the heterozygous mutation exhibited mildly decreased HMWK activity but maintained normal APTT values. This case not only expands the mutational spectrum of the KNG1 gene but also deepens the understanding of the genetic characteristics of HMWK deficiency but also underscores the clinical importance of performing systematic genetic screening in both patients and their family members.

Hypogammaglobulinemia is increasingly recognized in B-cell malignancies, but whether its clinical significance differs by timing, present at diagnosis versus developing after treatment, remains unclear in diffuse large B-cell lymphoma (DLBCL). We retrospectively evaluated 181 adults with newly diagnosed DLBCL treated with rituximab-based immunochemotherapy at a tertiary referral center. Hypogammaglobulinemia was defined as serum IgG < 7 g/L and classified as baseline hypogammaglobulinemia (BHG), treatment-emergent hypogammaglobulinemia (TEHG), or absent. Among the study population, 107 patients (59.1%) developed hypogammaglobulinemia, including 30 (16.6%) with BHG and 77 (42.5%) with TEHG. Patients with BHG exhibited a more adverse baseline clinical profile characterized by poorer performance status and higher-risk disease features. Complete response rates differed significantly across groups and were lowest in patients with BHG (73.3%) compared with TEHG (88.3%) and no hypogammaglobulinemia (94.6%) (p = 0.008). BHG was also associated with the poorest survival outcomes, with median progression-free survival (PFS) and overall survival (OS) of 26.4 and 30.9 months, respectively. In multivariable analyses, BHG independently predicted infectious complications but was not an independent predictor of PFS. TEHG was associated with shorter PFS in the primary multivariable model; however, this association was not confirmed in a prespecified 6-month landmark analysis. These findings suggest that BHG and TEHG represent distinct clinical states in DLBCL. While BHG identifies a clinically vulnerable subgroup with increased infection risk and inferior outcomes, the prognostic significance of TEHG should be interpreted cautiously because of non-protocolized monitoring and potential ascertainment bias.

B-cell acute lymphoblastic leukemia (B-ALL) harboring the SET-NUP214 fusion constitutes an exceedingly rare and aggressive subtype. While this genetic aberration is a well-recognized hallmark of T-cell acute lymphoblastic leukemia (T-ALL), its clinical implications and therapeutic landscape in the B-cell lineage remain largely elusive. Herein, we report the first documented case of relapsed/refractory SET-NUP214-positive B-ALL achieving a successful response to a salvage regimen combining venetoclax with Hyper-CVAD chemotherapy.A 25-year-old male presented with profound cytopenias and 95.5% bone marrow blasts. Flow cytometric analysis characterized the malignant population as pro-B-ALL, with immunophenotypic expression of CD34, CD38, HLA-DR, CD7, and CD58, alongside partial CD19 and cCD79a, and myeloid co-expression (CD13/CD33). Molecular profiling identified the SET-NUP214 fusion transcript, accompanied by concurrent JAK3, PHF6, and PTPN11 mutations. The patient experienced a short-term relapse following induction remission with the VDLP regimen, and subsequent re-induction with the VDEP regimen failed. Subsequently, MRD-negative remission was achieved after adding venetoclax during the mid-course of Hyper-CVAD-A chemotherapy. This deep response facilitated a successful bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the patient maintaining sustained remission for 24 months post-transplant. Our findings suggest that venetoclax-based combinations may provide a potent reinduction strategy for refractory SET-NUP214-positive ALL, underscoring BCL-2 inhibition as a pivotal therapeutic intervention for this high-risk genomic subset.