bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–02–01
25 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Macrocytosis as an Early Pharmacodynamic Marker of Imatinib Efficacy in Chronic Myeloid Leukemia.
  2. Distinct trajectory of measurable residual disease in t(11;14) myeloma treated with quadruplet therapy.
  3. A myeloma identity crisis yields daratumumab resistance.
  4. Rapid molecular response kinetics to anti-PD1 based first-line treatment of Hodgkin lymphoma in the GHSG NIVAHL trial.
  5. Targeting proteostasis addiction in AML.
  6. Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study.
  7. Bruton tyrosine kinase inhibitors in combination with chemoimmunotherapy is an effective treatment for patients with Richter's syndrome.
  8. Ropeginterferon alfa-2b has minimal transplacental passage and breastmilk secretion in pregnant MPN patients.
  9. An Indirect Comparison of Zanubrutinib vs Acalabrutinib Plus Venetoclax in Patients With Treatment-Naive CLL.
  10. The proteasome: a gatekeeper stabilizing BCMA expression.
  11. Past, Present, and Future of Dexamethasone in Multiple Myeloma and AL Amyloidosis.
  12. Survival improvement in primary plasma cell leukemia: a retrospective analysis of novel agent-based regimens and stem cell transplantation.
  13. Treatment and Survival Outcomes in Follicular Lymphoma Patients with POD24: A Systematic Review and Meta-Analysis.
  14. Zalcitabine induces ferroptosis in multiple myeloma through the TFAM-cGAS-STING-SLC7A11 axis.
  15. Polycythemia vera and stiff-person syndrome: a case report.
  16. Undetectable Minimal Residual Disease in Multiple Myeloma: Bridging the Gap Between Clinical Trials and Real-life Application.
  17. Novel agents and therapeutic advances in T cell lymphoma.
  18. Blinatumomab in de novo AYA ALL-Results of the Australasian Leukaemia and Lymphoma Group ALL09 "SUBLIME" study.
  19. Ferric Pyrophosphate in Iron Deficiency Anemia Management: An Updated Review of Current Practices, Bioavailability Enhancement Techniques, and Future Directions.
  20. Immune biomarkers of increased infection risk in multiple myeloma.
  21. A Retrospective, Real-World Study of IV Iron Use to Treat Iron deficiency Anemia During Acute Infection.
  22. Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.
  23. American Society of Hematology (ASH) 2026 Guidelines on Diagnosis of Light Chain Amyloidosis.
  24. Universal Use of Novel Oral Anticoagulant Prophylaxis in Myeloma Patients Undergoing IMiD-Based Therapy: Real-World Experience.
  25. Zanubrutinib, lenalidomide, rituximab, temozolomide ± methotrexate as first-line treatment for primary central nervous system lymphoma: A prospective, open-label, multicentre clinical trial.
  1. J Clin Med. 2026 Jan 22. pii: 908. [Epub ahead of print]15(2):
    Macrocytosis as an Early Pharmacodynamic Marker of Imatinib Efficacy in Chronic Myeloid Leukemia.
    Fatih Yaman, Ibrahim Ethem Pinar, Sevgi Isik, Filiz Yavasoglu, Eren Gunduz, Hava Uskudar Teke, Neslihan Andic.
      Background: Macrocytosis commonly develops during imatinib therapy, but its relationship with cytogenetic and molecular outcomes in chronic myeloid leukemia (CML) remains unclear. We investigated whether increases in mean corpuscular volume (MCV) during imatinib treatment are associated with response depth and treatment persistence. Methods: In this retrospective study, we analyzed 101 adults with chronic-phase CML treated with a stable imatinib dose of 400 mg/day for at least 12 months. Patients with conditions that could confound MCV (hydroxyurea exposure, megaloblastic anemia, hypothyroidism, chronic liver disease, alcoholism) were excluded. Complete cytogenetic response (CCyR) and major molecular response (MMR) were assessed by conventional karyotyping and the BCR-ABL1 International Scale, respectively. Increased MCV was defined as MCV > 100 fL after six months of therapy, persisting thereafter. Associations between MCV dynamics, response, and switching to second-generation tyrosine kinase inhibitors were evaluated. Results: Twenty patients (20%) developed increased MCV. Overall, 86 patients (85%) achieved CCyR and 70 (69%) achieved MMR. All patients with increased MCV attained CCyR, compared with 66 of 81 (81%) without MCV elevation (p = 0.037), while MMR rates were 90% versus 64% (p = 0.030). During a median follow-up of 69 months, treatment modification was required in 1 of 20 (5%) patients with increased MCV versus 25 of 81 (31%) in the non-increased group (p = 0.018). Conclusions: MCV elevation during imatinib therapy is associated with deeper molecular response and reduced need for treatment modification. MCV dynamics may serve as an inexpensive pharmacodynamic marker to support risk assessment and guide monitoring in chronic-phase CML.
    Keywords:  chronic myeloid leukemia; cytogenetic response; imatinib; macrocytosis; mean corpuscular volume; molecular response; treatment outcomes
    DOI:  https://doi.org/10.3390/jcm15020908
  2. Blood. 2026 Jan 27. pii: blood.2025031952. [Epub ahead of print]
    Distinct trajectory of measurable residual disease in t(11;14) myeloma treated with quadruplet therapy.
    Susan Bal, Gayathri Ravi, Binod Dhakal, Natalie S Callander, Eva Medvedova, Bhagirathbhai Dholaria, Smith Giri, Kelly Godby, Rebecca Silbermann, Fady M Mikhail, Forest Huls, Vishnu Reddy, Luciano J Costa.
      Quadruplet (QUAD) induction and autologous stem cell transplantation (ASCT) leads to high rates of measurable residual disease (MRD)-negativity with improved outcomes in multiple myeloma (MM). The t(11;14) confers unique biology and different kinetics of treatment response. We analyzed MRD trajectories of patients treated with QUAD/ ASCT and MRD-adapted post ASCT management. Of the 302 patients assessed, 47 (16%) had t(11;14)+. Median follow up was 45.8 months. MRD negativity (10-5) for t(11;14)+ vs. t(11;14)- was 9% vs. 31% (P<0.001), 36% vs. 59% (P=0.004), and 53% vs. 75% (P=0.004) at post-induction, post-ASCT and any time on treatment, respectively. The rates of sustained MRD negativity (S-MRD)<10-5 were 38% vs. 46% (P=0.43). Median time to MRD<10-5 was 13.6 vs 7.7 months (P=0.002) for t(11;14)+ vs. t(11;14)-, respectively. PFS was superior for t(11;14)+ patients (P=0.012), with 4-year PFS rates of 90% vs. 72%. In multivariable analysis, S-MRD<10-5 (HR 0.41, P=0.002) and t(11;14)+ (HR 0.36, P=0. 048) were associated with reduced risk of progression or death, with no progression seen in t(11;14)+ patients who achieved S-MRD<10-5. In the setting of QUAD/ASCT therapy and MRD-adapted post ASCT management, t(11;14)+ NDMM in associated with improved prognosis despite slow conversion to MRD negativity.
    DOI:  https://doi.org/10.1182/blood.2025031952
  3. Blood. 2026 Jan 29. 147(5): 473-474
    A myeloma identity crisis yields daratumumab resistance.
    Abhishek Pandey, Benjamin Diamond.
      
    DOI:  https://doi.org/10.1182/blood.2025031281
  4. Blood Adv. 2026 Jan 27. pii: bloodadvances.2025018719. [Epub ahead of print]
    Rapid molecular response kinetics to anti-PD1 based first-line treatment of Hodgkin lymphoma in the GHSG NIVAHL trial.
    Jan-Michel Heger, Julia Mattlener, Peter Herhaus, Julia Meissner, Karolin Trautmann-Grill, Conrad-Amadeus Voltin, Jessica Schneider, Julia K Schleifenbaum, Sophie Julia Heidenreich, Carsten Kobe, Helen Kaul, Wolfram Klapper, Bastian von Tresckow, Peter Borchmann, Paul J Bröckelmann, Sven Borchmann.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2025018719
  5. Blood. 2026 Jan 29. 147(5): 479-480
    Targeting proteostasis addiction in AML.
    Mary L Clarke.
      
    DOI:  https://doi.org/10.1182/blood.2025031546
  6. Blood Adv. 2026 Jan 28. pii: bloodadvances.2025017519. [Epub ahead of print]
    Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study.
    Jason Gotlib, Andreas Reiter, Deepti H Radia, Iván Álvarez-Twose, Michael W Deininger, Tracy I George, Jens P Panse, Andrzej Mital, Kristen M Pettit, Alessandro M Vannucchi, Uwe Platzbecker, Olivier Hermine, Amro Elshoury, Cristina Livideanu, Ruben A Mesa, Celalettin Ustun, Massimo Triggiani, Ingunn Dybedal, Joseph G Jurcic, Roberta Zanotti, Stephen T Oh, Abdulraheem Yacoub, Elizabeth O Hexner, Prithviraj Bose, Stephanie G Lee, Wolfgang R Sperr, Elizabeth A Griffiths, Matthew Butler, Johannes Lübke, Ilda Bidollari, Hui-Min Lin, Svetlana N Rylova, Saša Dimitrijević, Javier I Muñoz-González, Daniel J DeAngelo.
      Advanced systemic mastocytosis (AdvSM), a clonal hematologic neoplasm driven predominantly by D816V-mutant KIT, is often characterized by organ damage. Associated hematologic neoplasms (AHN; usually myeloid) are often present, leading to poor survival. We report on the oral, highly selective, potent KIT D816V inhibitor avapritinib (200-mg once-daily starting dose) with >4 years follow-up from the fully enrolled PATHFINDER (NCT03580655) study. Endpoints included overall response rate (ORR; primary), duration of response (DOR), progression-free survival (PFS), overall survival (OS), changes in objective biomarkers of disease, and safety (all secondary). Of 107 patients with AdvSM (including 71 [66%] with SM-AHN; overall population median follow-up: 49 months), 83 were response evaluable. ORR was 73% (95% confidence interval [95% CI], 63%-83%). Median DOR was 58 months, PFS 51 months, and OS 62 months. Disease progression occurred in 21/107 patients, predominantly in SM-AHN and largely driven by the AHN. Reductions in objective biomarkers of disease were observed. Most frequent (≥30% patients) treatment-emergent adverse events (TEAEs) (any grade; grade ≥3) were thrombocytopenia (58%; 31%); periorbital edema (57%; 6%), anemia (54%; 33%), peripheral edema (48%; 2%), and diarrhea (36%; 5%). Adverse events of special interest were cognitive effects (34%; 8%) and intracranial bleeds (4%, 2%). Eleven (10%) patients experienced TEAEs leading to death, of which 1 was deemed related to avapritinib by the principal investigator. With 4-year follow-up, avapritinib-treated patients with AdvSM experienced deep and durable responses and a favorable benefit-risk profile.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017519
  7. Leuk Res Rep. 2026 ;25 100564
    Bruton tyrosine kinase inhibitors in combination with chemoimmunotherapy is an effective treatment for patients with Richter's syndrome.
    Tristan Meier, Giovann Huynh, Ernesto Ayala, Han W Tun, Madiha Iqbal.
      Richter's syndrome (RS) is characterized by transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into an aggressive lymphoma. While significant treatment advances have been made in the management of CLL/SLL, current front-line management of RS is consistent with chemoimmunotherapy (CIT), a therapeutic approach adopted from the management of de-novo diffuse large B-cell lymphoma (DLBCL). In de-novo DLBCL, CIT alone can potentially cure a significant percentage of patients; however in RS, outcomes with CIT alone are particularly poor. Therefore there is a significant unmet need to improve the current standard of care for the management of RS. We present a case of a patient with newly diagnosed RS who was treated with a novel upfront combination of CIT and a Bruton tyrosine kinase inhibitor, resulting in excellent long-term outcomes. We also present accompanying literature review highlighting other anecdotal cases reported with similar therapeutic approach and discuss emerging treatment strategies in the management of RS.
    Keywords:  Bruton tyrosine kinase inhibitors; Chronic lymphocytic leukemia; Richters syndrome
    DOI:  https://doi.org/10.1016/j.lrr.2026.100564
  8. Blood Adv. 2026 Jan 26. pii: bloodadvances.2025018811. [Epub ahead of print]
    Ropeginterferon alfa-2b has minimal transplacental passage and breastmilk secretion in pregnant MPN patients.
    Tsewang Tashi, Lee-Yung Shih, Yi-Te Yo, Amy Sullivan, Ho-Yen Chueh, Ming-Chung Kuo, Amanda Smith, Soo Jin Kim, Brynn Parsegov, Brandi N Reeves, Jihyun Song, Josef T Prchal.
      Pregnancy in patients with myeloproliferative neoplasms (MPNs) poses unique challenges due to increased risks of maternal complications and adverse fetal outcomes. Interferon-alpha (IFN-α) has been shown to be safe and is the preferred cytoreductive agent in pregnant MPN patients. Ropeginterferon alfa-2b (RopegIFN) is a novel monopegylated interferon and is the only IFN approved for the treatment of polycythemia vera (PV), but also used for essential thrombocythemia (ET) and myelofibrosis; yet, limited data exist on the safety of RopegIFN during pregnancy and lactation. In this study, we report four cases of pregnant MPN patients treated with RopegIFN, in whom maternal blood, umbilical cord blood, and breast milk samples were analyzed to assess exposure to RopegIFN. Quantitative ELISA and dot-blot assays demonstrated therapeutic levels of RopegIFN in maternal plasma but negligible levels in cord blood and breast milk, suggesting minimal transplacental transfer and excretion into breast milk. This is the first study to provide pharmacokinetic evidence of RopegIFN exposure during pregnancy and lactation. These findings support the safety of RopegIFN use in pregnant ET and PV patients and highlight the need for a collaborative registry to collect real-world data and guide management for this high-risk population.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018811
  9. Blood Adv. 2026 Jan 26. pii: bloodadvances.2025018536. [Epub ahead of print]
    An Indirect Comparison of Zanubrutinib vs Acalabrutinib Plus Venetoclax in Patients With Treatment-Naive CLL.
    Mazyar Shadman, Constantine S Tam, Danielle M Brander, Marcus Lefebure, Keri Yang, Sheng Xu, Tian Tian, Nataliya Kuptsova-Clarkson, Rhys Williams, Jamie Hirata, Talha Munir.
      In the phase 3 randomized SEQUOIA study (NCT03336333), zanubrutinib (arm A) demonstrated superior progression-free survival (PFS) compared with bendamustine-rituximab (BR; arm B) in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without del(17p). In the phase 3 AMPLIFY study (NCT03836261), acalabrutinib-venetoclax with or without obinutuzumab demonstrated prolonged PFS vs chemoimmunotherapy (investigator's choice of fludarabine, cyclophosphamide, and rituximab [FCR] or BR) in patients with treatment-naive CLL without del(17p) or TP53 mutations. Compared with AMPLIFY, the patient population in SEQUOIA was unsuitable for FCR and included patients with TP53 mutations. The aim of this post hoc analysis was to investigate the efficacy of zanubrutinib in patients from SEQUOIA vs a clinically similar patient population treated with acalabrutinib-venetoclax in AMPLIFY. A numerically greater 3-year investigator-assessed PFS (PFS-INV) was observed with zanubrutinib (84.3%) in the SEQUOIA population acalabrutinib-venetoclax in AMPLIFY (78.9%). When matching SEQUOIA to the AMPLIFY population by FCR eligibility, a greater PFS benefit with zanubrutinib was reported (89.2% vs 78.9%, respectively). To support the comparison of zanubrutinib vs acalabrutinib-venetoclax, an anchored matching-adjusted indirect comparison was performed, which showed that zanubrutinib was associated with prolonged PFS-INV vs acalabrutinib-venetoclax when adjusted for various baseline characteristics. Zanubrutinib also demonstrated longer PFS whether adjusted for age (PFS-INV hazard ratio [HR], 0.26; 95% CI, 0.13-0.54; P<.0003) or unadjusted (PFS-INV HR, 0.45; 95% CI, 0.23-0.88; P=.0197). These results highlight zanubrutinib monotherapy as an effective treatment option for all patients with treatment-naive CLL/SLL, including patients who might otherwise be considered for more intensive fixed-duration combination regimens.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018536
  10. Blood. 2026 Jan 29. 147(5): 478-479
    The proteasome: a gatekeeper stabilizing BCMA expression.
    Aina Oliver-Caldés, Carlos Fernández de Larrea.
      
    DOI:  https://doi.org/10.1182/blood.2025030422
  11. J Clin Oncol. 2026 Jan 27. JCO2501713
    Past, Present, and Future of Dexamethasone in Multiple Myeloma and AL Amyloidosis.
    Rahul Banerjee, Tracy King, Beth Faiman, Susie Harding, Aaron S Rosenberg, Vaishali Sanchorawala, Joseph R Mikhael, Andrew J Cowan.
      For over half a century, dexamethasone has been a backbone of treatment regimens for plasma cell disorders such as multiple myeloma (MM) and light-chain (AL) amyloidosis. Dexamethasone doses of approximately 40 milligrams (mg) once weekly are often continued for months or years despite accumulating evidence that they can cause dose-dependent toxicities such as cataracts and infections. Acute dexamethasone-related toxicities such as insomnia or pedal edema, even if low-grade by clinical criteria, can significantly interfere with patient quality of life. In the past 5 years, several trials have demonstrated the efficacy and improved tolerability of corticosteroid-sparing regimens in MM. In this review, we discuss these and other studies to comprehensively assess the role of dexamethasone in the modern era. In newly diagnosed MM, robust data support planned dexamethasone discontinuation after one to two cycles in older and frailer patients. In the maintenance setting, the risk-benefit ratio of prolonged dexamethasone is unfavorable. While randomized trials have shown that once-weekly dexamethasone adds value within doublet regimens in relapsed/refractory MM, its contribution to triplet and quadruplet regimens is uncertain. Furthermore, data suggest that indefinite dexamethasone may actually limit the feasibility and efficacy of subsequent postprogression therapies. In AL amyloidosis, dexamethasone 40 mg once weekly for 6 months is excessive and may predispose patients to volume overload. In our review, we also discuss dexamethasone as a premedication for CD38-targeted monoclonal antibodies (where it is no longer required after one to two cycles) and for supportive care (where lower doses of 4-8 mg as needed can often suffice). Despite the historical inertia of corticosteroid-containing regimens in clinical trials and practice guidelines, corticosteroid-sparing regimens warrant prospective investigation across the gamut of plasma cell disorders.
    DOI:  https://doi.org/10.1200/JCO-25-01713
  12. Front Oncol. 2025 ;15 1727117
    Survival improvement in primary plasma cell leukemia: a retrospective analysis of novel agent-based regimens and stem cell transplantation.
    Yong Xu, Jie He, Lanxin Chen, Jinwen Liu, Min Zhou, Bing Chen, Hua Bai.
       Background: This study aimed to characterize the clinical profile and treatment outcomes of primary plasma cell leukemia (pPCL) patients, defined by ≥5% circulating plasma cells (CPCs) on peripheral blood smear, who received novel agent-based induction therapy.
    Methods: A retrospective analysis of 46 pPCL patients treated at Nanjing Drum Tower Hospital from March 2014 to April 2025 was conducted. Their clinical and laboratory manifestations, prognostic factors, and efficacy of induction therapies were focused upon.
    Results: Advanced-stage disease predominated in our cohort. The most frequent cytogenetic abnormalities were chromosome 1q21+ and del(13q14). Failure to achieve ≥very good partial response (VGPR) after first-line therapy independently predicted inferior overall survival (OS) (HR = 0.095, 95%CI 0.022-0.421, p = 0.002) and shorter median time to next therapy (TTNT) (HR = 0.088, 95%CI 0.024-0.329, p<0.001). Intensified regimens combining proteasome inhibitors (PIs)/immunomodulatory drugs (IMiDs) with venetoclax (Ven) significantly improved ≥VGPR rates, particularly when followed by autologous stem cell transplantation (ASCT), prolonged median OS.
    Conclusion: Despite novel agents, pPCL maintains poor prognosis, with treatment failure strongly associated with suboptimal first-line response. Therapeutic intensification through PIs/IMiDs with Ven (guided by t(11;14)) and ASCT consolidation may enhance depth of remission and survival outcomes.
    Keywords:  autologous stem cell transplantation; primary plasma cell leukemia; prognostic factors; treatment response; venetoclax
    DOI:  https://doi.org/10.3389/fonc.2025.1727117
  13. Blood Adv. 2026 Jan 26. pii: bloodadvances.2025018474. [Epub ahead of print]
    Treatment and Survival Outcomes in Follicular Lymphoma Patients with POD24: A Systematic Review and Meta-Analysis.
    Jing Shen, Jingyi Zhang, Zhengyu Zhu, Haobo Ma, Junpeng Zhang, Fan Zhou, Hua Tian, JingHua Liu.
      Follicular lymphoma (FL) with progression within 24 months (POD24) is associated with poor prognosis and represents clinical challenges. Therefore, we performed a systematic review and pooled analysis of patients with POD24. Twenty-one trials involving 1242 participants were included, assessing the overall response rate (ORR), complete response (CR), duration of response (DOR), and progression-free survival (PFS). In some trials we compared pooled response rates between POD24 and non-POD24 populations with the same treatment regimen. Four trials have evaluated chimeric antigen receptor (CAR) T-cell therapy in patients with POD24. Upon pooled analysis, ORR was 91.2% (95% CI: 83.7-98.7%) with significant heterogeneity (P=0.0414, I²=68.61%), and CR was 75.7% (95% CI: 55.1-96.4%) with significant heterogeneity (P<0.0001, I²=93.99%). The specific response rates for different bispecific antibodies (BsAbs) in POD24 were pooled analysis, the ORR was 81.6% (95% CI: 75.9-87.3%) with no heterogeneity (P=0.6958, I²=0%), and CR was 65.7% (95% CI: 57.1-74.3%) with moderate heterogeneity (P=0.2148 I²=34.99%). Anti-CD19 antibody-drug conjugates (ADCs)/ monoclonal antibody (mAb): the ORR and CR of Loncastuximab+ rituximab and Tafasitamab+R2 (lenalidomide+rituximab) were 100%, 79.3% and 87.5%, 43.2%, respectively. phosphatidylinositol 3-kinase (PI3K) inhibitors and anti-CD20 mAb-containing regimens were also pooled analysis. Our results demonstrated that anti-CD19 CAR-T therapy achieved the highest complete response rate. Additionally, bispecific antibodies, anti-CD19 ADC/mAb, and the combination of lenalidomide with obinutuzumab or rituximab also exhibited excellent efficacy. Notably, lenalidomide plus obinutuzumab showed superior efficacy compared to R2.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018474
  14. J Transl Med. 2026 Jan 27.
    Zalcitabine induces ferroptosis in multiple myeloma through the TFAM-cGAS-STING-SLC7A11 axis.
    Juan Hui, Jiao Jia, Juan Feng, Hailong Tang, Li Xu, Wenrui Sun, Hongjuan Dong, Shan Gao, Chunyan Zhang, Biao Tian, Guangxun Gao.
      
    Keywords:  Ferroptosis; Mitophagy; Multiple myeloma; TFAM; Zalcitabine; cGAS-STING pathway
    DOI:  https://doi.org/10.1186/s12967-026-07749-3
  15. BMC Neurol. 2026 Jan 24.
    Polycythemia vera and stiff-person syndrome: a case report.
    Haixia Mu, Fengxia Ji, Rongfeng Du, Lingyan Hou, Yanni Li, Xiujun Yang, Chunxiao Shao, Kaijuan Hou, Yanping Wang.
       BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm, characterized by trilineage hypercellularity, which increases the risk of thrombosis. Stiff-person syndrome (SPS) is a very rare autoimmune neuronal excitability disorder, in which antibodies disrupt the balance between excitatory and inhibitory neurotransmitters, leading to stiffness and spasms of agonist and antagonist muscles.
    CASE PRESENTATION: This report describes the first known case of PV and SPS occurring simultaneously in a middle-aged male patient. He presented with back stiffness and painful abdominal spasms and was found to have erythrocytosis incidentally. He had high JAK2 V617F mutation burden and was positive for anti-GAD65 antibody. Progressively intensified therapy was given until his symptoms resolved.
    CONCLUSIONS: This case highlights the diagnostic and therapeutic challenges of these conditions as well as the need for further exploration of potential shared molecular mechanisms between PV and SPS.
    Keywords:  Autoimmune neurological diseases; Janus kinase 2; Myeloproliferative neoplasms; anti-GAD antibodies
    DOI:  https://doi.org/10.1186/s12883-025-04524-7
  16. Clin Lymphoma Myeloma Leuk. 2025 Dec 24. pii: S2152-2650(25)04322-8. [Epub ahead of print]
    Undetectable Minimal Residual Disease in Multiple Myeloma: Bridging the Gap Between Clinical Trials and Real-life Application.
    Roberto Mina, Elisabetta Antonioli, Gregorio Barilà, Niccolò Bolli, Cirino Botta, Anna Furlan, Carmine Liberatore, Marina Martello, Sonia Moré, Stefania Oliva, Bernardo Rossini, Elona Saraci, Antonio Giovanni Solimando, Paola Storti, Elena Zamagni.
      Much evidence supports the assessment of minimal residual disease (MRD) status in the clinical management of multiple myeloma (MM). Using highly sensitive next-generation flow cytometry and next-generation sequencing tests to detect MRD enables clinicians to evaluate the depth of response and therefore the prognosis of patients with MM as achieving deep and sustained (≥ 12 months) undetectable MRD correlates with prolonged survival in patients with MM. Because of this, undetectable MRD (also referred to as MRD-negativity) has been recognized and approved by the FDA as an early endpoint in clinical trials to accelerate regulatory approval of new treatments for MM. However, many questions remain around how (methods, sensitivity levels), who (all patients vs. those achieving complete/partial response), and when to test in relation to treatment phases, defining the optimal duration for sustained undetectable MRD, and how MRD can be used to guide treatment strategies in clinical practice. This narrative review has examined data from key clinical trials in MM to analyze the implementation of MRD testing in the newly-diagnosed and relapsed/refractory MM settings. We have also summarized trials that test MRD-driven approaches.
    Keywords:  Diffusion-weighted imaging; Next-generation flow; Next-generation sequencing; Positron-emission tomography/computed tomography; Whole-body MRI
    DOI:  https://doi.org/10.1016/j.clml.2025.12.016
  17. Int J Hematol. 2026 Jan 27.
    Novel agents and therapeutic advances in T cell lymphoma.
    Yuko Shirouchi, Dai Maruyama.
      Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of aggressive lymphomas with generally poor outcomes. CHOP or CHOP-like regimens have long been the standard frontline therapy; however, the addition of brentuximab vedotin has improved overall survival and established a new standard of care for CD30-positive PTCL. Despite this advance, the outcomes of relapsed or refractory (R/R) disease remain dismal. In recent years, multiple novel agents have been developed for the treatment of PTCL, particularly for R/R settings. Molecular profiling has refined disease classifications, identifying subtypes such as nodal T follicular helper (TFH) lymphoma, PTCL-GATA3, and PTCL-TBX21, which differ in their pathogenesis, prognosis, and potential therapeutic vulnerabilities. Epigenetic modulators, including histone deacetylase inhibitors and an EZH1/2 inhibitor, have demonstrated particularly high activity in TFH-derived subtypes, supporting the integration of biomarker-driven patient selection as a path toward precision medicine in PTCL. This review summarizes current insights into the genetic landscape, recent clinical advances in novel agents, and future perspectives on therapeutic stratification, highlighting the need to translate molecular insights into durable clinical benefits for patients with PTCL.
    Keywords:  ATL; Lymphoma; Novel agents; PTCL; T-cell lymphoma; Targeted therapy
    DOI:  https://doi.org/10.1007/s12185-026-04165-7
  18. Hemasphere. 2026 Jan;10(1): e70291
    Blinatumomab in de novo AYA ALL-Results of the Australasian Leukaemia and Lymphoma Group ALL09 "SUBLIME" study.
    Australasian Leukaemia and Lymphoma Group
      Pediatric regimens improve outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) patients. End-consolidation (time point 2 [TP2]) minimal residual disease negativity (MRDneg) is associated with improved survival. In this study, standard consolidation chemotherapy was replaced with blinatumomab to improve TP2 MRDneg-a key survival surrogate in B-lineage ALL. From 2019 to 2022, 55 patients constituted the intention-to-treat (ITT) cohort, median age 25 (range, 16-39) years. Using a Simon's 2-stage design, blinatumomab replaced standard consolidation chemotherapy cycles with TP2 MRDneg as the primary endpoint. Blinatumomab was associated with an improved TP2 MRDneg rate of 70.8% (95% CI, 55.9%-83.0%) versus the null hypothesis of 60% (P = 0.037). When compared to our previous ALL06 study, median time from protocol I commencement to next treatment phase was 84 versus 97 days (P = 0.0001), with 82.7% versus 45.1% (P < 0.0001), commencing protocol M or high-risk block therapy by day 94. Induction mortality was 1.8%. Blinatumomab was well tolerated. Median follow-up was 42.9 (range, 1.9-54.7) months, with 3-year disease-free survival (DFS) 88.6% (95% CI, 76.3%-94.7%) and 3-year overall survival (OS) 90.5% (95% CI, 78.6%-95.9%) in the ITT cohort. Higher than medium-risk patients had poorer DFS but not OS. Standard genomic risk patients had 100% 3-year DFS and OS. Adverse genomic risk stratified by TP2 MRDpos predicted poorer DFS but not OS. Blinatumomab consolidation for de novo B-lineage AYA ALL was associated with high MRDneg rates and excellent survival, particularly in standard-risk disease. Genomics may assist in predicting response to blinatumomab in de novo ALL (ACTRN12618001734257).
    DOI:  https://doi.org/10.1002/hem3.70291
  19. Curr Pharm Des. 2026 Jan 22.
    Ferric Pyrophosphate in Iron Deficiency Anemia Management: An Updated Review of Current Practices, Bioavailability Enhancement Techniques, and Future Directions.
    Bindu Soni, Riya Shivgotra, Kamal Kishore Kashyap, Hossamaldeen Bakrey, Jaanvi Khanna, Subheet Kumar Jain.
      According to the World Health Organization, Anemia is a health concern that impacts a substantial number of individuals globally, with 50% of cases due to iron deficiency and the remaining 50% being caused by other conditions and vitamin deficiencies. Iron deficiency anemia can cause several health issues, such as weakness, exhaustion, poor cognitive function, and a higher chance of pregnancy difficulties. Iron supplementation, particularly through dietary sources and supplement formulations, is fundamental in addressing this condition and is favored for managing mild to moderate cases. Ferrous and ferric iron are two types of iron that are often employed. Ferric pyrophosphate is a novel compound, complexed with pyrophosphate, is directly absorbed in the intestine, particularly by M cells in the duodenum. Ferric pyrophosphate is favored due to its higher elemental iron content, superior bioavailability, tolerability, and minimal impact on food color, taste, and texture. This review offers an in-depth investigation of ferric pyrophosphate as an alternative therapy for iron deficiency anemia because no review article currently available has compiled the research trends, benefits, and drawbacks of this drug. It summarizes pre-clinical and clinical studies on ferric pyrophosphate, exploring its pathogenesis, chemistry, safety, and efficacy.
    Keywords:  Ferric pyrophosphate; bioavailability; fortification.; hemoglobin; iron deficiency anemia; nanotechnology
    DOI:  https://doi.org/10.2174/0113816128392575251013123818
  20. Blood. 2026 Jan 29. pii: blood.2025031744. [Epub ahead of print]
    Immune biomarkers of increased infection risk in multiple myeloma.
    Aintzane Zabaleta, Luis-Esteban Tamariz-Amador, Ioannis V Kostopoulos, Romanos Sklavenitis Pistofidis, Febe Smits, Paula Rodriguez-Otero, Carmen Roncal, Michelle P Aranha, David Žihala, Michaela Machu, Nikolaos Tsakirakis, Panagiotis Bakouros, Ourania Tsitsilonis, Irene Solia, Cristina Moreno, Catarina Maia, Esperanza Martin-Sanchez, José Juan Pérez, Cristina Encinas, Rafael Ríos-Tamayo, Albert Oriol, María-Jesús Blanchard, Felipe de Arriba, Esther González-García, Sunil Lakhwani, Anna Sureda, Valentín Cabañas, Fernando Escalante, Estrella Carrillo-Cruz, Albert Pérez-Montaña, Enrique María M Ocio, Joan Bargay, Alberto Orfao, Tomas Jelínek, Irene M Ghobrial, Tuna Mutis, Sonja Zweegman, Evangelos Terpos, Efstathios Kastritis, Joaquín Martínez-López, Juan-Jose Lahuerta, Carlos Fernández de Larrea, Laura Rosiñol, Joan Bladé, Maria-Victoria Mateos, Jesús F San-Miguel, Maria Teresa Cedena, Noemi Puig, Bruno Paiva.
      Infection remains a leading cause of morbidity in multiple myeloma. Preventing infections is paramount and immune profiling could reflect the cumulative effect of host, tumor and treatment-related immunosuppression. However, current understanding of immune dysfunction and its association with infection is limited. To address this gap in knowledge and identify immune biomarkers of increased infection risk, we performed immune profiling using next-generation flow cytometry in bone marrow and peripheral blood samples from 1,786 patients at various disease stages and treatment scenarios. Patients developing infection had significantly lower percentages of CD27+ B cells and CD27- NK cells, as well as increased CD27-/CD27+ T-cell ratio in bone marrow. These immune risk factors were validated in three independent datasets. An immune score was developed to stratify patients with ≤1 vs ≥2 of the aforementioned risk factors, which was associated with higher infection incidence (35% vs 60%, P <.001). The immune score (odds ratio: 2.31, P <.001), disease stage and CD38, BCMA or GPRC5D targeted therapy were independently associated with infection incidence. All cell types detectable in bone marrow and peripheral blood were significantly correlated, suggesting that immune biomarkers of increased infection risk could be monitored using minimally-invasive methods that are available in routine laboratories.
    DOI:  https://doi.org/10.1182/blood.2025031744
  21. Blood. 2026 Jan 27. pii: blood.2025031965. [Epub ahead of print]
    A Retrospective, Real-World Study of IV Iron Use to Treat Iron deficiency Anemia During Acute Infection.
    Haris Sohail, Jennifer Elizabeth Collins, Kok Hoe Chan, Mohammad Ahsan Alamgir, Amir Shahzad Kamran.
      The administration of intravenous (IV) iron to treat anemia during acute infection remains controversial due to concerns of exacerbating the infection. We conducted a retrospective cohort study using the TriNetX Research Network (2000 to June 2025) to evaluate the safety and efficacy of IV iron administration in adults with iron-deficiency anemia and infection (methicillin-resistant Staphylococcus aureus [MRSA] bacteremia, pneumonia, urinary tract infection [UTI], colitis, or cellulitis). Patients must have received antibiotics within 2 days of infection for inclusion and were stratified by IV iron exposure. Propensity matching (1:1) was performed within each cohort. Survival was significantly higher (p<0.001 for each infection type) at both 14 and 90 days in patients who received IV iron (MRSA bacteremia 97.6% vs 95.0% and 88.6% vs 83.8%; pneumonia 95.7% vs 91.5% and 84.7% vs 78.1%; UTI 97.6% vs 95.7% and 89.1% vs 85.6%; colitis 97.6% vs 95.5% and 89.7% vs 83.8%; and cellulitis 98.5% vs 97.4% and 92.2% vs 89.2%). Hemoglobin recovery 60-90 days after infection was significantly greater (all p<0.001) when IV iron was administered across all subgroups (MRSA bacteremia +1.3 vs +1.0 g/dL; pneumonia +1.3 vs +1.0 g/dL; UTI (+1.4 vs +1.0 g/dL; colitis +1.5 vs +0.7 g/dL; and cellulitis +1.4 vs +0.9 g/dL). The findings observed for each infection type studied suggest that IV iron administration during acute infection does not exacerbate infection and is associated with improved survival and enhanced recovery from anemia in hospitalized patients. Prospective studies are needed to confirm these findings and expand their applicability.
    DOI:  https://doi.org/10.1182/blood.2025031965
  22. Blood Adv. 2026 Jan 29. pii: bloodadvances.2025018369. [Epub ahead of print]
    Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.
    Jeremy T Baeten, Sumedha Agashe, Imene Tabet, Jack T Wooldridge, Amber Carter, Jamie N Butler, Christopher A Miller, Nichole M Helton, Annabel Quinet, Kimberly B Johansson, Yichan Yang, Geoffrey L Uy, Alessandro Vindigni, Daniel C Link.
      TP53 mutations are found in 10-15% of myeloid neoplasms and are associated with a dismal prognosis. Although hypomethylating agents, such as decitabine, are active in TP53-mutated myeloid neoplasms (TP53-MN), mutation clearance is rarely complete and nearly all patients relapse. Molecular determinants of response to hypomethylating agents in TP53-MN are poorly understood. Here, we show that decitabine induces replicative stress with decreased replication fork progression, induction of single-strand DNA breaks, and activation of the ATR pathway. Resolution of decitabine-induced replication stress is impaired in TP53-mutated acute myeloid leukemia (AML) cells, representing a potential therapeutic vulnerability. Indeed, the combination of decitabine and ATR inhibition (ATRi) induces synthetic lethality that is selective for TP53-AML and due, in part, to induction of mitotic catastrophe. Interestingly, this synergistic lethality was not observed with azacitidine or treatment with GSK3685032, a potent DNMT1 inhibitor, both of which produce a comparable level of global hypomethylation to decitabine. Treatment with decitabine and ATR inhibitor reduces leukemia burden and prolongs survival in in vivo mouse models of TP53-mutated AML. Collectively, these show that TP53 loss generates a selective vulnerability to decitabine-induced replication stress, with the combination of ATR inhibition and decitabine showing promise as a new therapeutic approach for TP53-MN.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018369
  23. Blood Adv. 2026 Jan 27. pii: bloodadvances.2025017073. [Epub ahead of print]
    American Society of Hematology (ASH) 2026 Guidelines on Diagnosis of Light Chain Amyloidosis.
    Vishal Kukreti, Matthew D Seftel, Maria Adela Aguirre, Muayad Azzam, Deborah Boedicker, Naresh Bumma, Antonia S Carroll, Raymond Comenzo, Joselle Cook, Noel R Dasgupta, Alfredo De La Torre, Angela Dispenzieri, Faizi Jamal, Hassan Kawtharany, Jack Khouri, Nelson Leung, Jamil Nazzal, Maria M Picken, Shahzad Raza, Vaishali Sanchorawala, Nitasha Sarswat, Hira Shaikh, Daulath Singh, Reem A Mustafa.
      Light chain (AL) amyloidosis is a rare disease caused by the misfolding of immunoglobulin light chains produced by a plasma cell dyscrasia. Patients can present with involvement of many organs, including the heart, kidneys, liver, nerves and other sites, resulting in a high symptom burden. Timely and accurate diagnosis is important to prevent organ failure and improve patient survival. These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients and clinicians in the timely and effective diagnosis of AL amyloidosis. ASH formed a multidisciplinary guideline panel that included 22 individuals representing various medical specialties (academic/community hematology, nephrology, neurology, cardiology, internal medicine and pathology) as well as one patient representative. The group was balanced to minimize potential bias from conflicts of interest. Kansas University Medical Center supported the guideline development process, including updating or performing systematic evidence reviews (up to 6th of March 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. The panel agreed on 12 recommendations. The use of serum immunofixation, urine immunofixation and serum free light chains enhances the clinical suspicion of AL amyloidosis. The diagnosis of AL amyloidosis can be made effectively through surrogate biopsies which require both a bone marrow biopsy and fat pad sampling However, target organ biopsies maybe favoured in certain clinical situations.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017073
  24. J Clin Med. 2026 Jan 07. pii: 453. [Epub ahead of print]15(2):
    Universal Use of Novel Oral Anticoagulant Prophylaxis in Myeloma Patients Undergoing IMiD-Based Therapy: Real-World Experience.
    Yasa Gul Mutlu, Ebrar Uzunabdullah, Duha Yahya, Hasan Basri Ergün, Süreyya Yiğit Kaya, Senem Maral, Hüseyin Saffet Beköz, Leylagül Kaynar, Ömür Gökmen Sevindik.
      Background/Objectives: Multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs) are at increased risk of venous thromboembolism (VTE). Standard prophylaxis typically involves aspirin or low-molecular-weight heparin (LMWH), guided by risk assessment tools such as SAVED and IMPEDE-VTE. However, these models have practical limitations, and real-world evidence supporting novel oral anticoagulants (NOACs) as primary prophylaxis remains limited. Methods: In this retrospective, single-center study, we analyzed 101 MM patients treated with IMiD-based therapy between January 2020 and December 2024. All patients received NOAC prophylaxis (apixaban 2.5 mg twice daily or rivaroxaban 10-20 mg once daily), irrespective of baseline thrombotic risk. Clinical characteristics, comorbidities, and treatment details were collected. The primary outcome was objectively confirmed VTE, while secondary outcomes included bleeding events and treatment feasibility, assessed by treatment continuation without clinically significant bleeding. Results: Median age was 63 years (range 35-89); 36.6% were female. Lenalidomide and pomalidomide were used in 86.1% and 13.9%, respectively. Twenty-eight patients (27.7%) had relapsed/refractory disease, while 72.3% were newly diagnosed. Over a median NOAC exposure of 6 months, two patients (2.0%) developed VTE (both deep vein thrombosis). One major bleeding event (1.0%) occurred. Conclusions: Universal NOAC prophylaxis in MM patients receiving IMiD-based therapy was associated with a low incidence of thromboembolic events and an acceptable safety profile. These real-world findings suggest that NOACs may represent a practical and effective alternative to aspirin or LMWH, potentially overcoming the limitations of score-based prophylaxis strategies.
    Keywords:  multiple myeloma; novel oral anticoagulants; thromboprophylaxis
    DOI:  https://doi.org/10.3390/jcm15020453
  25. Br J Haematol. 2026 Jan 26.
    Zanubrutinib, lenalidomide, rituximab, temozolomide ± methotrexate as first-line treatment for primary central nervous system lymphoma: A prospective, open-label, multicentre clinical trial.
    Jia Song, Huijuan Jiang, Kai Ding, Hui Liu, Yihao Wang, Shan Gao, Yue Ren, Zhaoyun Liu, Jie Zhuo, Bing Li, Guokai Wang, Zongjiu Jiao, Da Gao, Rong Fu.
      In this prospective, multicentre clinical trial, we evaluated zanubrutinib combined with lenalidomide, temozolomide and rituximab monoclonal antibody ± methotrexate (RLZT ± MTX) as first-line treatment for primary central nervous system lymphoma. RLZT ± MTX demonstrated good efficacy and safety, especially for elderly patients who cannot undergo intensive chemotherapy.
    Keywords:  HD‐MTX; PCNSL; RLZT; first‐line treatment
    DOI:  https://doi.org/10.1111/bjh.70335
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