bims-hemali 2026-01-18 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2026–01–18
33 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Marginal Zone Lymphoma: Phase 1/2 BRUIN Study.
Randomized phase 3 trial of Ropeginterferon alfa-2b versus surveillance after tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia (ENDURE/CML-IX).
Time to say adieu to FISH in myeloma diagnostics.
An Overview of Chronic Myeloid Leukemia Treatment: From Tyrosine Kinase Inhibitors to Novel and Emerging Therapies.
Efficacy and safety of subcutaneous mosunetuzumab in combination with lenalidomide and as a monotherapy in Japanese patients with relapsed/refractory follicular lymphoma.
Ponatinib for CML patients in routine clinical practice: the PONDEROSA study.
Impact of Bone Marrow Fibrosis on the Outcome of Chronic Myeloid Leukemia Treated with Second Generation Tyrosine Kinase Inhibitors.
Dose-dense chemotherapy enables elimination of RT for majority of low-risk pediatric Hodgkin lymphoma: PHC study HOD08.
First-line tagraxofusp leads to durable responses and prolonged survival in adults with blastic plasmacytoid dendritic cell neoplasm regardless of fitness level.
Phase 1B pilot study of itacitinib with alemtuzumab in patients with T-cell prolymphocytic leukemia.
Approaches to the management of relapsed/refractory mantle cell lymphoma: navigating an increasingly complex therapeutic landscape.
Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study.
Hypomethylating agents in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS): A systematic review.
Quantitative MYD88L265P and CXCR4S338X analysis to assess clinical trial performance in Waldenstrom Macroglobulinemia.
Risk factors and reasons for switching from front-line therapy in the Italian chronic myeloid leukaemia network: A cohort study.
Idiopathic Multicentric Castleman Disease-TAFRO: A Potentially Curable Disease?
Disordered differentiation and cellular senescence in pediatric Hodgkin Reed-Sternberg cells.
Immunotherapies in chronic immune-mediated neuropathies.
Treatment Outcomes of Elderly Patients with Mantle Cell Lymphoma: A Multi-center Real-World Data.
Evaluating inflammatory markers in distinguishing polycythemia Vera from secondary polycythemia: a prospect for novel diagnostic marker.
CD34-positive circulating cells quantification during follow-up in myeloproliferative neoplasms.
Survival and Renal Recovery in Newly Diagnosed Multiple Myeloma Patients Presenting With Dialysis-Requiring Severe Renal Impairment.
Paediatric blastic plasmacytoid dendritic cell neoplasm: a single-centre case series of 18 children and review of the literature.
Iron Deficiency Anemia.
Warm autoimmune haemolytic anaemia: Clinical considerations.
Hydroxyurea pharmacokinetics, it is a small world after all.
Exercise-Mobilized Lymphocytes Enhance the Function of Cytokine-Induced Memory-like NK-cells Against Myeloid Leukemia.
VEXAS syndrome: a comprehensive review of pathogenesis, clinical spectrum, and therapeutic strategies.
Trust is a verb: how to reimagine confidence in health systems.
Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.
Bulky Auricular Folliculotropic Mycosis Fungoides: Dramatic Response and Rechallenge Efficacy With Extended Brentuximab Vedotin Therapy.
Models of myeloma bone disease: In vivo and in vitro approaches.
[Extramedullary blast crisis limited to the lymph nodes in chronic myeloid leukemia with a T/myeloid mixed phenotype].

Blood Adv. 2026 Jan 16. pii: bloodadvances.2025017489. [Epub ahead of print]

Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Marginal Zone Lymphoma: Phase 1/2 BRUIN Study.

Krish Patel, Julie M Vose, Sunita D Nasta, Jennifer R Brown, Kami J Maddocks, Jennifer A Woyach, Nirav N Shah, Bita Fakhri, Benoit Tessoulin, Shuo Ma, Deepa Jagadeesh, Ewa Lech-Maranda, Catherine C Coombs, Manish R Patel, Joanna M Rhodes, Chaitra S Ujjani, Marc S Hoffmann, Chan Y Cheah, Talha Munir, David John Lewis, Lydia Scarfò, Toby A Eyre, Alvaro J Alencar, Jonathon B Cohen, Andrew D Zelenetz, Donald E Tsai, Mei Li, Yuanyuan Bian, Paolo B Abada, Minna Balbas, Pier Luigi Luigi Zinzani.

Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies that have a natural history that follows a remitting and relapsing course. For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy with or in combination with chemotherapy (chemoimmunotherapy), with second-line options such as covalent (c) Bruton tyrosine kinase inhibitors (BTKi). However, management of relapsed and refractory (R/R) MZL remains a challenge. Pirtobrutinib, a highly selective, non-covalent BTKi has shown promising efficacy and tolerability in patients with poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here we report the safety and efficacy of pirtobrutinib in patients with MZL from the phase 1/2 BRUIN study. Endpoints included investigator assessed ORR by Lugano 2014 criteria, DOR, PFS, OS, and safety. Among 36 R/R MZL patients (EMZL: n=6; NMZL: n=17; SMZL: n=13), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10) including anti-CD-20 antibody (100%), chemotherapy (86%) and cBTKi therapy (72%). The ORR was 55.6% (95% confidence interval [CI], 38.1- 72.1) including 3 (8.3%) complete responses and 17 (47.2%) partial responses. Median DOR was 17.8 months (95%CI, 7.4-non-estimable [NE]), and median PFS was 16.6 months (95%CI, 9.0-22.1). With median follow-up of 32.4 months (IQR, 28.0, 41.3), median OS was NE (95%CI, 29.5-NE). The ORR for patients with prior cBTKi therapy was 53.8% (95%CI, 33.4-73.4). Pirtobrutinib was well-tolerated with dose reductions in 4 patients (11.1%) and permanent discontinuation due to TEAEs in 4 (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pre-treated R/R MZL, including prior cBTKi. NCT03740529.

DOI: https://doi.org/10.1182/bloodadvances.2025017489
Leukemia. 2026 Jan 12.

Randomized phase 3 trial of Ropeginterferon alfa-2b versus surveillance after tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia (ENDURE/CML-IX).

Andreas Burchert, Franck E Nicolini, Philipp le Coutre, Susanne Saussele, Andreas Hochhaus, Evin Tuere, Stephan K Metzelder, Kim Pauck, Holger Garn, Hartmann Raifer, Magdalena Huber, Norbert Gattermann, Martina Crysandt, Philippe Schafhausen, Matthias Bormann, Markus P Radsak, Agnès Guerci-Bresler, Thomas Illmer, Maria E Goebeler, Peter Herhaus, Lino L Teichmann, Georg-Nikolaus Franke, Fabian Lang, Stefan W Krause, Robert Möhle, Martine Klausmann, Frank Stegelmann, Christoph Lutz, Gabriel Etienne, Andrea Stoltefuß, Joachim R Göthert, Thomas Ernst, Maisun Abu-Samra, Heinz-Gert Höffkes, Andreas Neubauer, Ying Wang, Paul Weiland, Clara Otto, Lea Kiessler, Theresa Weber, Lea Kroning, Andrea Nist, Thorsten Stiewe, Rüdiger Hehlmann, Behnaz Aminossadati, Michael Wittenberg, Kerstin Winterstein, Thomas Oellerich, Marcus Lechner, Markus Pfirrmann, Carmen Schade-Brittinger, Paul Klemm, Christian Michel.

Treatment-free remission (TFR) after discontinuation of ABL tyrosine kinase inhibitors (TKIs) is an important therapeutic goal in chronic myeloid leukemia (CML). Interferon-α (IFN) has been suggested to promote durable TFR. The phase 3 ENDURE trial (NCT03117816; EUDRA-CT 2016-001030-94) prospectively tested this hypothesis in patients with stable deep molecular remission after TKI therapy. A total of 203 patients were randomised 1:1 to receive ropeginterferon alfa-2b (ropeg-IFN; 100 µg subcutaneously every two weeks for 15 months, n = 95) or observation alone (n = 108) after TKI discontinuation. The primary endpoint was molecular relapse-free survival (MRFS), defined as time to loss of major molecular response (MMR) or death. At a median follow-up of 36 months, 25-month MRFS was 56% (95% confidence interval (CI), 45-66) with ropeg-IFN and 59% (95% CI, 49-68) with observation (hazard ratio (HR), 1.02; 95% CI, 0.68-1.55; P = 0.91). Among 83 patients with molecular data after TKI restart, 79 (95%) regained at least MMR, 78 within 12 months (median 3 months, interquartile range: 2-4 months). Ropeg-IFN was well tolerated (median administered dose of 92 µg, range 3-104), and no new safety signals were observed. Ropeg-IFN maintenance did not improve the probability of sustained TFR after TKI discontinuation.

DOI: https://doi.org/10.1038/s41375-025-02859-1
Blood. 2026 Jan 15. 147(3): 221-222

Time to say adieu to FISH in myeloma diagnostics.

Juan-Jose Garces, Francesco Maura.

DOI: https://doi.org/10.1182/blood.2025031255
Eur J Haematol. 2026 Jan 13.

An Overview of Chronic Myeloid Leukemia Treatment: From Tyrosine Kinase Inhibitors to Novel and Emerging Therapies.

Akash Joel Sekar, Sanjay Sakthivel, Abilash Valsala Gopalakrishnan, Rahul Vashishth, Reshma Murali.

  The Philadelphia chromosome and its linked BCR-ABL1 fusion gene, which causes aberrant tyrosine kinase activity, make chronic myeloid leukemia (CML) a model for molecularly targeted cancer treatment. Although the yearly incidence in the United States remains steady at approximately 2 per 100 000 people, the advent of tyrosine kinase inhibitors (TKIs) has significantly altered the disease landscape. TKIs have greatly improved patient outcomes and reframed CML as a chronic, treatable illness. Nevertheless, the healthcare industry has to come up with new ways to improve patient adherence, reduce side effects, and get past medication resistance. The pathophysiology of CML and the development of TKI-based treatments, including first-, second-, and third-generation medicines, are thoroughly examined in this study. We also focus on the side effect profiles, comparative clinical efficacy, and mechanisms of action, with a focus on patient-centered treatment choices. We also discuss the critical evaluation of the intricacy of TKI resistance, intolerance, and the objective of treatment-free remission. Additionally, the development of new therapeutic approaches is examined as a forward-looking tactic to produce more profound and long-lasting molecular responses which include immune-based therapies, combinatorial approaches, and promising third-generation TKIs. This review aims to improve patient outcomes and identify future avenues in CML research by combining new information with existing knowledge.

Keywords:  BCR‐ABL1; CML treatment; chronic myeloid leukemia; novel therapies; tyrosine kinase inhibitors

DOI:  https://doi.org/10.1111/ejh.70110
Int J Clin Oncol. 2026 Jan 12.

Efficacy and safety of subcutaneous mosunetuzumab in combination with lenalidomide and as a monotherapy in Japanese patients with relapsed/refractory follicular lymphoma.

Shinichi Makita, Koji Izutsu, Yuko Mishima, Takahiro Kumode, Junya Kuroda, Nobuhiro Kanemura, Noriko Fukuhara, Kazuyuki Shimada, Chiemi Mori, Atsuko Kawasaki, Takeshi Miyake, Dai Maruyama.

   BACKGROUND: JO40295 (jRCT2080223801) evaluated the efficacy and safety of subcutaneous (SC) mosunetuzumab, in combination with lenalidomide and as monotherapy, in Japanese patients with relapsed/refractory (R/R) follicular lymphoma (FL). We report outcomes from the interim analysis of the FLMOON-2 (≥ 1 prior therapy; mosunetuzumab plus lenalidomide) and primary analysis of the FLMOON-3 (≥ 2 prior therapies; mosunetuzumab monotherapy) cohorts.
METHODS: Mosunetuzumab SC was administered with Cycle (C)1 step-up dosing in both cohorts: C1 Day (D)1, 5 mg; C1D8, D15 and C2 onwards, 45 mg. In FLMOON-2, oral lenalidomide was administered from C2 onwards, on D1-21 of each cycle. Treatment was administered up to C12 in FLMOON-2 and C8 or C17 in FLMOON-3. The primary endpoint was independent review facility-assessed complete response (CR) rate.
RESULTS: At the clinical cut-off date (FLMOON-2: April 4, 2024; FLMOON-3: March 4, 2024), in the efficacy-evaluable populations, CR rate was 92.3% in FLMOON-2 (n = 13) and 100% in FLMOON-3 (n = 5). In the safety-evaluable populations (FLMOON-2, n = 17; FLMOON-3, n = 5), Grade 3/4 adverse events (AEs) occurred in 64.7% of patients in FLMOON-2 and 20.0% in FLMOON-3. No Grade 5 AEs or AEs leading to treatment discontinuation occurred in either cohort. Cytokine release syndrome was reported in 47.1% of patients in FLMOON-2 and 20.0% in FLMOON-3. Serum mosunetuzumab concentration peaked with the third dose of mosunetuzumab in C1 and reached a steady state with repeated dosing.
CONCLUSION: Mosunetuzumab SC, in combination with lenalidomide and as monotherapy, demonstrated promising efficacy with a manageable safety profile in Japanese patients with R/R FL.

Keywords:  Bispecific antibodies; Follicular lymphoma; Japan ; Lenalidomide; Mosunetuzumab; Subcutaneous

DOI:  https://doi.org/10.1007/s10147-025-02957-1
Ann Hematol. 2026 Jan 15. 105(1): 9

Ponatinib for CML patients in routine clinical practice: the PONDEROSA study.

German CML Study Group and the Czech Leukemia Study Group

  Ponatinib, a third-generation tyrosine kinase inhibitor, is effective in patients with chronic myeloid leukemia (CML), particularly in cases of resistance or BCR::ABL1 T315I mutation. However, arterial occlusive events (AOEs) remain an important safety concern. The PONDEROSA registry evaluated ponatinib use under routine clinical conditions in Germany and the Czech Republic. This observational cohort study included 99 adult CML patients treated with ponatinib; patient recruitment took place between 2015 and 2022 at 31 centers. The median follow-up was 22 months (range: 1-83). Among the 99 patients (median age 54 years at CML diagnosis), 91.9% were in chronic phase, 4.0% in accelerated phase, and 4.0% in blast phase. The T315I BCR::ABL1 mutation was detected in 19.2%. Ponatinib starting doses were 45 mg/day (32.3%), 30 mg/day (37.3%), or 15 mg/day (29.3%). Adverse events (AEs) were recorded in 64.6% of patients. Severe cardiovascular or cerebrovascular events occurred in 12.1% of patients, with no fatal events observed. Ponatinib was discontinued in 31.3% of patients, mainly due to intolerance or lack of response. 58.6% of patients achieved or maintained at least a major molecular response (MMR), compared to 19.0% at baseline. Disease progression was observed in 14.1% of patients, and 8.1% underwent allogeneic stem cell transplantation. The estimated 2-year progression-free survival and overall survival rates were 84.4% and 85.7%, respectively. The PONDEROSA study confirms the clinical effectiveness of ponatinib in routine practice. Individualized dosing strategies are essential to balance efficacy and cardiovascular safety. Ponatinib remains a valuable bridging therapy for patients requiring allogeneic transplantation.

Keywords:  Arterial occlusive events; Chronic myeloid leukemia; Dose optimization; Ponatinib; Real-world evidence; Registry

DOI:  https://doi.org/10.1007/s00277-026-06788-6
Indian J Hematol Blood Transfus. 2026 Jan;42(1): 120-125

Impact of Bone Marrow Fibrosis on the Outcome of Chronic Myeloid Leukemia Treated with Second Generation Tyrosine Kinase Inhibitors.

Faiqa Fayyaz, Waseem Shahani, Nida Anwar, Kabeer Guriro, Muhammad Nizamuddin, Aisha Arshad, Uzma Zaidi.

  Chronic myeloid leukemia (CML) is characterized by the BCR-ABL1 fusion oncogene, leading to increased tyrosine kinase activity. The current study was aimed to evaluate the impact of bone marrow fibrosis on the clinical outcomes of CML patients treated with second-generation tyrosine kinase inhibitor(TKI) among patients in Pakistan. A longitudinal study was conducted at National Institute of Blood Disease and Bone Marrow Transplantation (NIBD-BMT), Karachi, from October 2022 to October 2023. A total of 150 CML patients aged 18-80 years receiving second generation TKI were included. BM fibrosis was graded according to WHO criteria. Outcomes such as complete hematological response (CHR) and major molecular response (MMR) were evaluated at 3 and 6 months. Data were analyzed using SPSS version 25, with p-value of < 0.05. The median age of patients was 43.5 years, with male predominance (60.7%). BM fibrosis was present in 69.3% of patients at diagnosis. Patients with lower fibrosis grades (MF 0-1) had significantly higher rates of CHR at 3 months (73.5%) and MMR at 6 months (64.7%) compared to those with higher grade fibrosis (MF 2-3) with CHR of 66.7% and MMR of 50%. Optimal response rates were also higher in lower fibrosis grades (77.4% vs. 56.2%). Moreover, treatment failure was common with higher fibrosis grade. BM fibrosis is a critical factor influencing the response to TKIs in CML patients. Lower grades of fibrosis correlate with higher response rates and better clinical outcomes, suggesting the importance of early intervention and tailored treatment approaches based on fibrosis grading.

Keywords:  Bone marrow fibrosis; Chronic myeloid leukemia; Complete hematological response; Major molecular response; Tyrosine kinase inhibitors

DOI:  https://doi.org/10.1007/s12288-025-01987-z
Blood. 2026 Jan 13. pii: blood.2025029535. [Epub ahead of print]

Dose-dense chemotherapy enables elimination of RT for majority of low-risk pediatric Hodgkin lymphoma: PHC study HOD08.

Jamie E Flerlage, Angela M Feraco, Yiwang Zhou, Ying Zheng, Jia Liang, John T Lucas, Alison M Friedmann, Howard J Weinstein, Torunn I Yock, Barry L Shulkin, Sue C Kaste, Lianna J Marks, Matthew J Ehrhardt, Stephanie B Dixon, Scott Howard, Pedro de Alarcon, Sandra Luna-Fineman, Amy E Geddis, Eric C Larsen, Karen J Marcus, Amy Billett, Sarah S Donaldson, Melissa M Hudson, Monika L Metzger, Matthew J Krasin, Michael P Link.

The Pediatric Hodgkin Consortium (PHC) hypothesized that increasing chemotherapeutic dose-density for Hodgkin lymphoma (HL) they could increase the complete response rate among favorable risk patients with HL after 8 weeks of Stanford V compared to 8 weeks of VAMP. This would translate to a decrease in patients who required radiation therapy (RT) to achieve a cure. HOD08 (NCT00846742) was a phase II multicenter investigator-initiated single- arm trial for patients ≤ 21 years of age with previously untreated stage IA or IIA HL without mediastinal bulk or extranodal disease extension and fewer than three sites of disease. Treatment consisted of a modified 8-week Stanford V regimen (vinblastine, doxorubicin, vincristine, bleomycin, mechlorethamine, etoposide and prednisone). Modified tailored field RT was administered only to disease sites achieving less than a CR. The primary objective was to increase CR rate after 8 weeks of chemotherapy by at least 20% (from an estimated 44% to 64%) compared to patients treated on a previous trial (HOD99). HOD08 enrolled 85 patients with HL and 72 were evaluable for the primary objective of whom 55 (76.4%) achieved a CR at all sites and did not receive RT. The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 87.4% (95% confidence interval (CI) 80.4%-95.0%) and 98.7% (95% CI 96.2%-100%), respectively. A dose-dense modified Stanford V regimen reduced the proportion of low-risk pediatric patients with HL who received RT while maintaining excellent outcomes. NCT00846742.

DOI: https://doi.org/10.1182/blood.2025029535
Haematologica. 2026 Jan 15.

First-line tagraxofusp leads to durable responses and prolonged survival in adults with blastic plasmacytoid dendritic cell neoplasm regardless of fitness level.

Naveen Pemmaraju, Marco Herling, Kendra L Sweet, Anthony S Stein, Sumithira Vasu, Todd L Rosenblat, David A Rizzieri, Cristina Papayannidis, Eunice S Wang, Marina Konopleva, Michael Zuurman, Alessandra Tosolini, Muzaffar Qazilbash, Andrew A Lane.

Not available.

DOI: https://doi.org/10.3324/haematol.2025.300036
Blood Neoplasia. 2026 Feb;3(1): 100175

Phase 1B pilot study of itacitinib with alemtuzumab in patients with T-cell prolymphocytic leukemia.

Tapan M Kadia, Akhil Jain, Caitlin R Rausch, Alex Bataller, Farhad Ravandi, Elias Jabbour, Wei Qiao, Gautam Borthakur, Nicholas Short, Guillermo Montalban-Bravo, Andres E Quesada, Jan Burger, Alessandra Ferrajoli, William Wierda, Chitra Hosing, Hagop Kantarjian.

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and platelet >30 × 103/μL. Cycle 1 included a lead-in phase with itacitinib monotherapy days 1-14. Beginning day 15, patients also received alemtuzumab 30mg IV 3 times weekly for up to 4 (28-day) cycles or until best response. At best response, up to 8 cycles of maintenance with single-agent itacitinib was allowed. Median age was 65 years (range, 39-83). Ten patients (67%) had complex cytogenetics, 11 (73%) had chromosome 14 abnormality, and 13 (87%) were TCL1A positive by fluorescence in situ hybridization. Among frontline patients, overall response rate (ORR) was 88% (complete remission [CR]: 75%), median event-free survival (EFS) and overall survival (OS) were 11.6 and 19.5 months, respectively. Three frontline patients proceeded to allogeneic stem cell transplantation. The ORR in the relapsed/refractory cohort was 57% (CR: 43%), whereas median EFS and OS were 11.1 months. Most (85%) adverse events were grade 1 to 2 and none were attributed to itacitinib. Continued studies evaluating JAK inhibitors in patients with T-PLL are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03989466.

DOI: https://doi.org/10.1016/j.bneo.2025.100175
Expert Rev Hematol. 2026 Jan 11.

Approaches to the management of relapsed/refractory mantle cell lymphoma: navigating an increasingly complex therapeutic landscape.

Wan Danial Noor, Diego Villa, Chan Yoon Cheah.

   INTRODUCTION: Mantle cell lymphoma (MCL) represents a distinct subtype of mature B-cell lymphoma, considered incurable with a pattern of recurrent relapses and suboptimal responses to subsequent therapies that portends poorer prognosis with each recrudescent disease.
AREAS COVERED: Covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have transformed the relapsed/refractory (R/R) MCL landscape as monotherapy but may emerge to be more effective as combinations with B-cell lymphoma-2 (BCL-2) inhibitors and immunotherapy. Immune-leveraging therapies, including chimeric antigen receptor (CAR) T-cell therapy and T-cell engaging antibodies are gaining momentum, with the former demonstrating durable responses in a subset of patients while the latter being evaluated in various combination regimens. Allogeneic hematopoietic stem cell transplants remain a potentially curative option for selected patients.
EXPERT OPINION: This review seeks to navigate this increasingly complex therapeutic landscape while providing a suggested treatment and sequencing algorithm that may be tailored to individual patients.

Keywords:  CAR T; MCL; Mantle cell lymphoma; Non-covalent BTK inhibitor; bispecific; expert opinion; recent advances; refractory; relapsed; review

DOI:  https://doi.org/10.1080/17474086.2026.2613730
Hemasphere. 2026 Jan;10(1): e70287

Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study.

Meral Beksac, Tulin Fıratlı Tuglular, Francesca Gay, Roberto Mina, Eirini Katodritou, Ali Unal, Michele Cavo, Guner Hayri Ozsan, Vincent H J van der Velden, Berna H Beverloo, Michael Vermeulen, Mark van Duin, Guldane Cengiz Seval, Omur Gokmen Sevindik, Serena Merante, Kyriaki Manousou, Peter Sonneveld, Elena Zamagni, Evangelos Terpos.

Novel therapies are needed for patients with multiple myeloma (MM) and extramedullary plasmacytomas. The prospective, Phase II EMN19 study assessed the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone (DaraVCD) in 40 patients with newly diagnosed MM (NDMM; n = 29) or at first relapse (RMM; n = 11) and positron emission tomography or computed tomography (PET/CT)-confirmed extramedullary plasmacytomas (extraosseous [EMD] and/or paraosseous [PS]). DaraVCD was administered until disease progression or up to 3 years. The primary endpoint was hematological complete response (CR). Among patients, 22 (55.0%), 4 (10.0%), and 14 (35.0%) had EMD, EMD/PS, and PS plasmacytomas, respectively. Median patient age was 58.0 years, and 16 (40.0%), 12 (30.0%), and 10 (25.0%) patients were at International Staging System (ISS) Stages I, II, and III, respectively. Median circulating tumor cell (CTC) level was 0.002% (range, 0.000-0.353), significantly higher (P < 0.05) in patients with ISS Stage III and those with plasma cells > 60%. At a median follow-up of 30.0 months, all patients completed treatment (median duration: 19.8 months). The overall hematologic ≥CR rate was 47.5% (19/40; NDMM patients: 58.6% [17/29]; RMM patients: 18.2% [2/11]). Of patients with ≥CR, 80.0% (15/19) achieved minimal residual disease (MRD) negativity, and 68.4% (13/19) combined MRD negativity and complete metabolic response (CMR) on PET/CT. The overall median progression-free survival was 25.8 months, significantly longer in patients achieving hematologic ≥CR and/or CMR than others (not reached and 4.8 months, respectively; P < 0.001). DaraVCD showed encouraging efficacy in patients with MM and extramedullary plasmacytomas. Notably, this is the first report on CTC levels in EMD, and they were lower than previously reported NDMM thresholds.

DOI: https://doi.org/10.1002/hem3.70287
Br J Haematol. 2026 Jan 14.

Hypomethylating agents in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS): A systematic review.

Fieke W Hoff, Roochi Trikha, Emma M Groarke, Bhavisha A Patel.

  VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an X-linked, systemic, haemato-inflammatory syndrome caused by somatic mutations in the UBA1 gene. No standardized treatment guidelines exist, but evidence is emerging that treatment with hypomethylating agents (HMAs) can induce improvement of the inflammatory symptoms, reverse cytopenia, enable weaning of the corticosteroids and, in some cases, induce molecular remission. We systematically reviewed the literature to evaluate the experience with HMA in the management of VEXAS, following 2020 PRISMA guidelines across three databases. A total of 30 citations reporting 166 patients with genetically confirmed VEXAS syndrome treated with HMA were included. All but three patients were males (98%), and the median age was 71 years (range, 29-86). Inflammatory symptoms (96% of patients), constitutional symptoms (84%) and cytopenia (89%) were most frequently reported, and 81% had a concomitant diagnosis of myelodysplastic syndromes (MDS). Most mutations were substitutions of p.Met41 (81%). Overall inflammatory response was achieved in 59% of treated patients with most complete response (52%). Responses were documented in patients with and without concomitant MDS. Any haematological response was achieved in 74% of the patients, and eradication of the UBA1 clone (to a variant allele fraction of <2%) was detected in 51% of cases in whom mutation testing was performed (n = 32/63). Toxicity was the most frequent reason for discontinuation of therapy. This review highlights HMAs as a feasible option in the management of VEXAS syndrome. Prospective studies are needed to identify predictors for response or resistance and optimal regimens.

Keywords:  UBA1; VEXAS; azacitidine; hypomethylating agent

DOI:  https://doi.org/10.1111/bjh.70302
Blood Adv. 2026 Jan 16. pii: bloodadvances.2025018605. [Epub ahead of print]

Quantitative MYD88L265P and CXCR4S338X analysis to assess clinical trial performance in Waldenstrom Macroglobulinemia.

Nickolas Tsakmaklis, Zachary R Hunter, Xia Liu, Amanda Kofides, Shirong Liu, Maria Luisa Guerrera, Alberto Guijosa, Hao Sun, John M Hatcher, Abigail Peachey, Christopher J Patterson, Kirsten E Meid, Joshua Gustine, Andrew R Branagan, Shayna Sarosiek, Jorge J Castillo, Steven P Treon.

DOI: https://doi.org/10.1182/bloodadvances.2025018605
Br J Haematol. 2026 Jan 11.

Risk factors and reasons for switching from front-line therapy in the Italian chronic myeloid leukaemia network: A cohort study.

Massimo Breccia, Valentina Giai, Tiziana Rosso, Patrizia Pregno, Fausto Castagnetti, Massimiliano Bonifacio, Isabella Capodanno, Mario Tiribelli, Fabio Stagno, Olga Mulas, Antonella Gozzini, Andrea Patriarca, Federica Sorà, Giuseppina Loglisci, Antonella Russo Rossi, Maria Rosaria Coppi, Maria Cristina Miggiano, Francesco Di Raimondo, Gianantonio Rosti, Fabrizio Pane, Giuseppe Saglio, Giovannino Ciccone, Giorgina Specchia.

  Identifying chronic myeloid leukaemia (CML) patients at risk of therapeutic switch remains debated. We analysed the cumulative risk of treatment change in the CML Italian network prospective cohort based on first-line tyrosine kinase inhibitors and patient characteristics. Sub-hazard ratios (sHRs) were estimated using Fine and Gray multivariable models. Among 1662 patients, initial treatment consisted of imatinib for 840 (50.5%), nilotinib for 490 (29.5%) and dasatinib for 332 (20.0%). Subsequently, 492 patients (29.6%) required second-line therapy, with 232 (47.1%) switching due to resistance and 176 (35.8%) due to intolerance. At 2 years, the risk of resistance was 18.3% for imatinib, 8.4% for dasatinib (sHR = 0.32; 95% confidence interval 0.21-0.49) and 6.8% for nilotinib (0.29; 0.19-0.42). The risk of switching increased in intermediate (1.95; 1.40-2.72) and high Eutos long term survival (ELTS) risk (3.19; 2.10-4.83) but was reduced with older age (0.97 per year; p < 0.0001). Intolerance at 2 years was 8.5% for imatinib, 12.4% for dasatinib (2.55; 1.73-3.75) and 5.2% for nilotinib (1.04; 0.65-1.65). Switching to a third-line therapy at 3 years was 8% for imatinib, 5% for dasatinib and 4% for nilotinib. The results showed that the time to first treatment switch for resistance is shorter for younger patients, for imatinib and for intermediate/high ELTS risks. The risk of switching for intolerance is higher for patients initially treated with dasatinib.

Keywords:  chronic myeloid leukaemia; prognosis; switch; tyrosine kinase inhibitors

DOI:  https://doi.org/10.1111/bjh.70332
Am J Hematol. 2026 Jan 10.

Idiopathic Multicentric Castleman Disease-TAFRO: A Potentially Curable Disease?

Lu Zhang, Jia-Ying Ge, Si-Yuan Li, Hong-Yan Tong, Liang-Shun You, Jian Li.

  Idiopathic multicentric Castleman disease (iMCD)-TAFRO (Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/renal dysfunction, Organomegaly) is the most severe clinical subtype of iMCD characterized by a catastrophic cytokine storm. Currently, iMCD-TAFRO is regarded as incurable which needs "indefinite" treatment. However, long-term data are sparse, and treatment discontinuation may be possible in a subset of patients. This multicenter, retrospective study analyzed 27 patients who discontinued treatment. All patients had biochemical complete response (CR) at the time of drug discontinuation. Most patients were treated with myeloma-like treatment (59.3%) and only 11.1% received anti-IL-6 therapy. With a median follow-up of 31 months (range, 12-108) after treatment discontinuation, only four patients (14.8%) suffered from progression of disease (PD) and the others (85.2%) maintained biochemical CR. Patients who suffered from PD had a significantly lower pretreatment CRP level than patients maintaining responses (43.7 ± 39.3 vs. 126.4 ± 62.5 mg/L, p = 0.018). No significant impacts of different treatment approaches or duration of treatment on the likelihood of achieving long-term remission were observed. The median time between drug discontinuation to PD (n = 4) was 9.5 months (range, 5-12). These patients all achieved treatment responses again with the same or similar treatment approaches. The estimated PFS at 6 months, 1 year, and 3 years were 96.3%, 85.2%, and 85.2%, respectively. All patients remained alive with a median of 31 months follow-up after drug discontinuation. This study suggests that some iMCD-TAFRO patients might maintain long-term remission after treatment discontinuation. For patients who achieved biochemical CR, an attempt at treatment discontinuation could be considered.

Keywords:  curable disease; drug discontinuation; iMCD‐TAFRO; idiopathic multicentric Castleman disease; long‐term remission

DOI:  https://doi.org/10.1002/ajh.70199
Blood Adv. 2026 Jan 15. pii: bloodadvances.2025016953. [Epub ahead of print]

Disordered differentiation and cellular senescence in pediatric Hodgkin Reed-Sternberg cells.

Jennifer E Agrusa, Elmoataz Abdel Fattah, Howard Lin, Jessica Velazquez, Sandra Andrea Salinas, Harshal A Abhyankar, Brooks P Scull, Ryan Fleischmann, M Tarek Elghetany, Andrea N Marcogliese, Choladda Vejabhuti Curry, Jyotinder Nain Punia, Nmazuo W Ozuah, Olive Simone Eckstein, Nader Kim El-Mallawany, Nitya Gulati, Joseph Lubega, Terzah M Horton, Kala Y Kamdar, Kenneth L McClain, Tsz-Kwong Man, Carl E Allen.

Hodgkin lymphoma (HL) is characterized by inflammatory lesions with relatively few (typically < 1%) pathogenic Hodgkin Reed-Sternberg (HRS) cells. The scarcity of malignant HRS cells in HL has historically limited characterization of these disease drivers, and pathogenic mechanisms underlying HL are incompletely defined. Using multi-parameter flow cytometry to purify HRS cells and immune cell populations from pediatric HL lesions and control tonsils, we sought to define transcriptional programs in pediatric HRS cells. HRS cells are thought to arise from transformed germinal center B cells. Interestingly, transcriptomic analysis of HRS cells compared to control tonsil CD30+ cells revealed disordered differentiation with multi-lineage gene expression patterns, and primary HRS cells had distinct transcriptomes compared to HL cell lines. Further, transcriptomic analysis revealed increased expression of senescence-related genes and downregulation of pro-apoptotic/mitosis-related genes. Gene expression findings were validated by immunohistochemistry and single cell imaging. In vitro treatment of primary HRS cells with BCL2 inhibitor, venetoclax, augmented induction of apoptosis in HRS cells and other cells of the HL immune microenvironment. These findings support further study of targeting apoptosis resistance as a potential approach to eliminate malignant HRS cells and dismantle inflammatory lesion formation in pediatric HL.

DOI: https://doi.org/10.1182/bloodadvances.2025016953
Handb Clin Neurol. 2026 ;pii: B978-0-323-90887-0.00019-5. [Epub ahead of print]214 345-356

Immunotherapies in chronic immune-mediated neuropathies.

Chiara Briani, Andrea Visentin.

  Steroids and immunoglobulins, either intravenous or subcutaneous, have represented the cornerstone treatment of chronic immune-mediated neuropathies for many years. In the last decade, new therapeutic targets are being studied, with the potential to selectively dampen aberrant immune responses, including drugs that act both on the complement pathways and the recycling mechanism of IgG immunoglobulins by the neonatal receptor (FcRn). Among the latter, efgartigimod has recently been approved for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Also rituximab, an anti-CD20 monoclonal antibody mostly used in antimyelin-associated glycoprotein (MAG) antibody neuropathy and in autoimmune nodo-paranodopathies, has been tested both in open and double-blind studies in CIDP, whereas ARGX-117, an antibody targeting the C2 fraction of the complement, is under investigation in multifocal motor neuropathy. In anti-MAG antibody neuropathy, Bruton's tyrosine kinase inhibitors, zanubrutinib and acalabrutinib, are currently tested either as a single agent or in combination with rituximab.

Keywords:  Anti-MAG neuropathy; BTK inhibitor; CIDP; Chronic immune-mediated neuropathies; Efgartigimod; FcRn; Multifocal motor neuropathy; Paraproteinemic neuropathy; Rituximab

DOI:  https://doi.org/10.1016/B978-0-323-90887-0.00019-5
Indian J Hematol Blood Transfus. 2026 Jan;42(1): 82-92

Treatment Outcomes of Elderly Patients with Mantle Cell Lymphoma: A Multi-center Real-World Data.

Ebru Kilic Gunes, Filiz Yavasoglu, Selin Kucukyurt, Fatma Aykas, Sureyya Yigit Kaya, Munevver Irem Kok Yilmaz, Murat Yildirim, Neslihan Andic, Ahmet Kursad Gunes, Volkan Karakus, Omur Gokmen Sevindik, Zubeyde Nur Ozkurt, Eren Gunduz, Meltem Ayli.

  Mantle Cell Lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma (NHL), accounting for 5-7% of all lymphomas. Currently, there is no standardized treatment option for older patients (> 65 years), and optimizing MCL treatment in this group remains a significant clinical challenge. In this multicenter retrospective study, we aimed to evaluate the outcomes of first-line treatments, overall survival (OS), progression-free survival (PFS), and factors influencing survival in patients aged 65 years and older diagnosed with MCL. Patients aged ≥ 65 years diagnosed with MCL between November 2016 and January 2024 in six centers were included in this study. A total of 77 patients were included in the study, with 60 males (77.9%) and 17 females (22.1%). The median age was 71 years (range: 65-89). At diagnosis, 96.1% of patients had Stage III-IV disease, and 36.4% had an ECOG performance score of 2-3. Based on the MIPI-c score, 48% of patients had high-risk disease. As induction chemotherapy, 44.2% received R-CHOP, 13% received RB, 13% received R-CVP, and 29.8% received alternating R-CHOP/R-DHA-platinum. Additionally, 19.5% of patients underwent ASCT, and 28.6% received Rituximab maintenance after induction therapy or ASCT. The overall response rate (ORR) was 71.4%. After a median follow-up of 32 months, the median PFS was 18 months, and the median OS was 42 months. In multivariate analysis, independent risk factors for inferior PFS were LDH > ULN (HR: 2.09, 95% CI: 1.05-4.16, p = 0.035), Ki67 ≥ 30% (HR: 2.90, 95% CI: 1.38-6.10, p = 0.005), blastoid variant (HR: 1.86, 95% CI: 1.09-5.12, p = 0.040), and maintenance treatment (HR: 0.31, 95% CI: 0.12-0.75, p = 0.010). Independent risk factors for inferior OS were the maintenance treatment (HR: 0.29, 95% CI: 0.09-0.94, p = 0.040) and POD24 (HR: 2.04, 95% CI: 1.06-4.19, p = 0.044). There remains no universally accepted standard treatment for older MCL patients, and the disease remains incurable with current treatment modalities. However, advancements in targeted therapies and the optimization of maintenance strategies hold promise for improving survival in older and unfit patients. Future studies focusing on incorporating targeted therapies into first-line treatment and identifying high-risk factors that influence survival will be crucial in tailoring effective and individualized treatment approaches for this population.

Keywords:  Elderly; Mantle cell lymphoma

DOI:  https://doi.org/10.1007/s12288-025-01979-z
Ann Hematol. 2026 Jan 15. 105(1): 13

Evaluating inflammatory markers in distinguishing polycythemia Vera from secondary polycythemia: a prospect for novel diagnostic marker.

Mohammad Navid Khaksari, Kimia Oraei Sajjadi, Fatemeh Arianmanesh, Hossein Ayatollahi, Samaneh Boroumand-Noughabi.

  Polycythemia vera (PV) is a myeloproliferative neoplasm. The presence of JAK2 mutations is a major diagnostic criterion for PV. PV is linked to chronic inflammation and an increased risk of thrombosis, and inflammation plays a significant part in the pathophysiology of PV. Testing for JAK2 mutations is expensive and is not available in all laboratories. Simple inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are evaluated in this study as potential diagnostic markers for differentiating patients with PV from other patients with polycythemia. We conducted a retrospective study of the clinical and laboratory data from 281 patients with polycythemia (110 with PV and 181 with secondary polycythemia (SP)) who attended Ghaem Hospital. The diagnosis of PV was established based on the World Health Organization criteria. Individuals who did not meet the criteria were classified as having SP. The median NLR, PLR, and SII in the PV group were considerably elevated compared to the SP group (NLR: 5.00 vs. 1.86, PLR: 261.3 vs. 94.0, SII: 2432.9 vs. 368.8, p < 0.001 for all). The receiver operating characteristic analysis revealed that NLR, PLR, and SII were highly effective in differentiating PV patients from the SP group. Each of these tests showed sensitivities and specificities over 85% and an area under the curve of more than 0.9. SII, NLR, and PLR were all higher in PV than SP, suggesting that these biomarkers, particularly SII, might be helpful in the diagnosis of PV.

Keywords:  Neutrophil-to-lymphocyte ratio; Platelet-to-lymphocyte ratio.; Polycythemia vera; Secondary polycythemia; Systemic inflammation index

DOI:  https://doi.org/10.1007/s00277-026-06787-7
Ann Hematol. 2026 Jan 16. 105(1): 21

CD34-positive circulating cells quantification during follow-up in myeloproliferative neoplasms.

Marine Demoy, Maxence Bauvais, Agathe Vely, Thomas Nicol, Jérémie Riou, Hortense Le Jeanne, Aurélien Bauduin, Hubert Rambaud, Françoise Boyer, Franck Geneviève, Agathe Boussaroque, Marie-Christine Copin, Valérie Ugo, Corentin Orvain, Damien Luque Paz.

  Polycythemia vera (PV) and Essential thrombcythemia (ET) are myeloproliferative neoplasms (MPNs) that can progress to secondary myelofibrosis, a complication associated with increased mortality. Circulating CD34-positive cells at diagnosis can be used to distinguish primary myelofibrosis from other MPNs with a threshold of 10/µL. In this study, we evaluate the interest of serial CD34-positive cell quantifications during the follow-up of MPNs. We retrospectively include 180 patients with MPN (90 ET, 55 PV and 35 myelofibrosis) with at least two measurements of circulating CD34-positive cells. CD34-positive cell count showed an AUC of 0.901 for the diagnosis of post-ET/PV myelofibrosis, with a sensitivity of 54.8%, a specificity of 99.5%, a PPV of 89.5% and a NPV of 96.3% for the threshold of 15 cells/µL. The decreased sensibility could be explained by an impact of cytoreductive treatments. Then we focused on primary and secondary myelofibrosis (MF) and found that patients achieving partial or complete response (per IWG-MRT criteria) had lower CD34-positive cell levels. Finally, CD34-positive cell levels had a prognostic impact on overall survival in MF, a count ≥ 100/µL is predictive of a higher risk of death (HR = 2.9 [1.5-5.9]), independently of DIPSS classification. In conclusion, monitoring of circulating CD34-positive cells is valuable for evaluating both disease progression and prognosis in MPN patients.

Keywords:  CD34-positive cell; Myelofibrosis; Myeloproliferative neoplasms

DOI:  https://doi.org/10.1007/s00277-026-06755-1
Eur J Haematol. 2026 Jan 14.

Survival and Renal Recovery in Newly Diagnosed Multiple Myeloma Patients Presenting With Dialysis-Requiring Severe Renal Impairment.

Rintu Sharma, Eshetu G Atenafu, Esther Masih-Khan, Harjot Vohra, Sita Bhella, Christine Chen, Vishal Kukreti, Guido Lancman, Anca Prica, A Keith Stewart, Rodger Tiedemann, Suzanne Trudel, Chloe Yang, Donna Reece.

   BACKGROUND: Severe renal insufficiency requiring dialysis in newly diagnosed multiple myeloma (NDMM) patients has been independently associated with poor survival outcomes. However, there is a paucity of data on factors predicting renal recovery and survival outcomes of these patients.
METHODS: We retrospectively analyzed outcomes in NDMM patients presenting with severe dialysis-requiring RI from 01/2010 to 12/2022.
RESULTS: Seventy patients were identified; all receiving novel agent-based induction (bortezomib-based 96%; lenalidomide-based 3%)-73% (n = 51) underwent ASCT. Thirty-three (48%) patients became dialysis independent; early achievement of VGPR in < 4.4 months from treatment initiation was identified as the only factor predicting renal recovery and dialysis withdrawal on univariate analysis (Hazard ratio [HR] of 4.172; p-value = 0.0014). At median follow-up of 39 months, the median overall survival (OS) of dialysis-requiring NDMM patients was 98.3 months with 2- and 5-year OS rates of 84% and 67%, respectively; 2- and 5-year progression-free survival (PFS) rates were 66.9% and 43.7%, respectively. On multivariable analysis, low LDH at diagnosis (HR: 1.003, p = 0.0092), undergoing ASCT (HR: 0.213; p-value = 0.0016), and dialysis independence (HR: 0.311; p-value = 0.0112) independently predicted improved OS.
CONCLUSIONS: Early VGPR and hemodialysis independence translated to improved survival, providing a benchmark for future comparison as anti-CD38 monoclonal antibodies enter first line therapy.

Keywords:  dialysis; newly diagnosed multiple myeloma; outcomes; renal impairment; renal recovery; survival

DOI:  https://doi.org/10.1111/ejh.70116
Ann Hematol. 2026 Jan 17. 105(1): 25

Paediatric blastic plasmacytoid dendritic cell neoplasm: a single-centre case series of 18 children and review of the literature.

Zhi-Xiao Zhang, Lin Zhang, Ai-Dong Lu, Le-Ping Zhang, Yue-Ping Jia, Fengrong Wang, Hui-Min Zeng.

  The incidence of paediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN) is extremely low, and little is known about the disease. This study aims to investigate its clinical course and optimal management. We retrospectively analysed the clinical manifestations, laboratory findings, treatment responses, and survival outcomes of 18 paediatric patients with BPDCN treated at our hospital. In this cohort, the male-to-female ratio was 2.6, and the median age of onset was 12 years. Bone marrow involvement was observed in 88.9% of patients (16/18), making it the most commonly affected site, followed by the skin (13/18) and lymph nodes (13/18). Central nervous system infiltration occurred in the youngest patient (Case 13), who experienced relapse after matched sibling donor haematopoietic stem cell transplantation (MSD-HSCT). Immunohistochemical and flow cytometry analyses revealed a distinct immunophenotype, with high expression of CD4 (94.4%), CD56 (100%), CD123 (100%), CD304 (100%), and HLA-DR (100%), and no expression of myeloperoxidase and CD19. In terms of the initial response, 14 patients received acute lymphoblastic leukaemia (ALL)-like regimens, all of whom achieved complete remission (CR) after induction chemotherapy. All 18 patients proceeded to HSCT post-chemotherapy, including 15 haploidentical and 3 MSD transplants. The 4-year overall survival (OS) and event-free survival (EFS) rates for the entire cohort were 94.4% ± 5.4% (95% CI, 83.8%-100.0%) and 87.7% ± 8.2% (95% CI, 71.6%-100.0%), respectively. Paediatric patients with BPDCN who receive allogeneic HSCT-particularly haploidentical HSCT-during CR following ALL-like induction chemotherapy appear to have favorable outcomes in this limited cohort.

Keywords:  Blastic plasmacytoid dendritic cell neoplasm; Children; Haematopoietic stem cell transplantation; Haploidentical

DOI:  https://doi.org/10.1007/s00277-026-06761-3
Ann Intern Med. 2026 Jan 13.

Iron Deficiency Anemia.

Kylee L Martens, Thomas G DeLoughery.

Iron deficiency anemia (IDA) is caused by iron deficiency, a common yet underrecognized clinical entity. Populations at greatest risk include children, menstruating and pregnant persons, and people of low socioeconomic status. Timely diagnosis and management of iron deficiency are key to preventing IDA and require thorough assessment of the underlying cause and appropriate iron repletion through either oral or parenteral therapy. Blood transfusion does not provide adequate elemental iron but is sometimes indicated along with iron therapy in patients with cardiovascular compromise, active bleeding, or severe anemia where more rapid correction is warranted. Alternative causes of anemia can be differentiated by red blood cell morphology and reticulocyte count and should be considered if anemia persists despite adequate repletion of iron stores.

DOI: https://doi.org/10.7326/ANNALS-25-04416
Br J Haematol. 2026 Jan 13.

Warm autoimmune haemolytic anaemia: Clinical considerations.

Irina Murakhovskaya, Karina Yazdanbakhsh.

  Warm autoimmune haemolytic anaemia (wAIHA) is an acquired autoimmune disorder caused by autoantibodies-primarily immunoglobulin G (IgG)-that bind to red blood cells and trigger haemolysis. It can be primary or secondary to associated conditions. This nutshell review summarizes pathophysiology, diagnostic workup, prognosis and treatment options.

Keywords:  haemolysis; haemolytic anaemia; warm autoimmune haemolytic anaemia

DOI:  https://doi.org/10.1111/bjh.70331
Blood Adv. 2026 Jan 27. 10(2): 492-493

Hydroxyurea pharmacokinetics, it is a small world after all.

Christina Caruso, Abena Appiah-Kubi.

DOI: https://doi.org/10.1182/bloodadvances.2025018221
Blood Adv. 2026 Jan 15. pii: bloodadvances.2025018345. [Epub ahead of print]

Exercise-Mobilized Lymphocytes Enhance the Function of Cytokine-Induced Memory-like NK-cells Against Myeloid Leukemia.

Helena Batatinha, Angella M Valenzuela, Dimitrios Filioglou, Phelipe Wilde, Geovana Leite, Timothy Mw Kistner, Forrest L Baker, Emmanuel Katsanis, Richard J Simpson.

Short-term activation of NK cells with IL-12/15/18 gives rise to cytokine-induced memory-like (CIML) NK cells after adoptive transfer, which exhibit enhanced anti-tumor activity, proliferation, and persistence. Clinical trials in high-risk leukemia have shown encouraging results, yet significant challenges remain, particularly the limited durability of cytotoxicity and the failure to achieve sustained remission. We recently demonstrated that acute exercise induces a 3-4-fold increase in circulating NK cells enriched for gene programs and surface proteins linked to anti-tumor activity. Here, we tested whether exercise-mobilized NK cells could improve the function of IL-12/15/18 activated NK-cells (aNK-cells) in vitro and CIML NK cells in vivo. Eighteen healthy donors performed 20 minutes of graded cycling up to 80% VO₂max, with blood collected at rest and during exercise. NK cells purified from rest and exercise (-X) were cultured overnight with IL-15 (NK or NK-X) or IL-12/15/18 (aNK or aNK-X). Endpoints included in vitro cytotoxicity and tumor control in leukemia-bearing xenogeneic mice. aNK-X exhibited stronger cytotoxicity against two myeloid leukemia cell lines than aNK from the same donors, accompanied by increased IFN-γ production, enhanced degranulation, and an enriched phenotype (higher NKG2A⁻/NKG2D⁺, CD57⁺, CD16⁺). Notably, NK-X displayed greater cytotoxic activity than NK and was comparable to aNK, though aNK-X outperformed both. In mice, CIML NK-X combined with exercise-mobilized donor lymphocyte infusion (DLI-X) prolonged engraftment, delayed tumor progression, and extended survival relative to CIML NK combined with standard DLI. These findings demonstrate that exercise-induced NK mobilization combined with cytokine pre-activation yields an adoptive cell therapy product with superior anti-leukemic activity. (NCT06643221).

DOI: https://doi.org/10.1182/bloodadvances.2025018345
Lancet. 2026 Jan 08. pii: S0140-6736(25)02164-6. [Epub ahead of print]

VEXAS syndrome: a comprehensive review of pathogenesis, clinical spectrum, and therapeutic strategies.

Emma M Groarke, Benjamin Turturice, Bhavisha A Patel, Kaitlin A Quinn, Alice Fike, Peter C Grayson.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a monogenic disease of adulthood characterised by treatment-refractory systemic inflammation and progressive bone marrow failure. VEXAS syndrome is caused by acquired mutations in the UBA1 gene that are restricted to haematopoietic cells. Men aged 50 years or older are particularly susceptible to VEXAS syndrome, with prevalence estimates of approximately one in 4000 men. Perturbation of UBA1, the master enzyme of cellular ubiquitination, promotes myeloid-driven inflammation that is difficult to control with medications other than glucocorticoids. Cytokine-directed therapies (ie, IL-6 and JAK inhibitors) might temporise symptoms and allow glucocorticoid reduction. Hypomethylating agents (ie, azacytidine) can induce clinical and molecular remission in some patients, but are associated with substantial toxicities. Haematopoietic cell transplant might be effective treatment in patients who are suitable candidates. The discovery of VEXAS syndrome highlights the potential role of somatic mutations in complex inflammatory diseases.

DOI: https://doi.org/10.1016/S0140-6736(25)02164-6
Health Promot Int. 2026 Jan 07. pii: daaf235. [Epub ahead of print]41(1):

Trust is a verb: how to reimagine confidence in health systems.

Tina D Purnat, Elisabeth Wilhelm, Gloria Lihemo, David Scales.

DOI: https://doi.org/10.1093/heapro/daaf235
J Immunother Cancer. 2026 Jan 14. pii: e013685. [Epub ahead of print]14(1):

Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.

Tao Dao, Guangyan Xiong, Jeremy Meyerberg, Zita Aretz, Akihiko Shiiya, Tatyana Korontsvit, Jingbao Liu, Ziyou Cui, Neel Panchwagh, Winson Cai, Chenyang Zhan, Hongbing Zhang, Cheng Liu, David A Scheinberg.

   BACKGROUND: Antigen loss and tumor heterogeneity present significant challenges for successful immunotherapies. T-cell receptor (TCR)-based therapies rely on the recognition of epitopes derived from intracellular tumor proteins presented by major histocompatibility complex class I molecules on cell surface. Solid tumor cells frequently lack immunoproteasomes, which are crucial for processing and presenting certain immunogenic epitopes. An effective strategy to mitigate the risk of antigen absence and tumor heterogeneity is to simultaneously target multiple tumor antigens, thereby providing critical rescue from disease relapse. Previously, we engineered a TCR mimic monoclonal antibody (TCRm) "ESK2", specific for Wilm's tumor 1 (WT1)-derived epitope RMFPNAPYL (RMF) in the context of HLA-A2, into a new chimeric antigen receptor T-cell format, antibody-TCR receptor (AbTCR)-chimeric signaling receptor (CSR). However, the RMF epitope is largely dependent on processing by the immunoproteasomes, which can be lost from leukemia cells and sometimes absent in solid tumor cells.
METHODS: To mitigate antigen loss, tumor heterogeneity and broaden the reach of AbTCR T cells, we combined ESK2 with a new TCRm for an immunoproteosome-independent epitope derived from WT1, VLDFAPPGA (VLD), in the context of HLA-A2 molecules, named ESK3. ESK2 and ESK3 were tandemly engineered into one AbTCR-CSR construct, simultaneously recognizing both the WT1 RMF and VLD epitopes. To add additional specificity and potency, a CSR in these cells was engineered with a single chain variable fragment (scFv) for either CD33 to treat leukemia or mesothelin to treat solid tumors. The specificity and efficacy of the AbTCR-CSRs were evaluated in both in vitro and in vivo.
RESULTS: In vitro studies demonstrated that the Tri-AbTCR-CSR (CD33 CSR) T cells showed the best killing activity against most acute myeloid leukemia cells. Similar levels of cytotoxicity were exhibited by ESK3 AbTCR-CSR (mesothelin CSR) against most solid tumor cell lines when compared with the Tri-AbTCR or a combination of ESK2 and ESK3 AbTCR-CSR. In animal therapy models, trispecific AbTCR-CSR T cells showed efficacy equivalent to single ESK2-AbTCR or ESK3-AbTCR-CSR T cells, against hematopoietic or solid tumor cells, further supporting the advantage of triple targeting strategy, overcoming epitope loss variants.
CONCLUSIONS: Trispecific T cells targeting immunoproteasome-dependent and independent epitopes of WT1 peptide/HLA-A2 complexes, plus a CSR recognizing a third tumor-associated antigen, present an effective and cost-efficient approach for overcoming tumor immune evasion.

Keywords:  Chimeric antigen receptor - CAR; Immunotherapy; Monoclonal antibody; T cell; T cell Receptor - TCR

DOI:  https://doi.org/10.1136/jitc-2025-013685
Int J Dermatol. 2026 Jan 17.

Bulky Auricular Folliculotropic Mycosis Fungoides: Dramatic Response and Rechallenge Efficacy With Extended Brentuximab Vedotin Therapy.

Serkan Yazici, Emel Bülbül Başkan, Fahir Özkalemkaş, Şaduman Balaban Adım.



Keywords:  CD30+ cutaneous lymphoma; brentuximab vedotin; folliculotropic mycosis fungoides

DOI:  https://doi.org/10.1111/ijd.70292
Bone. 2026 Jan 10. pii: S8756-3282(26)00015-3. [Epub ahead of print]205 117789

Models of myeloma bone disease: In vivo and in vitro approaches.

Jiaxian Wang, Sonja Zweegman, Richard W J Groen.

  This review focuses on experimental models developed to study myeloma bone disease (MBD), a major cause of morbidity in multiple myeloma (MM). Under physiological conditions, bone remodeling is regulated by osteoclasts (OCs) and osteoblasts (OBs); in MM, this balance is disrupted, resulting in enhanced bone resorption and suppressed bone formation. Myeloma cells alter the bone marrow (BM) microenvironment by increasing the RANKL/OPG ratio and secreting Wnt pathway inhibitors such as DKK-1 and sclerostin, thereby promoting osteoclastogenesis and inhibiting osteoblast differentiation. To dissect these mechanisms and evaluate therapeutic strategies, diverse preclinical systems have been developed. Syngeneic murine models, notably the 5T series, remain the most established for reproducing both osteolysis and impaired bone formation, though interspecies differences limit translational relevance. Humanized mouse systems and three-dimensional (3D) in vitro models increasingly address these constraints by incorporating human stromal and hematopoietic elements. Emerging induced pluripotent stem cell-derived bone marrow organoids (iBMOs) offer a fully human platform capable of modeling both osteoclast and osteoblast dynamics. While current iBMOs lack mineralized bone and mature vascular or immune components, advances in differentiation control and matrix engineering are expected to bridge these gaps, providing physiologically relevant and ethically sustainable models for studying MBD and testing therapeutic interventions.

Keywords:  3D in vitro models; Animal models; Myeloma bone disease; Osteoblastogenesis; Osteoclastogenesis

DOI:  https://doi.org/10.1016/j.bone.2026.117789
Rinsho Ketsueki. 2025 ;66(12): 1560-1565

[Extramedullary blast crisis limited to the lymph nodes in chronic myeloid leukemia with a T/myeloid mixed phenotype].

Toaki Maeda, Shunsuke Hatta, Keita Kanba, Tatsuya Watanabe, Daichi Kiba, Akihisa Kawajiri, Kyoko Inokura, Koichi Onodera, Yasushi Onishi, Noriko Fukuhara, Ryo Ichinohasama, Hideo Harigae.

  Blast crisis (BC) in chronic myelocytic leukemia (CML) typically presents with increased blasts in the bone marrow, showing either myeloid or B-lymphoid phenotypes. We report a rare case of CML-BC with a T/myeloid mixed phenotype localized to the lymph nodes. An 80-year-old woman presented with right axillary lymphadenopathy. PET-CT revealed multiple enlarged lymph nodes. Axillary node biopsy showed proliferation of medium-sized atypical lymphoid-like cells expressing both T-cell and myeloid markers. Both bone marrow and peripheral blood showed no abnormalities. The BCR::ABL1 translocation was detected in both bone marrow and lymph node tissue. Fluorescence in situ hybridization showed positive staining for BCR/ABL1 gene rearrangement. Based on these findings, blast crisis of CML with a T/myeloid mixed phenotype was diagnosed. Following dasatinib therapy, the enlarged nodes regressed. Despite the patient's advanced age, no significant adverse events have been observed during the course of treatment.

Keywords:  BCR::ABL1; Blast crisis; Chronic myelocytic leukemia

DOI:  https://doi.org/10.11406/rinketsu.66.1560