As the landscape of treatments for sickle cell disease (SCD) shifts, relatively little is known regarding the rates of medication prescription for SCD at a population level. This study was a cross-sectional annualized co...As the landscape of treatments for sickle cell disease (SCD) shifts, relatively little is known regarding the rates of medication prescription for SCD at a population level. This study was a cross-sectional annualized cohort analysis that used North Carolina Medicaid claims data from 2018 through 2022 to examine rates of prescription of FDA-approved medications for SCD and factors associated with their use. Adults with SCD were identified using a standard administrative data algorithm, and their data were aggregated to the person-year level. Annual prescription rates (≥ 1 claim) of hydroxyurea, L-glutamine, voxelotor, crizanlizumab, and opioid analgesics were calculated over time, and binomial mixed effects models examined associations between prescription and individual characteristics. Among 1733 individuals, the rate of hydroxyurea prescription ranged from 24.2%-26.7%. Rates for L-glutamine, voxelotor, and crizanlizumab were less than 6.0% each year. The rate of opioid prescription ranged from 51.4%-53.9%. Seeing a hematologist was consistently associated with higher odds of receiving SCD-specific medications. Age was associated with decreased prescription of hydroxyurea, L-glutamine, and opioids, but increased prescription of voxelotor. Males had higher odds of receiving hydroxyurea. Although use of FDA-approved medications for SCD was low, improved access to hematologists may increase medication utilization.
BACKGROUND: Musculoskeletal (MSK) symptoms are a frequent but diagnostically ambiguous presentation in children with malignancies such as leukemia and neuroblastoma. These symptoms may precede hematologic abnormalities,...BACKGROUND: Musculoskeletal (MSK) symptoms are a frequent but diagnostically ambiguous presentation in children with malignancies such as leukemia and neuroblastoma. These symptoms may precede hematologic abnormalities, complicating early diagnosis and increasing the risk of misclassification. Inappropriate treatments, such as corticosteroids, may further obscure disease features. OBJECTIVE: To identify clinical and laboratory indicators of leukemia and neuroblastoma at initial evaluation in children presenting with MSK symptoms and to develop a simple preliminary triage tool (TRIM). METHODS: In this retrospective study, 333 of 457 children (≤ 18 years) with MSK symptoms (2020-2024) had ≥ 6 months follow-up and were included. Clinical and laboratory data from the first encounter were analyzed. Predictors were identified using Firth logistic regression and incorporated into weighted subscores for leukemia (TRIM-L) and neuroblastoma (TRIM-N). Performance was assessed using AUC and predictive metrics with bootstrap internal validation. RESULTS: Malignancy was diagnosed in 9/333 patients (2.7%; leukemia 1.5%, neuroblastoma 1.2%). Independent indicators of leukemia were splenomegaly, hemoglobin < 8.5 g/dL, and platelet count < 150 000/μL. Independent indicators of neuroblastoma were lymphadenopathy, weight loss, and LDH > 400 U/L. Discrimination was high (AUC: leukemia 0.996; neuroblastoma 0.963). Using a cutoff ≥ 2, TRIM-L achieved 100% sensitivity, 97% specificity, and 100% NPV; TRIM-N achieved 75% sensitivity, 97.3% specificity, and 99.7% NPV. CONCLUSIONS: Splenomegaly, cytopenias, lymphadenopathy, elevated LDH, and weight loss were key early indicators of malignancy in children presenting with MSK symptoms. The internally derived TRIM score showed excellent negative predictive value and may assist early triage; however, external validation is required before clinical application.
Martino EA, Caserta S, Skafi M
… +10 more, Alvaro ME, Bruzzese A, Amodio N, Lucia E, Olivito V, Labanca C, Mendicino F, Vigna E, Morabito F, Gentile M
Eur J Haematol
· 2026 Apr · PMID 41453809
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Follicular lymphoma (FL), traditionally considered an indolent yet incurable malignancy, is experiencing a substantial evolution in its therapeutic landscape with the emergence of chemo-free treatment strategies. These n...Follicular lymphoma (FL), traditionally considered an indolent yet incurable malignancy, is experiencing a substantial evolution in its therapeutic landscape with the emergence of chemo-free treatment strategies. These novel approaches challenge conventional chemotherapy-based paradigms and offer promising alternatives for both newly diagnosed and relapsed/refractory (RR) FL patients. Among these innovations, bispecific antibodies (BsAbs) have demonstrated compelling efficacy while providing practical advantages, including outpatient administration and generally manageable safety profiles. Chimeric antigen receptor (CAR) T-cell therapies have further expanded the therapeutic armamentarium, achieving unprecedented response rates in heavily pretreated and high-risk populations, although their implementation remains limited by logistical complexity and high associated costs. Additional targeted agents-such as Enhancer of zeste homolog 2 (EZH2) inhibitors, lenalidomide, and Bruton tyrosine kinase (BTK) inhibitors-also contribute meaningfully to chemo-free treatment options, particularly within combination regimens that may enhance clinical benefit. Despite these advances, several challenges persist. Early disease progression (POD24) remains one of the most powerful prognostic determinants in FL. The FLIPI-C model, incorporating machine-learning-derived risk stratification, has shown promise in identifying high-risk patients who may benefit most from innovative approaches. Introducing chemo-free therapies earlier in the treatment algorithm may improve outcomes for these patients while mitigating the long-term toxicities associated with conventional chemotherapy. Ongoing validation through prospective clinical trials and real-world evidence will be essential to define the optimal integration of these therapies. Overall, this evolving paradigm highlights the urgent need for continued innovation, multidisciplinary collaboration, and equitable access to ensure that the full potential of chemo-free strategies can be realized for patients with this complex disease.
Caserta S, Martino EA, Skafi M
… +10 more, Alvaro ME, Bruzzese A, Amodio N, Lucia E, Olivito V, Labanca C, Mendicino F, Vigna E, Morabito F, Gentile M
Eur J Haematol
· 2026 Apr · PMID 41449642
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PD-1 inhibitors have reshaped the treatment landscape of classical Hodgkin lymphoma, yet a substantial proportion of patients exhibit primary or acquired resistance driven by tumor-intrinsic alterations, immunosuppressiv...PD-1 inhibitors have reshaped the treatment landscape of classical Hodgkin lymphoma, yet a substantial proportion of patients exhibit primary or acquired resistance driven by tumor-intrinsic alterations, immunosuppressive microenvironmental signals, metabolic constraints, and EBV-mediated modulation. This review summarizes key mechanisms underlying PD-1 resistance and highlights emerging biomarkers-including early F-FDG PET response, circulating tumor DNA kinetics, molecular subtyping, and spatial immune profiling-that enable early identification of nonresponders and support precision immunotherapy. Novel therapeutic strategies such as macrophage-targeted agents, metabolic modulators, bispecific antibodies, low-dose PD-1 regimens, and CD30-directed CAR-T cells show promise in overcoming resistance, particularly when integrated into adaptive, biomarker-guided treatment algorithms. Early incorporation of PET and ctDNA monitoring may inform timely treatment adaptation, while combination approaches addressing macrophage-driven suppression or redundant immune checkpoints should be considered in biologically high-risk patients. Overall, a deeper mechanistic understanding coupled with biomarker-driven stratification is essential to optimize PD-1-based therapy and improve long-term outcomes in cHL.
Ho TN, Willard P, Murray GF
… +4 more, Liu L, Wages N, Lee H, Maher KR
Eur J Haematol
· 2026 Apr · PMID 41435898
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Therapeutic options for newly diagnosed (ND) acute myeloid leukemia (AML) have increased in recent years, leading to a shift in the treatment paradigm from conventional, intensive chemotherapy toward targeted and less in...Therapeutic options for newly diagnosed (ND) acute myeloid leukemia (AML) have increased in recent years, leading to a shift in the treatment paradigm from conventional, intensive chemotherapy toward targeted and less intensive therapy. Since 2017, there has been a surge in FDA approvals for novel therapies, including small molecule inhibitors and new combinations of chemotherapy and targeted drugs. It is unclear what effect these changes have had on overall survival in the real-world clinical setting over time. We retrospectively analyzed 501 patients with ND AML treated at an urban academic cancer center from 2015 to 2022 with respect to survival rates and treatment regimen utilization trends over time, in the context of AML risk category and whether allogeneic stem cell transplantation (HSCT) occurred. Among European LeukemiaNet 2022 intermediate risk ND AML patients who did not undergo HSCT, overall survival and relapse-free survival improved significantly in the early versus later cohort (2015-2018 vs. 2019-2022, respectively). These gains were not observed in the adverse-risk subgroup, where outcomes remain unchanged. First-line use of hypomethylating agent-based therapies increased seven-fold, while reliance on chemotherapy alone decreased by half. These findings highlight a meaningful shift in treatment patterns associated with improved outcomes overall, but an ongoing lack of progress in the highest-risk subgroups.
Endothelial cells play a complex role in lymphoma by becoming genetically abnormal alongside tumor cells, forming blood vessels that fuel lymphoma growth and invasiveness, and contributing to the establishment of an immu...Endothelial cells play a complex role in lymphoma by becoming genetically abnormal alongside tumor cells, forming blood vessels that fuel lymphoma growth and invasiveness, and contributing to the establishment of an immunosuppressive tumor microenvironment. Because of their significant role in lymphoma growth and immune evasion, endothelial cells and the processes that regulate them are being explored as attractive targets for new anti-angiogenic therapies and immunotherapies to overcome the limitations of anti-angiogenic therapy in lymphoma treatment.
Frey SM, Halberstadt P, Alashkar F
… +3 more, Lenz V, Reinhardt HC, Röth A
Eur J Haematol
· 2026 Apr · PMID 41424032
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Cold agglutinin disease (CAD) is a low-grade lymphoproliferative disorder accounting for 15%-30% of patients suffering from autoimmune hemolytic anemias. The clonal B cells produce autoantibodies primarily of the IgM-κ c...Cold agglutinin disease (CAD) is a low-grade lymphoproliferative disorder accounting for 15%-30% of patients suffering from autoimmune hemolytic anemias. The clonal B cells produce autoantibodies primarily of the IgM-κ class that cause agglutination of red blood cells (RBCs) at temperatures ≤ 37°C and activate the classical complement pathway with subsequent RBC destruction. Before the approval of the monoclonal antibody sutimlimab, treatment options were limited. Sutimlimab inhibits the classical complement pathway at C1s while sparing the lectin and alternative complement pathways. Efficacy, safety and tolerability of sutimlimab have been established in the multicenter CARDINAL and CADENZA trials. In the present investigation, 10 patients on sutimlimab were followed up to 96 weeks in the Managed Access Program (MAP) in Essen. Eight of these patients had previously participated in the multicenter trials and were restarted on sutimlimab after a median washout period of 12.6 weeks. In addition, two sutimlimab-naive patients were included. Hemoglobin concentration increased in all patients (median hemoglobin concentration before therapy 9.8 vs. 12.5 g/dL at the end of the study). Bilirubin levels normalized already after 2 weeks in all patients. Reticulocyte count declined in nine, haptoglobin and hemopexin concentrations normalized in six and 10 patients, respectively. In conclusion, the present investigation with primary CAD patients in a single center demonstrates long-term normalization of laboratory parameters, abrogation of specific clinical symptoms and absence of drug-related side effects with sutimlimab.
BACKGROUND: Immunomodulatory agents (IMiDs) are a cornerstone in the successful management of multiple myeloma (MM). However, acquired IMiD resistance leading to disease relapses remains a major barrier. Hydrogen peroxid...BACKGROUND: Immunomodulatory agents (IMiDs) are a cornerstone in the successful management of multiple myeloma (MM). However, acquired IMiD resistance leading to disease relapses remains a major barrier. Hydrogen peroxide generation and oxidative stress are key mediators that determine IMiD's effectiveness in MM. Iron plays a key role in the generation of oxidative stress; therefore, cellular iron levels are tightly governed. FTH1 is the major iron storage protein that tightly regulates cellular iron availability. Hence, the present study is targeted to investigate the role of FTH1 in MM and IMiD resistance. METHODS: IMiD-sensitive and IMiD-resistant MM cells were analyzed for expression of iron-metabolism genes. CRISPR-cas9-mediated knockout of FTH1 was performed and the after-effects were assessed through multiple experiments. RESULTS: Initial analysis showed a positive correlation between FTH1 expression and IMiD resistance in MM cells. FTH1-KO reduced IMiD sensitivity in the KMS11 cell line but had no effect on the RPMI8226 cell line. RNA-seq data showed downregulation of ER-stress and calcium signaling genes after FTH1-KO. Further, KMS11-FTH1KO cells exhibited lower intracellular ROS, labile-iron, and mitochondrial superoxide levels along with increased CD63, suggesting activation of L-ferritin secretory pathways. CONCLUSION: Data reveals a link between FTH1, labile iron, ROS, and IMiD resistance in MM cells.
Solid tumors can be associated with a variety of hematologic manifestations, including paraneoplastic syndromes, coagulopathy, and electrolyte derangements. Evaluation and management require a multidisciplinary approach...Solid tumors can be associated with a variety of hematologic manifestations, including paraneoplastic syndromes, coagulopathy, and electrolyte derangements. Evaluation and management require a multidisciplinary approach and a clear understanding of the role and timing of surgical resection, as this can provide definitive treatment. This review summarizes current literature and offers a practical approach to stabilization and surgical-focused management of solid tumors presenting with hematologic manifestations. The scope focuses on hematologic or metabolic paraneoplastic presentations with direct relevance to surgical timing and perioperative care; endocrine hormone excess syndromes (e.g., ectopic ACTH, SIADH) are excluded. For mechanism-linked hematologic or metabolic manifestations, early surgical consultation is recommended. Bridge therapies enable safe anesthesia and resection, while durable correction generally requires tumor control. A standardized, age-focused perioperative approach is integral for optimal patient outcomes.
Kasmi D, Bisegna ML, Carmosino I
… +10 more, Scalzulli E, Costa A, Cenfra N, Mecarocci S, Capria S, Minotti C, Martelli M, Cartoni C, Pulsoni A, Breccia M
OBJECTIVES: Azacitidine (AZA) combined with venetoclax (VEN) as an outpatient treatment of unfit patients with acute myeloid leukemia (AML) has been infrequently investigated. METHODS: We report on 65 elderly AML patient...OBJECTIVES: Azacitidine (AZA) combined with venetoclax (VEN) as an outpatient treatment of unfit patients with acute myeloid leukemia (AML) has been infrequently investigated. METHODS: We report on 65 elderly AML patients: 35 patients received AZA + VEN as first-line and 30 after progression on prior treatment with AZA (R/R group). Thirty-eight patients were treated as outpatients, while 27 were hospitalized. The overall survival (OS) and event-free survival (EFS) were calculated, and predictive factors were assessed using Cox regression models. RESULTS: Inpatients were slightly younger, with a median age of 72 versus 74 years in outpatients (p = 0.015). Median WBC was higher in inpatients (median 7.3 × 10/L vs. 2.9 × 10/L, p = 0.020). Median marrow blast count was 43% in inpatients versus 25.5% in outpatients (p = 0.042). Treatment setting emerged as a key predictive factor for infection development during Cycle 1 in both univariate (p = 0.016) and multivariate analysis (p = 0.043), in the overall cohort. Inpatients had a significantly higher infection rate (81.4%) versus outpatients (44.7%, p = 0.004). In R/R group, 1-year EFS was 68% for outpatients versus 38% for inpatients (p = 0.009). One-year OS was 77% in outpatients versus 38% in inpatients (p = 0.052). CONCLUSIONS: In most instances, outpatient administration of Cycle 1 of AZA + VEN should be preferred as a beneficial option.
Queffeulou C, Bellal M, Goursaud S
… +2 more, Chantepie S, du Cheyron D
Eur J Haematol
· 2026 Apr · PMID 41414818
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BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome. It is a severe condition with a challenging diagnosis in the intensive care unit (ICU), for which current recommendations rely on...BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome. It is a severe condition with a challenging diagnosis in the intensive care unit (ICU), for which current recommendations rely on fulfilling five of eight HLH-2004 criteria. METHODS: Our single-center retrospective cohort included adults admitted to the ICU in whom HLH was diagnosed, suspected, or excluded. The primary outcome was the prevalence of HLH in the ICU according to the HLH 2004 criteria. Additional factors analyzed included prognosis and diagnosis (determined by clinician judgment, HLH 2004 criteria with a four variable threshold and HScore). RESULTS: Among 123 included patients, 30 met HLH-2004 criteria, corresponding to a prevalence of 0.42% of ICU admissions, likely underestimated. Their 28-day mortality rate was 46.7%; their 1-year mortality rate was 75%. In the entire cohort, absence of infection as a trigger and higher SAPS II scores were independently associated with 28-day mortality in multivariate analysis. Diagnostic concordance was 69.1% with the HScore, 61.8% with clinician judgment, and 71.5% with the four-variable HLH-2004 threshold, yielding an overall agreement of 46.3%. CONCLUSION: Our study describes a population of adults suspected of HLH in the ICU. Improved diagnostic strategies are needed to facilitate timely recognition and optimize patient outcomes.
Buvelot H, Baleydier F, Pittet L
… +1 more, Blanchard-Rohner G
Eur J Haematol
· 2026 Apr · PMID 41408960
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Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used to treat malignant and non-malignant diseases. Following allogeneic HSCT, patients are particularly vulnerable to vaccine-preventable disease...Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used to treat malignant and non-malignant diseases. Following allogeneic HSCT, patients are particularly vulnerable to vaccine-preventable diseases (VPD) because conditioning depletes immune cells, including memory cells. Revaccination is therefore essential, but multiple factors, such as conditioning regimen, stem cell source, HLA compatibility, graft-versus-host-disease (GVHD), and age, affect immune reconstitution and vaccine response. Current guidelines recommend uniform vaccination schedule for all allogeneic HSCT patients, despite this heterogeneity. In this review, we discuss how these factors influence immune reconstitution and vaccine response, and highlights the need for a more individualized approach. Based on current evidence, we propose that vaccine timing, particularly for inactivated vaccines, could benefit from adjustment according to immune recovery markers, such as lymphocyte counts and presence of GVHD, rather than relying on fixed post-HSCT timepoints. We also discuss emerging immunotherapies, including CAR-T cells and bispecific antibodies, which can induce similarly prolonged immunosuppression and may benefit from personalized vaccination strategies. Further studies in pediatric populations are needed to define immunological threshold that would enable safer and more effective personalized vaccination schedules.
OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a severe hyperinflammatory syndrome requiring rapid recognition and treatment. Despite the expanding availability of biologic and cytokine-directed thera...OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a severe hyperinflammatory syndrome requiring rapid recognition and treatment. Despite the expanding availability of biologic and cytokine-directed therapies, etoposide-based immunochemotherapy remains the primary treatment in many pediatric centers. This study evaluated the efficacy, response kinetics, and clinical outcomes of etoposide-based therapy in children with sHLH. METHODS: We retrospectively analyzed 32 pediatric patients diagnosed with sHLH between 2018 and 2023 at a tertiary center. Diagnosis was based on HLH-2004 criteria; primary HLH was excluded through genetic testing when available. All patients received dexamethasone and etoposide, with cyclosporine A initiated after Week 1. Trigger-directed therapies included rituximab for EBV-HLH and anakinra or tocilizumab in selected hyperinflammatory states. Laboratory dynamics (ferritin, fibrinogen, platelets, and absolute neutrophil count), clinical responses, relapse, hematopoietic stem cell transplantation (HSCT), and overall survival (OS) were assessed. RESULTS: The median age was 38 months; 62.5% were male. Triggers included EBV (34%), other viral infections (19%), rheumatologic disease/MAS (16%), bacterial infection (13%), and malignancy (9%). By Week 4, ferritin decreased from 6480 to 1240 ng/mL and fibrinogen increased from 122 to 286 mg/dL (p < 0.001). Fever resolved in 90% by Week 2, and 81% achieved complete laboratory response. During a median follow-up of 18 months, relapse occurred in 18.8% and HSCT was required in 15.6% of patients. Overall survival was 91% at 1 year and 86% at 2 years. Adverse events were consistent with expected etoposide-related toxicities. CONCLUSION: Etoposide-based immunochemotherapy provided rapid disease control and favorable survival in pediatric sHLH. These findings support the continued relevance of etoposide while underscoring the need for risk-adapted approaches integrating trigger-directed therapy, cytokine inhibitors, and timely HSCT in selected patients.
BACKGROUND: Children diagnosed with leukemia require prolonged central venous access for chemotherapy, transfusions, and supportive care. Due to their immunocompromised status, coagulopathies, and intensive treatment pro...BACKGROUND: Children diagnosed with leukemia require prolonged central venous access for chemotherapy, transfusions, and supportive care. Due to their immunocompromised status, coagulopathies, and intensive treatment protocols, they may be at increased risk for central venous access device (CVAD)-related complications, including infection, thrombosis, and mechanical failure. This study aimed to quantify the incidence and characterize the nature of CVAD-associated complications in this high-risk pediatric population. METHODS: A systematic review (1970-2025) was conducted using PRISMA guidelines, including studies describing CVAD-associated complications in children (≤ 18 years old) undergoing treatment for leukemia. The Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool was used to assess the studies' quality. Meta-analysis and proportional meta-analysis for non-comparative studies (Freeman-Tukey transformation) using the random-effects model were conducted. RESULTS: Six databases were searched identifying 1126 articles: 1102 were excluded and 24 studies with 13 879 CVADs were included. CVAD-associated complications identified included: device failure 18.5% (95% CI 10.8-27.8), central line-associated bloodstream infection (CLABSI) 31.3% (95% CI 23.6-39.6), local infection 5.4% (95% CI 2.5-9.3), CVAD-associated venous thromboembolism (VTE) 5.2% (95% CI 2.9-8.3), dislodgement/migration 2.4% (95% CI 1.5-3.5), breakage/rupture 3% (95% CI 1.9-4.3), occlusion 5.3% (95% CI 1.5-11.2), wound dehiscence 4.4% (95% CI 2.2-7.3), and accidental removal 4.9% (95% CI 2.0-9.0). Tunneled central venous access devices (TCVADs) were associated with a higher proportion of complications when compared to totally implantable venous access devices (TIVADs). CONCLUSION: Device failure and CLABSI are the CVAD-associated complications with the highest incidence rates. Comparing CVAD subtypes, TCVADs may have a higher complication risk than TIVADs. Further large prospective studies with long-term follow-up are needed to investigate these findings and determine their impact on patient morbidity and mortality.
Al-Omari R, Nampoothiri RV, Sakhdari A
… +10 more, Atenafu EG, Chiarello C, Kim DD, Law A, Pasic I, Novitzky-Basso I, Viswabandya A, Michelis FV, Mattsson J, Kumar R
The utilization of eltrombopag (EPAG) in the management of post allogenic hematopoietic cell transplant (HCT) cytopenia has exhibited promising outcomes. Isolated thrombocytopenia and poor graft function (PGF) are factor...The utilization of eltrombopag (EPAG) in the management of post allogenic hematopoietic cell transplant (HCT) cytopenia has exhibited promising outcomes. Isolated thrombocytopenia and poor graft function (PGF) are factors that adversely influence transplant outcomes and patient well-being. This retrospective study aims to assess EPAG efficacy in this context as a primary outcome and evaluate early EPAG tapering post complete response (CR) for cost efficiency and response durability as a secondary outcome. We analyzed 39 patients who underwent allogeneic HCT; EPAG was administered to 89.7% of patients for PGF and 10.3% for isolated thrombocytopenia. The overall response rate (ORR) after 4 weeks of EPAG treatment was 71.8%, with 48.7% achieving a complete response (CR). Early tapering of EPAG post-CR was explored for cost benefit among responders. Early tapering was defined as the start of tapering after 4 weeks of achieving CR and was found to be associated with significant response durability with a trend towards cost effectiveness. Eltrombopag response was independent of megakaryocyte number or density prior to drug initiation. The study suggests EPAG as a safe treatment for PGF and isolated thrombocytopenia post-allogeneic HCT and proposes early drug tapering as a potentially cost-beneficial approach.
Cunningham I, Fisher RA, Yang J
… +2 more, Guo Y, Bommhardt U
Eur J Haematol
· 2026 Mar · PMID 41369097
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Since 2004, patients receiving imatinib with relapse in non-marrow sites were given dasatinib to preserve control of leukemic marrow. Remissions in CNS and other organs began to be reported and are continuously observed...Since 2004, patients receiving imatinib with relapse in non-marrow sites were given dasatinib to preserve control of leukemic marrow. Remissions in CNS and other organs began to be reported and are continuously observed to present. With resistance to one BCR::ABL1 tyrosine kinase inhibitor and sensitivity to a dual BCR::ABL1/SRC inhibitor recognized, we undertook a retrospective observational study of all reported patients with EML given dasatinib ± routine therapies used over 50 years. We elicited remission durations from authors. One hundred and sixty-three patients (150 Ph'+, 13 Ph'- negative leukemias) received dasatinib ± conventional EML treatments. All but six cases reported disappearance of EML involvement, documented by MRI, CSF, PET/CT in 10, and autopsy in 2. To date, 36 EML remissions have lasted 2+-11+ years (15 > 4 years). Thirty-four of the responding patients had post-dasatinib transplants and 3 CAR-T therapy. The tyrosine kinase inhibitor overexpressed in our prior RNAseq studies of EML tissue was LCK, a SRC kinase target of dasatinib known to be present in CNS, nerves, and some cancers. We present published data to support LCK as one possible tissue target in EML. As there has never been any durably effective treatment for EML, these observations merit prospective trials to validate the observed success of dasatinib and determine the role of additional therapies including cellular therapies. Dasatinib is a potentially practice-changing targeted therapy for EML. Finding and eradicating EML could increase the possibility of lengthy disease-free survival.
Alsouqi A, Huang Y, Christian B
… +14 more, Reneau J, Bhat SA, Brammer J, Sawalha Y, Baiocchi RA, Grever M, Rogers KA, Reeser J, Smith A, Samorodnitsky E, Roychowdhury S, Maddocks K, Woyach JA, Bond D
Identifying patients eligible for front-line clinical trials with diffuse large B-cell lymphoma (DLBCL) has been challenging, primarily due to increasingly stringent inclusion criteria and the limitations of the Internat...Identifying patients eligible for front-line clinical trials with diffuse large B-cell lymphoma (DLBCL) has been challenging, primarily due to increasingly stringent inclusion criteria and the limitations of the International Prognostic Indices in identifying patients who are unlikely to achieve long-term remission after standard treatment. We aimed to assess the impact of using improved eligibility criteria established through a US-based Delphi-method survey to identify real-world DLBCL patients eligible for clinical trials. Additionally, we developed a predictive model to assess the individual risk of trial-eligible patients with an online calculator. Of 5341 potential trial candidates identified from the Danish Lymphoma Registry, 4063 patients (76.1%) were trial-eligible if the recommended eligibility criteria were applied. Among excluded patients, 7.9% would be excluded due to inadequate organ function. To develop a predictive model for progression-free survival, we randomly divided the population into a training and a validation cohort (3:1 ratio). Then, the Delphi Trial Prognostic Index (DTPI) was developed based on eight clinical and laboratory variables, demonstrating superior performance compared to the International Prognostic Indices. Our prediction model, which incorporates less restrictive eligibility criteria and utilizes an online calculator, was designed to more accurately predict outcomes for potential candidates eligible for first-line clinical trials.
Dülberg J, Sanchez C, Burckhardt MA
… +18 more, Alacán Friedrich L, Salow V, Radauer-Plank A, Borgmann-Staudt A, Cario H, Diepold M, Drexler B, Infanti L, Kroiss S, Dietliker N, Merki R, Njue L, Oevermann L, Rovó A, Scheinemann K, Schneider M, Balcerek M, Diesch-Furlanetto T
Eur J Haematol
· 2026 Mar · PMID 41354636
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OBJECTIVES: Although Advancements in the Treatment of Hemoglobinopathies have Considerably Increased Life Expectancy, Hormonal and Pubertal Development Have Been Continuously Affected by Complications From Transfusion-Re...OBJECTIVES: Although Advancements in the Treatment of Hemoglobinopathies have Considerably Increased Life Expectancy, Hormonal and Pubertal Development Have Been Continuously Affected by Complications From Transfusion-Related Iron Overload and Cytotoxic Therapies. This Study Investigated the Association Between Serum Ferritin Levels and Pubertal Progression in Patients With Thalassemia and Sickle Cell Disease (SCD). METHODS: Data Collected From 10 Hospitals in Austria, Germany, and Switzerland From 2012 to 2020 Were Retrospectively Analyzed. We Enrolled 140 Individuals (Median Age: 16.5 Years) With Thalassemia or SCD. RESULTS: Overall, Delayed Puberty Was Observed in 14.7% (6.7% Females; 21.1% Males) and 13.2% of Patients With Thalassemia and SCD (6.9% Females; 20.8% Males), respectively. Gonadal Insufficiency Was Found in 13.3% and 8.6% of Females With Thalassemia and SCD, Respectively. Abnormal Growth Trajectories Were Observed in 32.5% (28.5% Females; 36.8% Males) and 18.7% of Patients With Thalassemia and SCD (13.3% Females; 23.5% Males), respectively. A Statistically Significant Association Was Found Between Elevated Ferritin Levels and Growth Delays in Patients With Thalassemia. Notably, Tanner Staging Data Were Missing in 80.7% of the Medical Records. CONCLUSIONS: Our Results Indicated the Need for Comprehensive Pubertal Screening and Underscored the Importance of Robust Endocrine Follow-Up Care in Individuals With Hemoglobinopathies.
INTRODUCTION: Prognostic models in Waldenström's macroglobulinemia (WM) are typically static, baseline tools applied before treatment initiation and do not account for dynamic post-treatment factors. We evaluated time to...INTRODUCTION: Prognostic models in Waldenström's macroglobulinemia (WM) are typically static, baseline tools applied before treatment initiation and do not account for dynamic post-treatment factors. We evaluated time to next treatment within 24 months (TTNT24), as a prognostic marker in symptomatic patients, and time to lymphoma treatment within 24 months (TTLT24) in initially observed asymptomatic patients. METHODS: In this observational cohort study, patients diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in Region Zealand from 2000 to 2023 were identified using Danish national registries and health records. TTNT24 was defined as initiation of second-line treatment within 24 months of first-line therapy. TTLT24 was defined as lymphoma-directed treatment initiated within 24 months of diagnosis in initially asymptomatic patients. RESULTS: Among 526 LPL/WM patients, 218 symptomatic patients were evaluated for TTNT24 with 33 (15%) patients receiving second-line treatment within 24 months. TTNT24-positive patients demonstrated inferior overall and lymphoma-related survival compared to TTNT24-negative patients. TTNT24 remained significant in multivariate analysis. Among 310 asymptomatic patients, TTLT24 was significantly associated only with lymphoma-related survival. CONCLUSION: TTNT24 and TTLT24 may serve as dynamic prognostic markers in real-world LPL/WM populations. Their relevance in the era of targeted therapies warrants further investigation.