European Journal Of Haematology[JOURNAL]
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200 papers
Efficacy of CD38-Targeted Therapy in Severe, Multi-Agent Refractory Immune Thrombocytopenia: A Case Series.
Patel PS, Farrugia S, Nunnelee J … +4 more , Mina S, Godby RC, Go R, Rajkumar SV
Eur J Haematol · 2026 Jul · PMID 41923527 · Publisher ↗
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antibody-mediated platelet destruction, often driven by long-lived plasma cells (LLPCs) resistant to conventional therapies. While most pa...
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antibody-mediated platelet destruction, often driven by long-lived plasma cells (LLPCs) resistant to conventional therapies. While most patients respond to corticosteroids and intravenous immunoglobulin (IVIG), a subset develops life-threatening refractory disease. In this case series, we describe three patients aged 39, 85, and 58 with life-threatening, multi-agent refractory ITP and platelet nadirs < 2 × 10/L who failed corticosteroids, IVIG, and thrombopoietin receptor agonists (TPO-RAs). Following salvage therapy with daratumumab, a monoclonal antibody targeting CD38, all three patients achieved rapid hematologic recovery, with platelet count normalization within 1 week. This accelerated response allowed for urgent clinical stabilization, including safe anticoagulation and surgical intervention. The efficacy of daratumumab likely stems from a dual mechanism: the depletion of CD38+ LLPCs and the immediate modulation of Fc-receptor-mediated platelet clearance. These observations suggest that CD38-targeted therapy can bypass traditional treatment resistance to achieve near-immediate remission in high-complexity, high-risk clinical settings. While these results are compelling, prospective clinical trials are warranted to define the long-term safety, durability, and optimal dosing of anti-CD38 therapies in refractory ITP populations.
Specialist Palliative Care and the Use of Healthcare Services Among Patients With Multiple Myeloma: A Nationwide Cohort Study.
Holopainen A, Lehto HR, Kuittinen T … +5 more , Nuutinen M, Tyynelä-Korhonen K, Lamminmäki A, Saarto T, Carpén T
Eur J Haematol · 2026 Jul · PMID 41923492 · Publisher ↗
OBJECTIVES: To investigate the access to specialist palliative care (SPC) and its impact on healthcare utilization at the end of life in patients with multiple myeloma (MM). METHODS: This retrospective cohort study exami...
OBJECTIVES: To investigate the access to specialist palliative care (SPC) and its impact on healthcare utilization at the end of life in patients with multiple myeloma (MM). METHODS: This retrospective cohort study examined all Finnish patients who died of MM in 2019. Data were collected from national health databases. Patients were categorized by whether they had contact with SPC or not. RESULTS: We identified 278 patients (median age at death 77.5 years, 44.2% male), of whom 23.4% had SPC contact a median of 38 days before death. During the last 6 months of life, 92.4% of all patients had contact with the emergency department, 83.5% were hospitalized in secondary care, and 65.5% were hospitalized in primary care hospitals. Patients with SPC contact had fewer emergency department visits (50.8% vs. 65.3%, p = 0.041) and hospitalizations in secondary care (41.5% vs. 62.0%, p = 0.004) in the last month of life and fewer hospital deaths (69.2% vs. 84.0%, p = 0.012). CONCLUSIONS: Despite high healthcare service utilization at the end of life, access to SPC was often limited and late. Contact with SPC reduced acute healthcare utilization at the end of life, indicating better end-of-life care.
Venetoclax-Integrated Conditioning Strategies Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Myeloid Neoplasms: A Scoping Review of Emerging Evidence.
Abdulgayoom M, Gulied A, Alshurafa A … +3 more , Mohamed SF, Yassin MA, Fadul A
Eur J Haematol · 2026 Jul · PMID 41917774 · Publisher ↗
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative therapy for many patients with high-risk myeloid neoplasms, yet relapse and transplant-related toxicity continue to lim...
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative therapy for many patients with high-risk myeloid neoplasms, yet relapse and transplant-related toxicity continue to limit durable benefit. Venetoclax (VEN), a selective BCL-2 inhibitor, provides a biologically compelling strategy for conditioning augmentation through chemotherapy sensitization and potential lowering of host immune resistance to engraftment. We performed a hybrid scoping review and evidence-mapping analysis to summarize published clinical experience and the active investigational landscape of VEN-containing conditioning or sequential regimens prior to allo-HSCT. Eighteen studies (20 reports) met the inclusion criteria, including nine published cohorts comprising 238 patients and 11 ongoing clinical trials. Reported platforms were heterogeneous, spanning reduced-intensity, myeloablative, and sequential approaches. Engraftment and graft-versus-host disease outcomes were generally comparable to expected benchmarks, although available data remain preliminary and non-randomized, underscoring that the primary aim of this scoping review is to map existing evidence and ongoing trials rather than to inform clinical practice or guideline recommendations.
Long-Term Clinical and Molecular Dynamics in Hypoplastic Myelodysplastic Neoplasia Treated With Immunosuppressive Therapy.
Treiber H, Ganster C, Shirneshan K … +6 more , Rittscher K, Brzuszkiewicz E, Hasenkamp J, Jung W, Wulf G, Haase D
Eur J Haematol · 2026 Jul · PMID 41910048 · Publisher ↗
Myelodysplastic neoplasia (MDS) comprises heterogeneous clonal hematologic disorders characterized by peripheral cytopenia, bone marrow dysplasia, and a risk of leukemic transformation. A hypoplastic variant (MDS-h) shar...
Myelodysplastic neoplasia (MDS) comprises heterogeneous clonal hematologic disorders characterized by peripheral cytopenia, bone marrow dysplasia, and a risk of leukemic transformation. A hypoplastic variant (MDS-h) shares features with aplastic anemia and responds to immunosuppressive therapy (IST). We report three low-risk MDS-h cases treated with IST and monitored over 9-17 years using serial cytogenetic and molecular analyses. All patients achieved transfusion independence after IST, and two experienced durable, long-term remissions. One patient developed late clonal evolution culminating in secondary acute myeloid leukemia. Molecular follow-up revealed diverse mutational dynamics, including stable and fluctuating clones and delayed mutational emergence, detectable in peripheral blood. These findings suggest that in MDS-h, disease activity is largely driven by immune dysregulation rather than early molecular changes, and that repeated IST can yield sustained remissions. However, accumulating mutations may eventually predict malignant transformation, underscoring the importance of long-term molecular monitoring.
Incidence and Survival of Hemophagocytic Lymphohistiocytosis Over Two Decades: A Population-Based Study.
Lorenzen MOB, Jensen M, Jørgensen RRK … +6 more , Jensen P, Frederiksen H, Hansen DL, El Fassi D, Andersen MN, El-Galaly TC
Eur J Haematol · 2026 Jul · PMID 41910030 · Publisher ↗
Adult hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome triggered by various conditions. A nationwide study of the incidence and outcomes of HLH in Denmark over 23 years (2000-2023) was perfor...
Adult hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome triggered by various conditions. A nationwide study of the incidence and outcomes of HLH in Denmark over 23 years (2000-2023) was performed. Adults (≥ 18 years) with HLH and triggering diseases were identified in the Danish National Patient Registry and/or the Danish Pathology Registry. A total of 325 cases were identified. The incidence increased from 0.82 per 1 million person-years (1 M-PY) (95% CI 0.61-1.04) in 2000-2011 to 4.05 per 1 M-PY (95% CI 3.56-4.53) in 2012-2023. Hematologic malignancies were the triggering diagnosis in 46% of cases, mostly lymphomas (32%). There was no clear improvement in overall survival over time. However, survival differed markedly between subgroups, with the lowest 1-year overall survival of 31% for hematologic malignancy-associated HLH, compared with 75% for idiopathic HLH. In conclusion, HLH remains a rare syndrome with a dismal prognosis, especially when associated with hematologic malignancy.
Treatment-Specific Prediction Models in Multiple Myeloma: A Critical Review of Current Evidence and Future Directions.
Jarrah MM, Al-Shamsi HO, Abuhelwa Z … +6 more , Bustanji Y, Semreen MH, McKinnon RA, Sorich MJ, Hopkins AM, Abuhelwa AY
Eur J Haematol · 2026 Jul · PMID 41909977 · Publisher ↗
BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is characterized by substantial clinical heterogeneity, leading to wide variability in treatment response and toxicity. Although numerous prognostic tools exist, relativel...
BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is characterized by substantial clinical heterogeneity, leading to wide variability in treatment response and toxicity. Although numerous prognostic tools exist, relatively few models estimate outcomes conditional on a specific therapeutic regimen. Treatment-specific prediction models are an important step toward individualized therapy selection. This review synthesizes the current landscape of treatment-specific clinical prediction models in MM. METHODS: A structured search of PubMed and Embase/Scopus identified multivariable clinical prediction models developed within a static treatment framework, evaluating treatment-specific therapeutic or toxicity-related outcomes in MM. Information was extracted on treatment regimens, predictors, modeling methods, validation strategies, and reporting of clinical utility. RESULTS: Thirteen models were identified, evaluating therapeutic (n = 10) or toxicity-related (n = 3) outcomes across regimens including bortezomib-based induction, daratumumab-containing combinations, ixazomib-based triplets, and CAR-T therapy. Predictors were mainly routine clinical and laboratory variables, with limited integration of cytogenetics or patient-reported outcomes. Most models used traditional regression methods; calibration was inconsistently reported, and external validation was performed in seven studies. Decision curve analysis was included in only two models. CONCLUSIONS: Methodological and translational gaps remain, including limited transparency, scarce external validation, and lack of patient-reported or longitudinal predictors. None of the models have been implemented as online calculators or integrated into electronic decision-support systems, limiting real-world uptake. Addressing these gaps is essential for developing clinically meaningful prediction tools to support personalized treatment in MM.
Postoperative Care and Management in Pediatric Hematology-Oncology Patients.
Srivatsa S, Mansfield SA
Eur J Haematol · 2026 Mar · PMID 41881517 · Publisher ↗
Pediatric patients with hematologic and oncologic diseases often undergo surgical procedures as part of diagnosis and therapy. These include central venous catheter placements, tumor resections, lymph node and bone marro...
Pediatric patients with hematologic and oncologic diseases often undergo surgical procedures as part of diagnosis and therapy. These include central venous catheter placements, tumor resections, lymph node and bone marrow biopsies, among others. Optimal postoperative care in this vulnerable population is critical, as children receiving chemotherapy or stem cell transplantation are immunocompromised and at high risk for infections, bleeding, and other complications. This review provides a comprehensive overview of common pediatric hemato-oncologic surgeries and detailed postoperative management strategies. A thorough, multidisciplinary postoperative plan is essential for pediatric hematology-oncology patients to minimize morbidity, avoid delays in adjuvant therapy, and ultimately enhance survival and quality of life.
Venetoclax Combined With Intensive Chemotherapy Regimens for Patients With Relapsed/Refractory Acute Myeloid Leukemia: A Systematic Review and Single-Arm Meta-Analysis.
Goularte MN, Miyamoto MH, de Lacerda MP
Eur J Haematol · 2026 Jul · PMID 41881507 · Publisher ↗
OBJECTIVES: To evaluate the efficacy and safety of venetoclax combined with intensive chemotherapy regimens in patients with relapsed or refractory acute myeloid leukemia (R/R AML) through a systematic review and single-...
OBJECTIVES: To evaluate the efficacy and safety of venetoclax combined with intensive chemotherapy regimens in patients with relapsed or refractory acute myeloid leukemia (R/R AML) through a systematic review and single-arm meta-analysis. METHODS: A systematic search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception to January 2025. Non-randomized studies enrolling R/R AML patients treated with venetoclax plus intensive chemotherapy were included. Pooled rates of complete remission (CR), composite complete remission (CRc), overall response rate (ORR), and adverse events were estimated using random-effects models. Heterogeneity was assessed with I statistics, and sensitivity and subgroup analyses were performed according to chemotherapy regimen. RESULTS: Six retrospective studies comprising 235 patients were included. The pooled CR rate was 27.0% (95% CI, 9.18-57.50; I = 84.6%), CRc rate was 51.45% (95% CI, 36.15-66.76; I = 83.5%), and ORR was 63.79% (95% CI, 49.67-77.92; I = 82.0%). Febrile neutropenia occurred in 71.38% and pneumonia in 23.6% of patients. CONCLUSIONS: Venetoclax combined with intensive chemotherapy demonstrates meaningful antileukemic activity in R/R AML, with an expected toxicity profile. Prospective trials are warranted to define its role relative to standard salvage therapies.
Secondary Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome Following Allo-HCT: Features, Outcomes, and Risk Stratification.
Volkov N, Moiseev I, Krivitskaya M … +11 more , Zhogolev D, Vladovskaya M, Vlasova Y, Bondarenko S, Rudakova T, Ziganshina S, Siniaev A, Beynarovich A, Afanaseva K, Morozova E, Kulagin A
Eur J Haematol · 2026 Jul · PMID 41881489 · Publisher ↗
BACKGROUND: Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a rare but highly fatal complication after allogeneic hematopoietic cell transplantation (allo-HCT), frequently diagno...
BACKGROUND: Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a rare but highly fatal complication after allogeneic hematopoietic cell transplantation (allo-HCT), frequently diagnosed under conditions of clinical uncertainty. We aimed to characterize post-transplant sHLH/MAS and to identify clinically accessible factors associated with early mortality. METHODS: We retrospectively analyzed adult patients who developed sHLH/MAS after allo-HCT between 2018 and 2025. Inclusion required an HScore ≥ 169. Overall survival within 60 days from sHLH/MAS onset was the primary endpoint. Clinical and laboratory variables were evaluated using Cox proportional-hazards models, and patients were stratified according to the number of adverse prognostic factors identified. RESULTS: Seventy-two patients met inclusion criteria. Median time from allo-HCT to sHLH/MAS onset was 22 days. Sixty-day overall survival was poor. In univariable and multivariable analyses, vasopressor-dependent sepsis (HR 7.77, p < 0.001) and ferritin > 15 000 μg/L (HR 3.48, p = 0.002) were independently associated with early mortality. Stratification based on these two factors separated patients into low-, intermediate-, and high-risk groups with 60-day survival of 92%, 52%, and 9%, respectively (p < 0.001). CONCLUSIONS: Post-transplant sHLH/MAS is associated with extremely high early mortality. Vasopressor-dependent sepsis and extreme hyperferritinemia identify patients at particularly high risk. These findings require confirmation in independent cohorts.
Outpatient Delivery of Step-Up Doses to Rapidly Initiate Monthly Doses of Bispecific Antibodies in Multiple Myeloma.
Ramírez-Alvarado AG, Varela-Constantino A, Gómez-Almaguer D … +10 more , Ovilla-Martínez R, Alvarado-Ibarra M, Pérez-Zincer F, Ramos-Peñafiel C, Cruz D, Solano-Genesta M, Del Carmen López-Sánchez M, Barranco-Lampon GI, García-Castillo C, Vela-Ojeda J
Eur J Haematol · 2026 Jul · PMID 41881461 · Publisher ↗
AIMS: New therapies are improving outcomes even in advanced stages of multiple myeloma. OBJECTIVES: To describe the experience of bispecific antibodies (BsAbs) in Mexico. RESULTS: The study included 41 patients with trip...
AIMS: New therapies are improving outcomes even in advanced stages of multiple myeloma. OBJECTIVES: To describe the experience of bispecific antibodies (BsAbs) in Mexico. RESULTS: The study included 41 patients with triple-class refractory (88%) and penta-drug refractory (61%) myeloma. The median number of prior treatment lines was 3, and the median time to response was 2 months. Step-up dosages were administered on an outpatient basis in 34 patients (83%). BsAbs were administered every 2 weeks to 19 patients (46%) and monthly to 17 patients (41.5%). Thirteen of these (31.5%) switched to monthly doses early in treatment and maintained their response. Twenty-five of 38 evaluated patients (66%) achieved a complete response or better, and 84% were negative for minimal residual disease. The median response duration was 10 months, while median progression-free survival and overall survival were 12 and 13 months, respectively. Extramedullary disease, no complete response, positivity for minimal residual disease, and penta-refractoriness were associated with poor outcomes. The adverse events were lower than those reported in clinical trials. CONCLUSIONS: In conclusion, using outpatient step-up dosing followed by planned de-escalation to monthly doses of BsAbs in responding patients with MM is feasible, safe, and effective, and may improve access to this novel therapy.
Intravascular Large B-Cell Lymphoma: Clinicopathological Characteristics and Outcomes.
García CR, Campuzano DM, Ruiz ABG … +5 more , Moreno ES, González SM, Pia JMC, Lapiedra RA, Fontestad NR
Eur J Haematol · 2026 Jul · PMID 41872720 · Publisher ↗
Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma with a poor prognosis. This retrospective study reports the clinicopathological characteristics and outcomes of six cases of IVLBCL diagnosed in a period of...
Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma with a poor prognosis. This retrospective study reports the clinicopathological characteristics and outcomes of six cases of IVLBCL diagnosed in a period of 8 years in a tertiary hospital. The mean age was 66 years, with no sex predilection. Dizziness, gait instability, and hepatosplenomegaly were the most common presentations. Laboratory and brain imaging findings were inconclusive for lymphoma in all cases. Brain biopsies were diagnostic in two cases, while skin biopsies led to diagnosis in three patients. Only one patient with hemophagocytic variant was diagnosed at autopsy. Histologically, atypical lymphocytes infiltrated deep small- and medium-sized vessels, showing positive staining for B-cell markers. All patients who received combined chemotherapy achieved a complete response. After a median follow-up of 4 years, four of six patients remain alive. This lymphoma represents a diagnostic challenge, requiring a high index of suspicion and a multidisciplinary approach.
Real-World Safety and Efficacy of Avatrombopag in Adults with Immune Thrombocytopenia: A Systematic Review and Meta-Analysis.
Lozano ML, Valcarcel D
Eur J Haematol · 2026 Jul · PMID 41863412 · Publisher ↗
OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the risk of thromboembolic events and assess the overall safety and effectiveness of avatrombopag in adult patients with immune thrombocytopenia using...
OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the risk of thromboembolic events and assess the overall safety and effectiveness of avatrombopag in adult patients with immune thrombocytopenia using real-world evidence. METHODS: A systematic search was conducted following the PRISMA 2020 guidelines. Observational studies (2020-2024) on adults with primary immune thrombocytopenia treated with avatrombopag were included. Primary outcomes were thromboembolic complications and treatment response; secondary outcomes included time to response, treatment discontinuation, and adverse events. Random-effects meta-analyses were performed to synthesise pooled proportions and rates. Risk of bias was assessed using the ROBINS-Version 2 tool. RESULTS: Fifteen studies were included. The pooled proportion of patients with thromboembolic events was 2.82% (95% confidence interval: 1.61%-4.27%), with an incidence rate of 3.29 per 100 patient-years (95% CI: 1.81-5.08). Response and complete response were achieved by 80.0% and 92.0% of patients, respectively. The median time to response was 11 days, and the discontinuation rate was 18.9%. Adverse events occurred in 4.1% of patients. CONCLUSION: In real-world practice, avatrombopag demonstrated high platelet response rates and a low pooled incidence of thrombotic events. These findings add real-world evidence on avatrombopag outcomes in adult immune thrombocytopenia.
Prevention and Management of Acute Chest Syndrome Without Automated Red Cell Exchange Among Patients With Sickle Cell Disease Not Requiring ICU Care: A Systematic Review and Network Meta-Analysis.
Alsabri M, Al-Tawil M, Abdelgalil MS … +9 more , Elsnhory AB, Fayoud AM, Ramadan S, Elshanbary AA, Mohamed NS, AlAttar O, Pyala R, Aboali AA, Abdelwahab OA
Eur J Haematol · 2026 Jul · PMID 41857793 · Publisher ↗
Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) associated with significant morbidity and mortality, necessitating optimized prevention and management strategies for improved patient outc...
Acute chest syndrome (ACS) is a severe complication of sickle cell disease (SCD) associated with significant morbidity and mortality, necessitating optimized prevention and management strategies for improved patient outcomes. This review does not evaluate red blood cell exchange, as no randomized controlled trials meeting our inclusion criteria reported outcomes for this intervention. A thorough literature review identified interventions for ACS in SCD patients. Seventeen randomized controlled trials (RCTs) underwent assessment using the Cochrane Risk of Bias 2 tool, and a frequentist network meta-analysis was conducted to compare interventions. The use of hydroxyurea and simple transfusion was associated with a lower proportion of patients who developed ACS during the study period compared with standard care (RR: 0.42, 95% CI [0.20-0.86]; RR: 0.31, 95% CI [0.12-0.75], respectively). Intravenous dexamethasone was associated with a lower risk of persistent fever, reduced need for blood transfusion, and shorter durations of both opioid and oxygen therapy, as well as a shorter in-hospital stay (p < 0.01 for all comparisons). When compared with standard care, hydroxyurea was associated with reduced requirement for blood transfusion (RR: 0.17, 95% CI [0.04, 0.73]), with a similar association observed for intravenous dexamethasone (RR: 0.19, 95% CI [0.05, 0.77]). No significant associations were identified between any treatment and rates of hospitalization or readmission. This study offers insights into ACS treatment efficacy and safety in SCD patients. Hydroxyurea and transfusion strategies demonstrated the strongest evidence for reducing acute chest syndrome risk. Corticosteroids were associated with improved inpatient outcomes in predominantly pediatric populations, but concerns regarding potential rebound pain and rehospitalization warrant cautious interpretation. Larger trials are required before routine steroid use can be broadly recommended.
Patient-Reported Outcomes With Luspatercept Through 5 Years of Treatment in Patients With Non-Transfusion-Dependent β-Thalassemia Treated in the BEYOND Trial.
Musallam KM, Cappellini MD, Kattamis A … +10 more , Dyer M, Hnoosh A, Eliason L, Pelligra CG, Guo S, Mu Y, Medlin LF, Reverte M, Kuo KHM, Taher AT
Eur J Haematol · 2026 Jul · PMID 41857682 · Publisher ↗
In the phase 2, double-blind, randomized controlled BEYOND trial (NCT03342404), luspatercept increased hemoglobin levels in patients with non-transfusion-dependent β-thalassemia (NTDT). This study assessed long-term effe...
In the phase 2, double-blind, randomized controlled BEYOND trial (NCT03342404), luspatercept increased hemoglobin levels in patients with non-transfusion-dependent β-thalassemia (NTDT). This study assessed long-term effects of luspatercept on patient-reported outcomes (PROs), using data from BEYOND and patients who continued luspatercept treatment in the phase 3b long-term follow-up (LTFU) study (NCT04064060). In BEYOND, patients received luspatercept or placebo Q3W for ≥ 48 weeks. PRO instruments included NTDT-PRO (BEYOND only), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and 36-Item Short Form Survey (SF-36). Mixed-effects models with repeated measures estimated least squares mean changes from baseline in PROs. PROs were evaluable in 144 patients (luspatercept 95, placebo 49) from BEYOND and 58 (luspatercept) from LTFU. Luspatercept improved NTDT-PRO tiredness/weakness and shortness of breath domain, FACIT-F fatigue subscale, and SF-36 vitality scores versus placebo through double-blind treatment (generally maintained through week 96). In LTFU patients, significant, meaningful improvements from baseline in FACIT-F fatigue subscale and SF-36 vitality scores were observed within 12 weeks of treatment initiation and maintained for up to 5 years. Other FACIT-F and SF-36 domains improved or were maintained throughout LTFU. Luspatercept offers rapid and durable benefits by improving anemia-related symptoms and quality of life in patients with NTDT. Trial Registration: ClinicalTrials.gov Identifier: NCT03342404; NCT04064060.
The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma.
Barachini S, Cassano Cassano R, Ronca F … +3 more , Petrini I, Galimberti S, Buda G
Eur J Haematol · 2026 Jul · PMID 41856486 · Publisher ↗
Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells h...
Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells have recently emerged as highly effective therapies in relapsed/refractory MM, inducing deep responses even in heavily pretreated patients. However, disease relapse, limited durability of response, and treatment-related toxicities remain frequent, underscoring the need to better understand mechanisms of resistance. Accumulating evidence indicates that the tumor microenvironment (TME) plays a central role in shaping BsAb efficacy in MM. Immunosuppressive cellular components, including regulatory T-cells, myeloid-derived suppressor cells, and dysfunctional antigen-presenting cells, as well as inhibitory cytokines, hypoxia, and metabolic constraints within the TME, profoundly impair T-cell activation, expansion, and persistence following BsAb engagement. In addition, chronic CD3 stimulation within the TME may promote T-cell exhaustion, contributing to suboptimal responses and disease progression. This review focuses on the dynamic interplay between BsAbs and the MM TME, highlighting how microenvironment-driven immune suppression, antigen escape, and impaired T-cell fitness influence clinical outcomes. We further discuss emerging strategies designed to overcome these barriers, including rational combination approaches, immunomodulatory agents, and next-generation trispecific antibodies that enhance co-stimulation or dual-antigen targeting. Understanding and therapeutically modulating the TME represents a critical step toward improving the depth, durability, and safety of BsAb-based therapies in MM.
Digital Surveillance After Allogeneic Hematopoietic Stem Cell Transplantation Guides Therapeutic Interventions to Reduce Non-Relapse Mortality.
Bischof L, Egger-Heidrich K, Schneider M … +15 more , Friedrich G, Massow A, Vogelsang J, Schmidt F, Hänel M, Illmer T, Leppla L, Teynor A, de Geest S, Muelller G, Metzeler KH, Bornhäuser M, Platzbecker U, Middeke JM, Vučinić V
Eur J Haematol · 2026 Jun · PMID 41847738 · Full text
INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) offers curative potential for many hematological malignancies; however, outcomes may be adversely affected by infections and transplant-associated c...
INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) offers curative potential for many hematological malignancies; however, outcomes may be adversely affected by infections and transplant-associated complications, contributing to non-relapse mortality (NRM). Innovative digital approaches for outpatient surveillance may support earlier detection of complications and thereby help reduce NRM. CASE PRESENTATION: We report on a 73 year-old Caucasian patient who underwent allogeneic HSCT for acute myeloid leukemia in complete remission following non-myeloablative conditioning. The patient participated in the interventional study "Cross-sectoral care for patients with hematological diseases following innovative cell therapy" (SPIZ), which evaluates digital surveillance after cellular therapies. SPIZ comprises daily remote monitoring of vital signs, medication adherence, and symptoms using a multimodal approach integrating an eHealth system (patient smartphone app and caregiver monitoring dashboard), home visits, video consultations, and regular case conferences with referring physicians during follow-up. Eight months post-HSCT, during an inpatient stay at an orthopedic rehabilitation center, the patient reported increasing dyspnea and cough via the app. In response, the SPIZ team initiated immediate transfer to the transplant center. Diagnostic work-up revealed pneumonia caused by aspergillus fumigatus and coronavirus, and progression of pre-existing pulmonary graft-versus-host disease (GvHD), confirmed by computed tomography and spiroergometry. Early detection and prompt transfer enabled rapid initiation of antifungal therapy and intensified GvHD management. The patient was discharged with improved general condition and respiratory function, without further septic complications. CONCLUSION: Innovative digital surveillance is an effective tool for outpatient monitoring after cellular therapies, facilitating early detection and intervention and potentially reducing NRM, particularly in high-risk patients.
Advances and Challenges in the Multidisciplinary Treatment of Retroperitoneal Infantile Fibrosarcoma in Early Life.
Brunetti G, Zarfati A, Persano G … +6 more , Milano GM, Russo I, Natali GL, Alaggio R, Crocoli A, Grimaldi C
Eur J Haematol · 2026 Mar · PMID 41846581 · Publisher ↗
BACKGROUND AND AIMS: Retroperitoneal Infantile Fibrosarcoma (RIFS) is a rare, locally aggressive pediatric soft tissue tumor. Its retroperitoneal location poses challenges due to proximity and potential invasion of criti...
BACKGROUND AND AIMS: Retroperitoneal Infantile Fibrosarcoma (RIFS) is a rare, locally aggressive pediatric soft tissue tumor. Its retroperitoneal location poses challenges due to proximity and potential invasion of critical structures such as the inferior vena cava (IVC). This study aims to illustrate the range of multidisciplinary management strategies and evolving therapeutic approaches. METHODS: We conducted a retrospective case series of infants diagnosed with RIFS and treated at our tertiary center. Clinical presentation, imaging findings, histopathology, treatment modalities (including chemotherapy, surgery, interventional radiology, targeted therapies), and follow-up data were analyzed. RESULTS: Three infants with histologically confirmed RIFS were identified, with a median age at diagnosis of 2 months (range: 0-8 months). Diagnosis was established through open surgical biopsy. Management was individualized and multimodal, including neoadjuvant chemotherapy, surgical resection, interventional radiology procedures for symptom control, and, in the most recent case, targeted molecular therapy guided by genetic profiling. CONCLUSIONS: Management of RIFS has significantly evolved over the last decade. Advances in surgical techniques combined with the integration of interventional radiology and novel targeted therapies allow a nuanced balance between maximizing oncological control and minimizing surgical morbidity. Multidisciplinary individualized treatment is essential to optimize outcomes in this rare and challenging pediatric tumor.
Surgical Aspects of Patients With Leukemic Testicular Infiltration.
Albuquerque TM, Sousa AVL, Rollo G … +6 more , Adriano FKMS, Zarfati A, Persano G, Lederman HM, Crocoli A, Abib SCV
Eur J Haematol · 2026 Mar · PMID 41846574 · Publisher ↗
Leukemia is the most common childhood cancer, accounting for one-third of malignancies in this age group. Testicular infiltration in pediatric leukemia patients represents a manifestation of leukemic dissemination beyond...
Leukemia is the most common childhood cancer, accounting for one-third of malignancies in this age group. Testicular infiltration in pediatric leukemia patients represents a manifestation of leukemic dissemination beyond the bone marrow and can occur at diagnosis or be a sign of relapse. Testicular infiltration may occur particularly in specific leukemia subtypes, such as acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) and is an important prognostic factor, as it may indicate an increased risk of leukemia relapse. Therefore, rigorous follow-up is essential to detect testicular infiltration early and initiate appropriate treatment. This study aims to evaluate cases of leukemia with testicular infiltration in two pediatric oncology referral centers in two different countries. We conducted a retrospective study of patients presenting with secondary testicular infiltration due to leukemia over a 14-year period (January 2010 to December 2023). During the study period, we identified 24 patients who developed testicular infiltration secondary to leukemia. All cases of testicular infiltration were diagnosed at the time of disease relapse. Fourteen patients presented with isolated testicular relapse, while the remaining patients had additional relapse sites in combination with testicular recurrence: bone marrow (10 cases) and central nervous system (2 cases). The mean age at diagnosis was 7.91 years. The average leukocyte count at diagnosis was 56 211/mm, with only five patients presenting with leukocyte counts above 100 000/mm. Four children (16.6%) were diagnosed with T-cell ALL, 20 (83.4%) with B-cell ALL. Fifteen patients (62.5%) underwent hematopoietic stem cell transplantation, including two haploidentical transplants. Twelve patients (50%) died-three due to disease progression and one from disseminated fusariosis. Data regarding the cause of death were unavailable for the remaining patients. The average follow-up duration was 5.87 years, with an event-free survival of 2.085 years. Although rare, testicular infiltration in leukemia patients is a clinically significant phenomenon that may affect both prognosis and quality of life. Early diagnosis and appropriate treatment of the underlying leukemia are crucial to improve outcomes. Monitoring of testicular function and fertility-related concerns must also be addressed comprehensively in patient management. Future studies with larger cohorts and standardized management protocols are essential to establish clear guidelines for the diagnosis, treatment, and follow-up of patients with testicular relapse secondary to ALL. Given the low number of cases and the diversity of local resources worldwide (especially regarding radiotherapy and endocrine follow up), the best approach for each patient should be determined in multidisciplinary team discussions.
Elranatamab in Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Emerging Perspectives.
Alvaro ME, Martino EA, Caserta S … +10 more , Skafi M, Bruzzese A, Amodio N, Lucia E, Olivito V, Labanca C, Mendicino F, Vigna E, Morabito F, Gentile M
Eur J Haematol · 2026 Jul · PMID 41846541 · Publisher ↗
Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies...
Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. Targeting B-cell maturation antigen (BCMA) has emerged as an effective therapeutic strategy, prompting the development of bispecific antibodies that redirect T-cell cytotoxicity toward malignant plasma cells. Elranatamab is a humanized BCMA × CD3 bispecific antibody that has demonstrated clinically meaningful activity in heavily pretreated RRMM. This review summarizes and critically appraises available evidence on elranatamab, focusing on its mechanism of action, clinical efficacy, safety profile, patient-reported outcomes, and comparative positioning within the evolving BCMA-directed treatment landscape. Across studies, elranatamab has shown high response rates, durable disease control, and manageable toxicity, with predominantly low-grade cytokine release syndrome and limited neurotoxicity when administered with step-up dosing. Emerging data indicate preserved efficacy in patients previously exposed to BCMA-targeted therapies and feasibility in selected high-risk populations, including those with severe renal impairment. Nevertheless, uncertainties remain regarding optimal sequencing, long-term survival benefit, infection risk management, and mechanisms of resistance. Overall, elranatamab represents a valuable addition to the therapeutic armamentarium for RRMM. Ongoing studies and real-world experience will be critical to refine its positioning, identify patients most likely to benefit, and define its role in combination strategies.
Ph-Negative Acute Lymphoblastic Leukemia in the Older Adults: Biology, Therapeutic Strategies and Unmet Needs.
Bruzzese A, Vigna E, Martino EA … +10 more , Caserta S, Mendicino F, Alvaro ME, Labanca C, Lucia E, Olivito V, Fiorillo M, Amodio N, Morabito F, Gentile M
Eur J Haematol · 2026 Jul · PMID 41833299 · Publisher ↗
Acute lymphoblastic leukaemia (ALL) in older adults represents a growing clinical challenge, driven by an ageing population, adverse disease biology, and reduced tolerance to intensive chemotherapy. Although pediatric-in...
Acute lymphoblastic leukaemia (ALL) in older adults represents a growing clinical challenge, driven by an ageing population, adverse disease biology, and reduced tolerance to intensive chemotherapy. Although pediatric-inspired regimens have improved outcomes in younger adults with Philadelphia chromosome (Ph)-negative ALL, survival in older patients remains poor, with high rates of treatment-related toxicity, early death, and relapse. Age-related comorbidities, impaired organ function, and unfavorable cytogenetic and molecular features, including low hypodiploidy and TP53 mutations, further compromise prognosis. In this context, monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin (InO), used alone or in combination with reduced-intensity chemotherapy, have emerged as promising frontline approaches capable of deep remissions with improved tolerability. Moreover, CAR T-cell therapy is increasingly recognized as a potentially effective strategy for relapsed/refractory disease in selected older adults, particularly in the setting of low disease burden, with acceptable safety in carefully monitored cohorts. However, issues such as antigen loss, lineage switch, the management of T-cell ALL, and the optimal sequencing of immunotherapies remain unresolved. Across all treatment strategies, comprehensive geriatric assessment appears more informative than performance status alone in predicting tolerability and outcome, supporting its integration into trial design and routine decision-making. Overall, the refinement of immunotherapeutic approaches, coupled with biologically and geriatrically tailored treatment algorithms, offers the most promising avenue to improve long-term outcomes for older patients with ALL.
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