Peri AM, Henden AS, Nelles R
… +4 more, Chatfield MD, Harris PNA, Kennedy G, Paterson DL
Eur J Haematol
· 2026 May · PMID 41577624
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BACKGROUND: Managing febrile neutropenia is challenging due to the limited sensitivity of blood culture (BC) and the lack of tools differentiating infectious from non-infectious fever. T2 magnetic resonance (T2MR) is a c...BACKGROUND: Managing febrile neutropenia is challenging due to the limited sensitivity of blood culture (BC) and the lack of tools differentiating infectious from non-infectious fever. T2 magnetic resonance (T2MR) is a culture-independent system detecting bacteria (T2Bacteria) and yeasts (T2Candida); SeptiCyte RAPID is a host response assay providing a likelihood of sepsis (SeptiScore). METHODS: We conducted an observational study including bone marrow transplant patients with febrile neutropenia to assess (1) the performance of T2MR versus BC (2) the performance of SeptiScore in providing valid results and diagnosing infection compared to a retrospective clinician diagnosis. RESULTS: We included 90 febrile episodes. Eleven episodes had BC growing bacteria, of which 3/11 were T2Bacteria on-panel pathogens. T2Candida identified four Candida with a turnaround time of 3.0 h (IQR 3.0-3.0), significantly shorter than BC (42.4 h, IQR 39.8-50.9, p = 0.014). A SeptiScore was obtained in 86/90 cases. Febrile episodes were classified as: infectious (21/86, 24%), probably infectious (13/86, 15%), indeterminate (excluded from analysis; 40/86, 46%), non-infectious (12/86, 14%). The AUC of SeptiScore for infectious fever was 0.84 (95% CI 0.71-0.97). CONCLUSION: Despite the short turnaround time, T2MR showed limited coverage of bloodstream pathogens. SeptiScore may help in diagnosing infectious neutropenic fever, but larger studies should clarify its clinical utility.
OBJECTIVES: Adult T-cell leukemia (ATL), caused by human T-cell leukemia virus type 1 (HTLV-1), has a poorer prognosis than other peripheral T-cell lymphomas. Phosphorylation of highly expressed in cancer 1 (Hec1) by NIM...OBJECTIVES: Adult T-cell leukemia (ATL), caused by human T-cell leukemia virus type 1 (HTLV-1), has a poorer prognosis than other peripheral T-cell lymphomas. Phosphorylation of highly expressed in cancer 1 (Hec1) by NIMA-related kinase 2 (Nek2) is essential for mitosis. This study evaluated the therapeutic potential of Nek2 and Hec1 inhibitors in ATL. METHODS: Cell proliferation, survival, cell cycle progression, apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) were assessed. Expression of Nek2, Hec1, and related signaling proteins was also analyzed. RESULTS: Nek2 and Hec1 were upregulated in HTLV-1-infected T-cell lines and in normal peripheral blood mononuclear cells after infection. Knockdown of Nek2 or treatment with Nek2/Hec1 inhibitors (INH154, T-1101 tosylate) or the Nek2 inhibitor MBM-55S reduced proliferation and survival. INH154 induced Nek2 degradation and G1-phase arrest, accompanied by downregulation of CDK2/4, cyclin D2/E, c-Myc, and phospho-pRb, and upregulation of p53. It also triggered apoptosis via caspase activation, downregulation of Mcl-1, survivin, and c-IAP2, and upregulation of Bax and Bak. Additionally, INH154 induced necroptosis, ROS accumulation, DNA damage, mitochondrial dysfunction, and suppression of β-catenin and NF-κB/AP-1 signaling. CONCLUSION: Aberrant expression of Nek2 and Hec1 may contribute to ATL pathogenesis.
The field of acute myeloid leukemia (AML) therapeutics has seen significant progress with respect to the development of targeted agents for specific mutational subsets. However, outcomes for patients with high-risk AML r...The field of acute myeloid leukemia (AML) therapeutics has seen significant progress with respect to the development of targeted agents for specific mutational subsets. However, outcomes for patients with high-risk AML remain dismal, and curative intent therapy is often challenging to administer in this population. AML is a highly plastic entity that employs a variety of mechanisms to circumvent immunosurveillance. In the recent decade, preclinical evidence for chimeric antigen receptor-T (CAR-T) and chimeric antigen receptor-natural killer (CAR-NK) therapies has gained traction in a variety of other hematologic malignancies, but the translation of these therapies to patients with AML has been limited. In this review, we discuss contemporary challenges to the clinical translation of cell-based therapeutics in AML. We underscore practical solutions to facilitating the clinical availability of novel cell-based therapies in AML. These solutions include widening the narrow therapeutic window through better myeloid-specific CAR target validation, developing multi-antigen or tandem CAR products, optimizing the immune repertoire and bone marrow niche in AML, and enhancing scalability of cell-based therapeutics such that patients in local communities can benefit from ongoing efforts. These strategies may help improve the translational success of CAR-T and CAR-NK therapies in AML in the coming years.
OBJECTIVES: Comparisons of safety and efficacy of Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following complete remission (CR) achieved by Chimeric antigen receptor T (CAR-T) cell therapy versus chemo...OBJECTIVES: Comparisons of safety and efficacy of Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following complete remission (CR) achieved by Chimeric antigen receptor T (CAR-T) cell therapy versus chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) have not been fully discussed. METHODS: We performed a comparison of transplant outcomes in 443 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n = 50) or with chemotherapy (n = 393). The median follow-up time was 30 months (range: 1-62 months). RESULTS: The CAR-T group had a lower incidence of chronic graft-versus-host disease (30.9% vs. 44.0%, p = 0.020). We also found that the incidence of veno-occlusive disease was higher in the CAR-T group compared to the chemotherapy group (4% vs. 0.5%; p = 0.003). The study revealed that both the CAR-T and chemotherapy groups exhibited comparable overall survival (90.9% vs. 94.6%, p = 0.158) and relapse incidences (9.1% vs. 8.4%, p = 0.513). However, incidences of non-relapse mortality after transplantation were higher in the CAR-T group (10.9% vs. 4.3%, p = 0.016), and leukemia-free survival was lower in the CAR-T group compared to the chemotherapy group (80.0% vs. 86.8%, p = 0.040). CONCLUSIONS: Our data indicate that, in B-ALL patients, most treatment-related complications and survival were comparable between CAR T-cell therapy and chemotherapy followed by allo-HSCT.
Blüm P, Glas C, Bieback K
… +3 more, Kayser S, Klüter H, Wuchter P
Eur J Haematol
· 2026 May · PMID 41553051
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INTRODUCTION: Cryopreservation of peripheral-blood-derived hematopoietic stem and progenitor cells (PBSCs) has been used for decades, primarily for autologous transplantation. Now, in the era of new cellular therapies, t...INTRODUCTION: Cryopreservation of peripheral-blood-derived hematopoietic stem and progenitor cells (PBSCs) has been used for decades, primarily for autologous transplantation. Now, in the era of new cellular therapies, the cryopreservation of allogeneic PBSCs may also become relevant. While the defining quality-control parameters are assessed before cryopreservation, in thawed cryopreserved samples the viability of total nucleated cells is often the only parameter analyzed. We therefore evaluated the recovery rates of total and viable CD45 and CD34 cells after cryopreservation. METHODS: Thirty-nine samples of allogeneic PBSC products were analyzed before and after cryopreservation. Post-thaw viability was assessed using trypan blue exclusion. To investigate the influence of different preanalytical preparation methods, PBSCs were resuspended in phosphate-buffered saline (PBS) or human serum albumin (HSA), and the cells suspended in HSA were tested without incubation or following incubation at 37°C for 1 h or 2 h. The number and viability of CD45 and CD34 cells were evaluated by flow cytometry and compared with pre-thaw values. RESULTS: After cryopreservation, we observed significant decreases in both total and viable CD45 cell numbers. In contrast, the difference in total CD34 cell numbers was rather small, whereas the median recovery rate of viable CD34 cells after resuspension in PBS was 70.1%. Relevant differences between the preanalytical treatment groups could not be observed. The viability values as determined by trypan blue viability staining and flow cytometry were not correlated. CONCLUSION: Determination of the CD34 cell recovery rate after thawing is feasible and may be used as an additional parameter for quality control for cryopreserved allogeneic PBSCs. However, the results of currently used viability assays vary considerably, making comparisons between different cell processing units and cryopreservation protocols difficult. Therefore, available protocols should be carefully evaluated based on "good-manufacturing-practice" (GMP) regulations before implementation.
Chimeric antigen receptor T cells (CAR-T) have been associated with prolonged hematotoxicity known as late immune effector cell-associated hematologic toxicity (ICAHT), but there is limited literature on its duration and...Chimeric antigen receptor T cells (CAR-T) have been associated with prolonged hematotoxicity known as late immune effector cell-associated hematologic toxicity (ICAHT), but there is limited literature on its duration and clinical implications. We conducted a retrospective review of 156 adults who received CD19-directed CAR-T therapy at The Ottawa Hospital between 2019 and 2024. Late ICAHT occurred in 39% (95% CI 31%-47%) of recipients, with a duration ranging from 6 to 1473 days. Cumulative incidence analysis, censoring for disease progression and death, yielded a median duration of 183 days, with 20% (95% CI 11%-38%) experiencing ICAHT lasting over 1 year. Overall survival was comparable between patients with and without late ICAHT. In univariate analysis, HEMATOTOX score was significantly associated with the development of late ICAHT. Among a subset of 13 patients assessed for resource utilization, growth factors were the primary cost driver. Patients required frequent follow-up, with a median of 1 in every 7 days involving an in-person healthcare encounter. Late ICAHT was a common but usually self-limited toxicity. The 30-day cutoff currently used to define late ICAHT should be compared to later cutoffs to evaluate whether it improves the characterization of ICAHT's clinical impact on outcomes and healthcare utilization.
Mansour R, Green KM, Graf C
… +12 more, Chang M, Magee G, Davis JA, Zayad A, Ahmed N, Mushtaq MU, Ouchveridze E, Mahmoudjafari Z, Paul B, Twardowski N, Atrash S, Abdallah AO
BACKGROUND: Patients aged ≥ 70 years with relapsed/refractory multiple myeloma (RRMM) face unique challenges due to physiological changes and increased toxicity from treatments. Daratumumab-based regimens have shown effi...BACKGROUND: Patients aged ≥ 70 years with relapsed/refractory multiple myeloma (RRMM) face unique challenges due to physiological changes and increased toxicity from treatments. Daratumumab-based regimens have shown efficacy, but direct comparisons in elderly populations are lacking. METHODS: A multicenter retrospective study compared daratumumab, pomalidomide, and dexamethasone (DPd) to daratumumab, carfilzomib, and dexamethasone (DKd) in patients with RRMM aged ≥ 70 years. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and response rates. RESULTS: The study included 150 patients (119 DPd, 31 DKd). Baseline characteristics were similar, but DPd had more lenalidomide-refractory patients (90% vs. 74%, p = 0.035). Overall response rates were comparable (DPd 77%, DKd 74.5%, p = 0.8), but DKd had a significantly higher rate of deep responses (64.5% vs. 36%, p < 0.01). Median PFS was 12 months for DPd and 13 months for DKd (p = 0.6); median OS was 50 months for DPd and 28 months for DKd (p = 0.2). Multivariate analysis identified poor performance status and high-risk cytogenetics as adverse prognostic factors. CONCLUSION: DPd and DKd showed similar efficacy for elderly RRMM patients, with DKd achieving deeper responses. Treatment decisions should consider individual patient factors rather than focusing solely on efficacy differences.
Corso A, Marchetti M, Galli M
… +35 more, Barilà G, Conticello C, Belotti A, Antonioli E, Botta C, Bringhen S, Cafro AM, Cea M, Derudas D, Furlan A, Gentile M, Giuliani N, Crimi F, Esposito A, Mancini P, Zacchino M, Frittoli B, Gozzetti A, Liberatore C, Mangiacavalli S, Mannina D, Rago A, Mele G, Montefusco V, Offidani M, Patriarca F, Pescosta N, Petrucci MT, Ria R, Tosi P, Vincelli D, Buda G, Zamagni E, di Toritto TC, Zambello R
OBJECTIVES: Using suboptimal imaging modalities on the detection of bone and extra-bone myeloma lesions affects disease status recognition and early treatment decisions. Moreover, a systematic search of the evidence was...OBJECTIVES: Using suboptimal imaging modalities on the detection of bone and extra-bone myeloma lesions affects disease status recognition and early treatment decisions. Moreover, a systematic search of the evidence was not provided alongside the recommendations. The objective of this study was to assess the current real world imaging practices in Italy, influencing factors, and barriers to adopting international imaging guidelines for MGUS and MM (reported as plasma cell disorders, PCD) and to develop evidence-based, country-specific recommendations for imaging assessment of PCD patients. METHODS: A national project was launched in 2024, involving experts from 32 hematology centers and 5 radiology services. A survey was conducted and a Delphi panel comprising 23 experts was used to reach a consensus on the developed recommendations. A total of 25 recommendations were finally formulated. RESULTS: The survey revealed that suboptimal imaging modalities were significantly contributing to the under-recognition of bone and extra-bone lesions in myeloma, leading to suboptimal disease status assessment and treatment decisions. CONCLUSIONS: The study emphasizes the importance of adopting effective imaging modalities to improve disease detection and guide treatment decisions in PCD patients. A country-specific, evidence-based set of imaging recommendations has been developed to address existing challenges in the adoption of international imaging guidelines.
BACKGROUND: Vulvovaginal chronic graft-versus-host disease (vv-cGvHD) is an underrecognised complication after allogeneic haematopoietic stem cell transplantation (HSCT), with potential impact on sexual function, quality...BACKGROUND: Vulvovaginal chronic graft-versus-host disease (vv-cGvHD) is an underrecognised complication after allogeneic haematopoietic stem cell transplantation (HSCT), with potential impact on sexual function, quality of life, and long-term morbidity. Few prospective data are available in the literature based on systematic gynaecological assessment. MATERIAL AND METHODS: A prospective, observational, single-centre study was carried out to evaluate 1-year incidence and clinical features of vv-cGvHD in female patients undergoing HSCT among patients alive and relapse-free at day + 100. Standardised gynaecological examinations were performed at baseline, day + 100, 6, and 12 months. Data collection included patient-reported outcomes by use of a symptom-focused questionnaire to assess the presence and impact of vv-cGvHD. RESULTS: Forty-one evaluable patients were included in the analysis and followed with scheduled gynaecological evaluations at defined intervals post-transplant. Vv-cGvHD was diagnosed in 12 out of 41 patients (29.3%), with six cases classified as grade 1 and six as grade 2 according to NIH criteria. The conditional cumulative incidence at 1 year was 30%. Half of the affected patients presented isolated genital involvement, without other cGvHD manifestations. Median onset was 6 months post-transplant. Chronic GvHD in other organs was the only factor associated with vv-cGvHD in univariate analysis (p = 0.02). Topical treatment with corticosteroids and hyaluronic acid was administered to 75% (n = 9) of affected patients, with no cases progressing to severe disease requiring surgical intervention. CONCLUSION: This study highlights a considerable incidence of vv-cGvHD among HSCT recipients, underlining the need for systematic screening and management protocols.
Sharma R, Atenafu EG, Masih-Khan E
… +11 more, Vohra H, Bhella S, Chen C, Kukreti V, Lancman G, Prica A, Stewart AK, Tiedemann R, Trudel S, Yang C, Reece D
Eur J Haematol
· 2026 May · PMID 41536023
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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...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.
This is a plain language summary describing results from the Alfa-PROTECT study on safety and efficacy of damoctocog alfa pegol in previously treated children aged between 7 and 12 years with severe haemophilia A. Trial...This is a plain language summary describing results from the Alfa-PROTECT study on safety and efficacy of damoctocog alfa pegol in previously treated children aged between 7 and 12 years with severe haemophilia A. Trial Registration: The Alfa-PROTECT trial is registered at ClinicalTrials.gov: NCT05147662.
Larsson AE, Renlund H, Andréasson B
… +3 more, Holmberg H, Liljeholm M, Själander A
Eur J Haematol
· 2026 May · PMID 41531010
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BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with a well-recognized increased risk of thrombotic events, bleeding, and all-cause mortality, but the frequency of these outcomes duri...BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with a well-recognized increased risk of thrombotic events, bleeding, and all-cause mortality, but the frequency of these outcomes during treatment has rarely been assessed in large cohorts. METHODS: In this nationwide, population-based study, we analyzed 2604 PV and 3141 ET patients using multiple Swedish health care registers, covering 43 612 patient-years. Rates of arterial and venous events, major bleeding, and all-cause mortality (ACM) were evaluated across therapies. RESULTS: Unexpectedly, 42.3% of low-risk PV patients and 29.7% of very low/low-risk ET patients received hydroxyurea (HU) during follow-up. High-risk PV patients treated with interferon (IFN) exhibited the lowest arterial event rate (2.21 per 100 patient-years). In high-risk ET, patients with IFN therapy experienced the lowest arterial and venous event rates (1.55 and 0.44 per 100 patient-years). Advanced age and leukocytosis at diagnosis independently predicted thrombosis, bleeding, and ACM in both PV and ET. Multivariable analysis showed that HU and IFN were associated with reduced ACM risk; HU also conferred protection against thromboembolism and major bleeding. CONCLUSION: This study highlights risk factors associated with complications during treatment in a real-world context and reinforces the role of HU and IFN as first-line therapies in PV and ET.
Puig N, Leleu X, Lee HC
… +16 more, Davies FE, Hájek R, Hungria V, Thompson MA, Cook G, Ojeda JV, Weisel KC, Berdeja JG, Usmani SZ, Symeonidis A, Nascimento-Ferreira I, Arthur D, Mokrá L, Ren K, Cherepanov D, Terpos E
Eur J Haematol
· 2026 Apr · PMID 41528195
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OBJECTIVES: To assess the effectiveness/safety of three proteasome inhibitors (PIs), plus lenalidomide-dexamethasone (Rd) triplet regimens, for the treatment of relapsed/refractory multiple myeloma (RRMM) in a real-world...OBJECTIVES: To assess the effectiveness/safety of three proteasome inhibitors (PIs), plus lenalidomide-dexamethasone (Rd) triplet regimens, for the treatment of relapsed/refractory multiple myeloma (RRMM) in a real-world setting, using data from the observational INSIGHT-MM study (NCT02761187). METHODS: Adults with RRMM who received ixazomib, carfilzomib, or bortezomib plus Rd (IRd, KRd, or VRd, respectively) in the second or later line of therapy (LoT) were included. Patient characteristics, response to therapy (Kaplan-Meier analysis), and safety were reported descriptively. Multivariable Cox proportional hazards models were used to assess comparative effectiveness between regimens, whilst adjusting for cohort imbalances. RESULTS: Overall, 356 LoTs (IRd n = 181; KRd n = 96; VRd n = 79) from 348 patients were included. There was heterogeneity in patient characteristics between cohorts. Median real-world progression-free survival (rwPFS) for IRd, KRd, and VRd was 14.5, 13.2, and 9.1 months, respectively. After adjustment for baseline covariates, no significant differences in rwPFS were observed between regimens. All three regimens demonstrated a manageable safety profile. CONCLUSIONS: IRd, KRd, and VRd demonstrated comparable effectiveness and safety for the treatment of RRMM in a real-world setting, highlighting the need for a holistic evaluation of individual patients' needs and circumstances when selecting an appropriate PI. CLINICAL REGISTRATION: Clinical trial registration for the INSIGHT-MM study: NCT02761187; https://clinicaltrials.gov/study/NCT02761187.
Johnson M, Cai Y, Vasconcelos AG
… +10 more, Orchard P, Auer PL, Lettre G, Wen J, Franceschini N, Kooperberg C, Sun W, Hsu L, Raffield LM, Reiner AP
Eur J Haematol
· 2026 May · PMID 41528117
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Sickle cell trait (SCT) is the heterozygous carrier state for the HBB missense variant which causes sickle cell disease (SCD). SCT has been associated with increased risk of venous thromboembolism and chronic kidney dise...Sickle cell trait (SCT) is the heterozygous carrier state for the HBB missense variant which causes sickle cell disease (SCD). SCT has been associated with increased risk of venous thromboembolism and chronic kidney disease as well as alterations in clinical laboratory parameters. To investigate differential gene expression in SCT, we used RNA sequencing of whole blood samples collected from 805 African American female participants (143 SCT; 660 controls) from the Women's Health Initiative Long Life Study (mean age = 76). We identified 226 differentially expressed genes (DEGs) in SCT compared to non-carriers (FDR < 0.05). Enriched pathways included those related to erythropoiesis, hemoglobin synthesis, and proteasomal degradation. Many of the SCT-associated DEGs were previously reported as differentially expressed in blood from individuals with SCD. Among the DEGs associated with SCT, we observed enrichment of upregulated ubiquitin-related genes normally downregulated during the later stages of erythroid differentiation, a pattern previously reported in SCD. Several of the SCT-associated DEGs highlight mechanisms that potentially link hemolysis or erythropoiesis to hypoxic kidney tubular injury. Future investigation of these genes using single cell transcriptomic analysis in relevant tissues may be useful in understanding mechanisms for adverse health outcomes in individuals with SCT.
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...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.
Several adaptations have been reported since the introduction of posttransplant cyclophosphamide (PTCy)-based haploidentical transplantation (Haplo). This single-center observational study compared the outcomes of PTCy-b...Several adaptations have been reported since the introduction of posttransplant cyclophosphamide (PTCy)-based haploidentical transplantation (Haplo). This single-center observational study compared the outcomes of PTCy-based Haplo with MMF at 30 mg/kg to a concurrent cohort of unrelated donors (URD) who received mainly ATG at 6 mg/kg proximal to transplantation. We included 174 patients (median follow-up: 33 months). Two-year OS for Haplo was 55%, which was not significantly lower than that for URD (67%, p = 0.22). Two-year RFS was 53% for Haplo, compared to 60% for URD (p = 0.31). Two-year GRFS was significantly worse for Haplo (24%) compared to URD (40%, p < 0.01). Relapse rates were similar (16% for Haplo and 21% for URD, p = 0.66), but non-relapse mortality was significantly higher for Haplo (31%) versus 19% for URD (p = 0.04). GVHD outcomes did not differ in univariable analyses. In multivariable analyses, there was a trend toward higher grades III-IV aGVHD (HR = 2.01, p = 0.08) and moderate to severe cGVHD (HR = 1.80, p = 0.05). In summary, we have shown that MMF at 30 mg/kg in Haplo transplants achieved similar PFS and OS compared to ATG-based URD. However, GRFS was lower, likely due to a significantly higher NRM associated with a trend towards higher moderate to severe cGVHD.
García-Cadenas I, Guerreiro M, Yañez L
… +21 more, Chorao P, Martin F, Suárez-Lledó M, Pérez A, Tomás LG, López J, Marsal J, Romero N, Huguet M, Zabalza A, González-Vicent M, Vázquez L, Silva P, Gil D, Micó-Cerdà M, Sánchez P, Filaferro S, Balsalobre P, Jiménez-Ubieto A, Martino R, Piñana JL
BACKGROUND: Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (EBV + PTLD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Given evolving transplantat...BACKGROUND: Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (EBV + PTLD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Given evolving transplantation practices, updated data are needed. OBJECTIVE: Multicenter analysis of PTLD epidemiology, clinical characteristics, and outcomes in Spain. METHODS: Retrospective study across 17 Spanish transplant centers including all proven/probable EBV+ PTLD cases after allo-SCT from January 2000 to June 2023. RESULTS: Among 14.568 allo-SCTs, 170 PTLD cases were identified (1.2%) peaking in 2010-2017 (2.0%), versus 0.9% in 2000-2009 and 0.7% in 2018-2023. Median onset was 91 days; 75% occurred within 6 months. Proven cases comprised 67%, mostly diffuse large B-cell lymphoma. Advanced stage occurred in 67%, extranodal disease in 22%. Rituximab ± immunosuppression reduction (ISR) was given to 80%, yielding a 62.4% response rate. Responders had superior survival (2-year OS 73.4% vs. 10.7%). EBV-specific cellular therapies were infrequently used. Median follow-up was 97.8 months; 5-year OS 39.6%, with PTLD causing 49% of deaths. Severe hypoalbuminemia, lack of ISR, and rituximab refractoriness predicted worse survival. CONCLUSIONS: EBV + PTLD frequency has declined in Spain. Prognosis remains poor for rituximab non-responders, highlighting limited access to EBV-specific cellular therapies as an unmet need.
Walther D, Ernst J, Wollenhaupt C
… +5 more, Wittig S, Härtel M, Brodt G, Milde T, Gruhn B
Eur J Haematol
· 2026 Apr · PMID 41489018
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This retrospective study evaluates the efficacy and safety of donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) in children. We describe the long-term use of preemptive, prop...This retrospective study evaluates the efficacy and safety of donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) in children. We describe the long-term use of preemptive, prophylactic, and therapeutic DLI with a gradual dose increase in half-log increments. Under close monitoring, we increased the DLI dose only in patients that did not show signs of graft-versus-host disease (GVHD). In the preemptive cohort, 10 of 12 patients (83%) with minimal residual disease (MRD) positivity remained relapse-free. Among 11 patients with genetic diseases and mixed chimerism, nine (82%) responded to preemptive DLI. Six patients (100%) of the prophylactic cohort with a very high risk of relapse had a successful outcome without relapse or GVHD. Three of the five patients (60%) of the therapeutic cohort were successfully treated with DLI. We observed acute GVHD (grade I and II) in only two patients (6%). The results of our study indicate that the long-term use of DLI is a promising strategy and can effectively prevent relapse, graft rejection, and even cure relapse. The observed low rate of GVHD may be attributed to the gradual dose increase. Therefore, we consider DLI a safe and effective therapeutic option.
Ozelo MC, Luciani M, Glosli H
… +11 more, Kavakli K, Samji N, Makris GC, Tueckmantel C, Maas Enriquez M, Oliveira LC, Gupta S, Arbesú MG, Davoli M, Chan AKC, Mancuso ME
Eur J Haematol
· 2026 Apr · PMID 41486550
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BACKGROUND: In the earlier PROTECT VIII Kids study (NCT01775618), damoctocog alfa pegol was efficacious for prevention and treatment of bleeds in children aged < 12 years with severe haemophilia A. OBJECTIVE: Assess the...BACKGROUND: In the earlier PROTECT VIII Kids study (NCT01775618), damoctocog alfa pegol was efficacious for prevention and treatment of bleeds in children aged < 12 years with severe haemophilia A. OBJECTIVE: Assess the safety of damoctocog alfa pegol, including hypersensitivity and loss of efficacy (LoE) due to an immune response to polyethylene glycol, in children aged 7 to < 12 years with severe haemophilia A. METHODS: Alfa-PROTECT is a phase 3, multicentre, open-label, single-arm study (NCT05147662). Primary endpoint was the incidence of adverse events of special interest (AESI) leading to discontinuation during the first 4 exposure days. RESULTS: Overall, 35 children enrolled; 32 completed the 6-month study, 21 (60%) reported ≥ 1 AE. Median (range) treatment duration was 182 (172-198) days. All AEs were mild/moderate; 3/35 children (8.6%) had study drug-related AEs. One (2.9%) LoE event was considered an AESI, and led to temporary treatment interruption. No AEs resulted in study drug discontinuation. The probability of < 5% of patients experiencing an AESI was 92.2%. Bleed protection was maintained with damoctocog alfa pegol prophylaxis. CONCLUSIONS: These data confirm the safety profile of damoctocog alfa pegol in children aged 7 to < 12 years with severe haemophilia A. Secondary endpoints indicate treatment was efficacious. TRIAL REGISTRATION: The Alfa-PROTECT trial is registered at ClinicalTrial.gov (NCT05147662).
Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for various pediatric diseases. In this study, we analyzed 52 pediatric patients undergoing allogeneic HSCT to determine how the content of myeloid a...Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for various pediatric diseases. In this study, we analyzed 52 pediatric patients undergoing allogeneic HSCT to determine how the content of myeloid and lymphoid CD34 progenitor cells, as well as HMOX1 promoter polymorphisms, affects neutrophil (NE) and platelet engraftment (PE). We found that NE was significantly accelerated in patients who received a higher dose of CD34 myeloid cells (> 4 × 10/kg), while lymphoid progenitors had no impact on engraftment. PE was not affected by any CD34 cell subtype. Moreover, in a subset of 28 patients, the presence of short HMOX1 promoter alleles in recipients, but not in donors, was associated with delayed NE, particularly during early post-transplantation. These results highlight the importance of graft composition-specifically myeloid CD34 cell dose-and recipient HMOX1 genotype in determining the kinetics of neutrophil recovery. This may offer a new perspective for graft optimization and potential use of HO-1-targeted therapies to enhance engraftment.