Search Results (2,121)

Background: As hyperbaric oxygen therapy has been sporadically used in combination with antimicrobial treatment for refractory infections in patients with hematologic malignancies, data on its efficacy and outcomes are limited. Methods: We retrospectively analyzed 55 patients with hematologic malignancies treated with hyperbaric oxygen therapy over a 10-year period at a single tertiary care center and report on patients’ clinical features, infection types, treatment responses, and survival outcomes. Results: The most common underlying hematologic malignancy diagnosis was acute myeloid leukemia (30 patients, 55%). The most common hyperbaric oxygen therapy indications were invasive mold disease (IMD) (35 patients, 64%), BK virus-associated cystitis (17 patients, 31%), and bacterial cellulitis (3 patients, 5%). Patients underwent a median of 10 hyperbaric oxygen therapy sessions (range, 1–45). In total, 54 (98%) of the 55 patients were evaluable for response, of whom 32 (59%) patients demonstrated a response, defined as either resolution or stabilization of the infection. Among the 35 patients with IMDs, we found that 11 patients (31%) achieved a complete response, 5 (14%) had a partial response, 6 (17%) had stable disease, and 13 (37%) patients experienced progression of their infection. In contrast, among the 17 patients with BK virus-associated cystitis, 9 patients (53%) had persistent or worsening hematuria. The two evaluable patients with bacterial cellulitis responded with resolution of the infection. We reviewed the status of the hematologic malignancies at the time of hyperbaric oxygen therapy treatment and found that the 21 patients whose hematologic malignancies were in remission tended to have a higher response rate of their infection compared to patients whose hematologic malignancies were not in remission (73% vs. 46% p = 0.057). Despite the response of infections, 1-year mortality in these patients remained high at 76%. Conclusions: Based on our experience, hyperbaric oxygen therapy, in conjunction with appropriate anti-infective therapy and debridement surgery, could benefit selected patients with hematologic malignancies, especially those whose underlying disease is controlled but experience recalcitrant bacterial or fungal infections. Full article

Survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL) are at risk of developing long-term adverse effects after survival. This study examined observed proportions of perceived mental distress, fatigue, and executive function (EF) impairment in adult childhood cancer survivors (CCSs) of ALL, AML, and NHL. Secondly, it examined the association between perceived EF impairment and mental distress or fatigue. Participants (n = 132; 57% female) were recruited from two major Norwegian hospitals. Self-report questionnaires included the Behavior Rating Inventory of Executive Function, Adult Version, the Hopkins Symptom Checklist-25, and the Fatigue Severity Scale. Proportions exceeding established clinical thresholds were calculated, and groups were compared using Pearson’s chi-squared test and Newcombe confidence intervals. Overall, 49% and 41% of participants met the clinical thresholds for depression and anxiety; 43% for fatigue; and 28% for EF impairment. Perceived EF impairment was significantly associated with mental distress and fatigue. Mental distress, fatigue, and EF impairment are commonly reported and distressing late effects among CCSs of ALL, AML, and NHL. Follow-up care focusing on neurocognitive and psychological outcomes is important for the long-term functioning and well-being of this survivor group. Targeted neurocognitive rehabilitation may represent a key component of follow-up care. Full article

Background/Objectives: Myelodysplastic syndromes (MDS) carry a highly variable prognosis, stratified by the Revised International Prognostic Scoring System (IPSS-R) and the Molecular IPSS (IPSS-M). CEBPA mutations define a favorable-risk subgroup in acute myeloid leukemia (AML), yet their prognostic significance in MDS has not been characterized. Methods: We analyzed 2442 patients from the International Working Group (IWG) 2022 multi-center MDS registry after pre-specified exclusions. Overall survival (OS) and leukemia-free survival (LFS) were compared between CEBPA-mutated (n = 66; 2.7%) and wild-type patients using Kaplan–Meier estimation and Cox proportional hazards regression, adjusting for age, sex, and IPSS-R score; pre-specified subgroup, sensitivity, competing-risk, and mutation subtype analyses were performed. Results:CEBPA-mutated patients had markedly inferior OS (median 17.2 versus 42.2 months; HR 2.05, 95% CI 1.50–2.79; p < 0.001). After IPSS-R adjustment, the hazard ratio remained adverse (HR 1.39, 95% CI 1.00–1.94; p = 0.053), with uniform directionality across all 13 evaluable subgroups and no significant interaction. Co-mutation adjustment for ASXL1 and STAG2 further attenuated the hazard ratio to HR 1.11 (95% CI 0.79–1.57; p = 0.54), suggesting part of the observed signal reflects co-mutation burden rather than an independent CEBPA effect. Competing-risk analysis suggested that the excess mortality is mediated through AML transformation (CEBPA-mutated versus wild-type subdistribution hazard ratio of 1.89, 95% CI 1.20–2.99; p = 0.006) rather than non-transformative MDS mortality (cause-specific HR 0.97; p = 0.890). Truncating mutations drove the adverse signal (HR 2.21; p = 0.023), while basic leucine zipper (bZIP) domain mutations showed no significant effect (HR 1.25; p = 0.470). Conclusions:CEBPA mutations identify a rare MDS subgroup with markedly inferior survival, driven by truncating loss-of-function mutations and associated with leukemic transformation; the AML-derived bZIP-favorable paradigm does not translate to MDS, and CEBPA mutation status merits a prospective study to assess clinical utility for risk stratification. Full article

Pediatric acute myeloid leukemia (AML) is biologically heterogeneous, and genomic profiling increasingly informs risk stratification and treatment. We evaluated the relationship between induction response, genomic risk, transplant allocation, and survival in pediatric AML. We retrospectively analyzed 38 pediatric patients with newly diagnosed AML, treated between 2020 and 2025. Clinical, cytogenetic, molecular, treatment, and outcome data were collected. Genomic alterations were assessed using cytogenetics, fluorescence in situ hybridization (FISH), molecular testing, and next-generation sequencing (NGS). Survival was estimated by Kaplan–Meier analysis, and prognostic factors for event-free survival (EFS) were assessed using univariable Cox regression. This study is exploratory given the limited sample size and should be interpreted accordingly. Complete remission (CR) after the first course of induction was achieved in 25/38 patients (65.8%), partial remission (PR) in 3/38 (7.9%), and refractory disease in 10/38 (26.3%). Twenty-four patients underwent allogeneic hematopoietic stem cell transplantation; 17/24 (70.8%) were alive at last follow-up, with a 2-year overall survival rate of 72.9%. Both induction response and genomic risk stratification showed suggestive associations with outcome; descriptively, induction response showed the strongest prognostic discrimination, with achievement of CR associated with markedly improved survival. High cytogenetic risk and FLT3-ITD were significantly associated with inferior EFS. Post-induction measurable residual disease (MRD) positivity was detected in 16 of 38 patients (42.1%) and was associated with suboptimal induction response; MRD negativity did not uniformly preclude adverse outcomes, particularly in the high-risk genomic subgroup. Genomic profiling refined biological risk and post-remission treatment allocation. Integrated assessment of genomic risk, induction response, and MRD status may improve therapeutic stratification in pediatric AML. Full article

Acute myeloid leukemia (AML) is one of the most common types of hematological malignancies and a leading cause of cancer deaths. It is characterized by the rapid accumulation of typically immature myeloid cells that serve to disrupt the production of mature cells, leading to a range of clinical sequelae. The role of recurrent chromosomal aberrations has long been appreciated in this disease, but a myriad of gene mutations have been increasingly acknowledged as having important roles. This review provides a comprehensive overview of the mutational landscape of AML, discussing the various genetic lesions in terms of their function, classification, etiological role, prognostic value, therapeutic impact, detection, and monitoring, with a particular focus on gene mutations. Full article

Background: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. Objectives: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-organ toxicity, to characterize their mechanisms of action and organ targets, and to identify evidence gaps and agents with translational potential. Methods: The review was designed and reported in accordance with the PRISMA-ScR checklist. A structured electronic search was conducted across PubMed/MEDLINE, Scopus, Cochrane Library and Embase, and Web of Science from database inception to 15 July 2025. Eligible studies were restricted to full-text, peer-reviewed, English-language research involving in vivo mammalian models administered cytarabine as the principal toxin, with at least one pharmacological co-intervention and at least one quantitative or histopathological organ-injury outcome. Results: From 5701 retrieved records, 36 eligible in vivo mammalian studies (spanning 1964–2024) were identified. Included studies addressed neurotoxicity (n = 6), gastrointestinal mucositis (n = 9), ocular toxicity (n = 3), hepatotoxicity (n = 3), bone marrow suppression (n = 4), chemotherapy-induced alopecia (n = 5), and reproductive and developmental toxicity (n = 4). Five recurring mechanistic strategies were identified across the heterogeneous agents tested: redox buffering (N-acetylcysteine, α-lipoic acid, rutin, swertiamarin, α-tocopherol), mitochondrial preservation (betanin, thymoquinone, vitamin D, sodium zinc dihydrolipoylhistidinate [DHLHZn]), tissue-microenvironment reprogramming (apraglutide, BADGE, plerixafor, short-chain fatty acids, β-glucan), molecular antagonism (deoxycytidine, dCMP), and immunomodulation (lienal peptide, IL-1β, AHCC). Conclusions: This scoping review provides the first systematic cartography of pharmacological mitigation strategies for cytarabine-induced multi-organ toxicity. Five mechanistic pathways converge across eight organ systems, with apraglutide and N-acetylcysteine representing the most clinically translatable candidates. Plerixafor and PPARγ blockade by BADGE constitute high-priority candidates for bone marrow niche protection, while the deoxycytidine antagonism principle warrants formal pharmacokinetic evaluation. The complete absence of cardiotoxicity mitigation data defines the most critical gap for future research. Full article

Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery. Full article

Acute myeloid leukemia (AML) is a biologically heterogeneous malignancy in which therapeutic decision-making is increasingly guided by molecular and immunophenotypic diagnostics. Advances in genomic profiling and risk stratification have enabled the integration of targeted agents into frontline and relapsed/refractory treatment strategies. Among these, midostaurin, venetoclax, and gemtuzumab ozogamicin represent paradigm-shifting therapies whose clinical benefit depends on accurate and timely diagnosis. This review examines the diagnostic frameworks that inform the use of these agents and discusses their incorporation into contemporary AML management. Midostaurin has demonstrated improved outcomes in patients with FLT3-mutated AML when combined with intensive chemotherapy, underscoring the importance of early molecular testing. Venetoclax, a BCL-2 inhibitor, has expanded therapeutic options for older or unfit patients when used with hypomethylating agents or low-dose cytarabine, with emerging evidence linking response to cytogenetic and molecular features. Gemtuzumab ozogamicin, an anti-CD33 antibody–drug conjugate, illustrates the clinical relevance of immunophenotypic assessment and risk-adapted dosing strategies. We highlight current evidence supporting diagnosis-driven therapy selection, practical considerations for clinical implementation, and ongoing challenges, including resistance mechanisms and optimal sequencing. Integrating precise diagnostic tools with targeted therapies represents a critical step toward personalized AML care and improved patient outcomes. Full article

Background: Multiparameter flow cytometry is widely used in the diagnosis of acute leukemia, allowing for rapid identification of leukemic cells based on their immunophenotype. The EuroFlow Acute Leukemia Orientation Tube was designed as a standardized screening tool to support early diagnostic orientation and guide further, more targeted testing. In this study, we assessed the diagnostic performance of the ALOT panel in pediatric patients with suspected acute leukemia. Methods: A total of 254 pediatric patients (0–18 years) with suspected acute leukemia were analyzed. Bone marrow samples were assessed using multiparameter flow cytometry with the EuroFlow ALOT panel, comprising eight markers (MPO, cyCD79a, CD34, CD19, CD3, cyCD3, CD7, and CD45). Final diagnoses were established using extended immunophenotypic panels and additional diagnostic methods when required. Samples were processed according to EuroFlow standard operating procedures and acquired on FACSCanto II and FACSCanto 10-color flow cytometers (BD Biosciences). Diagnostic performance was assessed by calculating sensitivity, specificity, precision, accuracy, and negative predictive value. Results: Among 254 patients, 234 were diagnosed with hematologic disorders, while 20 had normal bone marrow findings. The ALOT panel correctly identified all pathological samples and did not misclassify any normal sample, resulting in 100% sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for discrimination between abnormal and normal samples. In terms of exact diagnostic orientation, ALOT correctly classified 244 of 254 cases (96.1%) using a single-tube approach. The remaining 10 cases (3.9%), including rare entities such as Burkitt leukemia, chronic myeloid leukemia, and transient myeloproliferative syndrome, required extended immunophenotypic evaluation. Importantly, these cases were not false negative results, as all were correctly identified as abnormal. Conclusions: The EuroFlow ALOT panel is a reliable screening tool for rapid diagnostic orientation in pediatric acute leukemia. Its implementation facilitates targeted selection of extended immunophenotypic panels, improving the efficiency and cost-effectiveness of diagnostic workflows. Full article

Growth hormone-releasing hormone (GHRH) antagonists have displayed anti-neoplastic activity against a multitude of cancers in vitro, as well as in vivo, via xenografted tumors in nude mice. Following a successful demonstration of GHRH antagonists treating non-Hodgkin’s lymphoma and the discovery of GHRH mRNA and peptide products in immune cells, GHRH antagonism was explored in acute myeloid leukemia (AML), a disease characterized by a malignant expansion of immature myeloid progenitors, and poor 5-year survival. Targeted therapies have yielded breakthroughs in treatment response and overall survival, such as all-trans retinoic acid/arsenic trioxide (ATRA/ATO) for acute promyelocytic leukemia (APL), or FLT3 inhibitors, IDH inhibitors, and menin inhibitors for AML harboring actionable genetic lesions. However, therapeutic resistance remains a major barrier to durable remission. GHRH receptor (GHRH-R) has been reported in several experimental models of AML, including drug-resistant sublines. Significant time- and dose-dependent reduction in leukemic growth was observed in vitro and in vivo following MIA-602 treatment. FLT3 inhibitor resistance has been associated with activation of PI3K/AKT, ERK/MAPK, inflammatory, stromal, and apoptotic escape pathways. The documented effects of GHRH-R antagonism raise the possibility that it could influence signaling networks relevant to therapeutic resistance in AML. This hypothesis remains speculative; to date no studies have stratified AML by FLT3 status in the context of GHRH-R expression or GHRH antagonism, and there is currently no evidence that MIA-602 directly alters FLT3 receptor signaling or inhibitor sensitivity. Full article

The management of acute myeloid leukemia (AML) remains characterized by high relapse rates despite advances in induction and consolidation therapy. Relapse prevention represents a major unmet need, particularly in patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT) or at high risk of post-transplant recurrence. This review examines current evidence supporting maintenance strategies following intensive chemotherapy or allo-HSCT, with emphasis on measurable residual disease (MRD)-guided approaches and targeted therapies. We summarize data from randomized and phase II/III trials evaluating hypomethylating agents, FLT3 inhibitors, IDH inhibitors, and immunotherapeutic strategies in post-remission settings. Oral azacitidine (CC-486) demonstrated overall survival benefit in older patients in first complete remission who were not transplant candidates, establishing a standard of care in this population. In FLT3-mutated AML, post-transplant maintenance with sorafenib and gilteritinib reduces relapse risk, with emerging evidence supporting MRD as a predictive biomarker for benefit. Other targeted agents and immunotherapies have shown promising early-phase results, although confirmatory data are limited. Ongoing phase III studies will clarify optimal patient selection, treatment duration, and integration with transplantation, aiming to transform post-remission management from passive surveillance to precision-based relapse prevention. Full article

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes in relapsed or refractory hematologic malignancies, but long-term cognitive outcomes remain poorly understood. We compared the incidence and time course of cognitive impairment and associated neurological complications after CAR-T therapy compared with autologous stem cell transplantation (ASCT). Methods: This retrospective, propensity-matched cohort study utilized the TriNetX US Collaborative Network (January 2014–April 2025). To ensure concurrent comparisons, ASCT recipients were restricted to an index date beginning in August 2017 or later. CAR-T recipients were matched 1:1 to ASCT recipients for demographics, disease, comorbidities, prior and concomitant treatments, and laboratory parameters. The primary endpoint was time to cognitive impairment, as defined by ICD-10 codes. Results: After comparing 3067 CAR-T patients (median follow-up 634 days) with 3067 ASCT patients (median follow-up 713 days), CAR-T recipients had a higher risk of cognitive impairment (HR 1.58; 95% CI 1.39–1.80; p < 0.001). Because the risks were not proportional (Schaenfeld p < 0.001), the difference was also expressed as restricted median survival time (RMST): CAR-T recipients spent approximately 25 and 53 days fewer days without cognitive impairment at 1 and 2 years, respectively (both p < 0.001). The risk was greatest at 30 days (HR 4.22; 95% CI 3.23–5.53), but remained elevated in control analyses at 30 and 90 days that excluded the acute ICANS window (HR 1.30 and 1.25, respectively; both p < 0.05). Neurological dysfunction, particularly encephalopathy (HR 2.04; 95% CI 1.73–2.40), was more common after CAR-T. Conversely, CAR-T was associated with a reduced risk of secondary acute myeloid leukemia (HR 0.46; 95% CI 0.38–0.55; p < 0.001). Conclusions: CAR-T therapy is associated with a higher risk of cognitive impairment that persists beyond the acute phase. As these are observational, code-based data, they should be interpreted as associations rather than evidence of a specific mechanism, and they highlight the need for informed consent discussions, long-term neurocognitive monitoring, and the development of neuroprotective strategies. Full article

We previously showed that TCEA1 deficiency in myeloid cells promotes proliferation, impairs differentiation and inhibits apoptosis, but its role and underlying mechanism in acute myeloid leukemia (AML) are unknown. Here, in NB-4 cells, an M3 subtype of AML, TCEA1 overexpression suppressed proliferation (p < 0.001), induced S-phase arrest (from 35.35% to 19.47%, p < 0.001), increased apoptosis (from 10.37% to 23.5%, p < 0.001), and promoted differentiation. Mechanistically, TCEA1 overexpression upregulated C/EBPε and IRF8 at the mRNA and protein levels; conversely, TCEA1 knockdown downregulated both. Rescue experiments in TCEA1 knockdown 32Dcl3 cells showed that ectopic C/EBPε or IRF8 reversed the uncontrolled proliferation, blocked apoptosis, and impaired differentiation. In xenograft mouse models, TCEA1 overexpression reduced leukemic infiltration in the bone marrow, spleen, and liver; extended overall survival; and elevated C/EBPε and IRF8 expression in vivo. Analysis of public APL datasets revealed that high TCEA1 expression is associated with a favorable prognosis (HR = 0.43, 95% CI: 0.2–0.93, logrank p = 0.028). Collectively, our findings demonstrate that TCEA1 suppresses proliferation, promotes apoptosis and differentiation, and attenuates disease progression by upregulating C/EBPε and IRF8, positioning this regulatory mechanism as a potential therapeutic target and prognostic biomarker for this disease. Full article

To investigate the predictive factors for resistance to VEN combined with HMAs in the treatment of AML, construct a drug resistance prediction model, and visualize the model. A retrospective analysis was conducted on 74 AML patients. Multivariate logistic regression was used to identify independent predictors of primary resistance, based on which a nomogram model and a risk scoring system for drug resistance were constructed. The results showed that KIT (p = 0.012), TP53 (p = 0.010), and FAB-M5 (p = 0.059) were significantly associated with primary resistance to VEN. A nomogram prediction model incorporating FAB-M5, KIT, and TP53 was established. Based on the nomogram model, a drug resistance prediction scoring tool comprising three variables was developed, categorizing patients into high-risk (6–10 points), intermediate-risk (3–5 points), and low-risk (0–2 points) groups. Significant differences in NR rates were observed among the three risk groups (p < 0.001). KIT, TP53, and FAB-M5 are independent factors influencing VEN resistance. The constructed nomogram prediction model and scoring system may provide valuable references for predicting primary resistance to VEN. Full article

Acute myeloid leukemia (AML) presents significant challenges for CAR T-cell therapy due to its pronounced heterogeneity and the lack of leukemia-specific surface antigens. Frequently targeted antigens, such as CD33, CD123, and CLL-1, are also present on normal hematopoietic progenitors, resulting in on-target, off-tumor toxicity and restricting clinical translation. To address these challenges, logic-gated CAR T-cell strategies have been developed to enable combinatorial antigen recognition. These approaches incorporate engineered circuits, including AND, OR, and NOT gates, as well as synNotch receptors, split-CAR configurations, and inhibitory platforms (iCARs and Tmod), to improve discrimination between leukemic and normal cells. In AML, CAR T-cell efficacy and persistence are further affected by the immunosuppressive bone marrow and lymphoid microenvironment, which involves immune cell trafficking, cytokine signaling, and lymphatic immune regulation. Preclinical studies employing dual-target strategies, such as CD33/CD123 and CLL-1/CD123, have shown improved antileukemic efficacy with reduced hematopoietic toxicity. This review summarizes the molecular principles underlying logic-gated CAR-T systems and examines their translational application in AML. Additionally, it highlights emerging evidence connecting the regulation of lymphatic and immune microenvironments to CAR T-cell persistence, trafficking, and toxicity and discusses future strategies, such as single-cell antigen mapping, computational circuit engineering, and synthetic immune programming, to enhance the precision and clinical feasibility of next-generation AML immunotherapies. Full article